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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation R192G

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 11 clinical trials

Clinical Trials


1 Safety and Immunogenicity of Oral Microencapsulated CS6 Vaccine and LT(R192G) Adjuvant in Volunteers

The study will enroll approximately 60 volunteers. The vaccine is given as a drink in flavored soda water. Volunteers will either receive a 3-dose vaccination with doses spaced two weeks apart or a 4-dose vaccination with doses spaced 2 days apart depending upon their availability for follow-up. Once assigned to a vaccination schedule, volunteers will be randomly assigned to receive the meCS6 vaccine with or without the mLT adjuvant for all vaccine doses. Neither the study investigators nor the volunteers will know which group they are assigned. Volunteers will be asked to be available for clinic visits and telephone follow-ups during the study period and provide blood and stool specimens for testing.

NCT00090688
Conditions
  1. Diarrhea
Interventions
  1. Biological: meCS6 + LT(R192G)
MeSH:Diarrhea
HPO:Diarrhea

Safety and Immunogenicity of Oral Microencapsulated CS6 Vaccine and LT(R192G) Adjuvant in Volunteers. --- R192G ---

Phase 1 meCS6 + LT(R192G) Vaccine Study The study will enroll approximately 60 volunteers. --- R192G ---

Inclusion Criteria: - Available for required follow-up period - Women must have a negative pregnancy test - Women must not to try to become pregnant while on study and for 2 months after study is completed Exclusion Criteria: - History of travellers' diarrhea - Occupation that involves handling of E. coli or cholera bacteria, or E. coli vaccine - Regular use of anti-diarrheal, anti-constipation, or antacid therapy - Abnormal bowel habits - Pregnant or nursing women - History of chronic gastrointestinal illness or major gastrointestinal surgery - Allergies to vaccines - Positive HIV, Hepatitis B or Hepatitis C tests - Regular use of oral steroid medication - Clinically significant abnormalities on physical examination Inclusion Criteria: - Available for required follow-up period - Women must have a negative pregnancy test - Women must not to try to become pregnant while on study and for 2 months after study is completed Exclusion Criteria: - History of travellers' diarrhea - Occupation that involves handling of E. coli or cholera bacteria, or E. coli vaccine - Regular use of anti-diarrheal, anti-constipation, or antacid therapy - Abnormal bowel habits - Pregnant or nursing women - History of chronic gastrointestinal illness or major gastrointestinal surgery - Allergies to vaccines - Positive HIV, Hepatitis B or Hepatitis C tests - Regular use of oral steroid medication - Clinically significant abnormalities on physical examination Diarrhea Diarrhea The Phase 1 section of this study is a randomized double blind trial in which a total of 60 subjects (minimum of 52 allowable) will receive on of two oral vaccine doses according to the following chart: Group Subset N CS6(Encapsulated) LT(R192G) I A 15 0.95mg 2 micrograms II B 15 0.95mg -- III A 15 0.95mg 2 micrograms IV B 15 0.95mg -- *minimum of 13 volunteers/group Volunteers in Group I will receive three immunizations (study days 0, 14, and 28) during the vaccine series. --- R192G ---

Primary Outcomes

Measure: Safety

Measure: Mucosal Immunogenicity

Measure: Systemic Immunogenicity

2 A Randomized, Observer-Blind, Placebo-Controlled Study to Assess the Safety and Immunogenicity of Intramuscular Inactivated Influenza A/H5N1 Vaccine Administered With and Without an Adjuvant Patch in Healthy Adults

This is a Phase 1/2, randomized, observer-blind, placebo-controlled clinical trial. A maximum of 500 eligible subjects in 10 groups will be enrolled, randomized and vaccinated in this study. Subjects will receive an intramuscular injection of either the influenza A/H5N1 (low, medium or high dose) or placebo on Day 0 and Day 21 with or without a patch. This study will be performed in two parts. In Part 1, an initial safety evaluation will be performed in 100 randomized subjects. A Safety Review Committee (SRC)will review all safety data, including laboratory values, through the Day 7 visit, and compare those data against Stopping Criteria. If the treatments are considered safe, Part 2 of the study will be initiated and a second vaccination will be administered to subjects in Part 1 on Day 21. In Part 2, the remaining 400 subjects will be randomized, treated, and will follow the same visit structure and protocol-defined requirements as subjects in Part 1, without the additional laboratory safety measurements. An SRC review will also be performed of all safety data through the Day 28 visit for subjects participating in Part 1.

NCT00532792
Conditions
  1. Pandemic Influenza
Interventions
  1. Biological: A/H5N1
  2. Biological: A/H5N1
  3. Biological: A/H5N1
  4. Biological: A/H5N1
  5. Biological: A/H5N1
  6. Biological: A/H5N1
  7. Biological: A/H5N1
  8. Biological: A/H5N1
  9. Biological: A/H5N1
  10. Biological: Placebo
MeSH:Influenza, Human Influenza in Birds

Acceptable forms of birth control are: abstinence, hormonal contraceptives (oral, injectable, implant, patch, ring), double-barrier contraceptives (condom or diaphragm, with spermicide), and IUD Exclusion Criteria: - Laboratory abnormalities [as determined by the Toxicity Grading Scale (grade 1 4)] at laboratory screening - Abnormalities at physical examination [as determined by the Toxicity Grading Scale (grade 1-4)] - Known allergies to any component of the vaccine - Known egg protein allergy - Known allergies to adhesives - Known disturbance of coagulation - Participated in research involving investigational product within 45 days before planned date of first vaccination - Donated or received blood or blood products such as plasma within the past 45 days - Received any licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to planned date of first vaccination - Ever received investigational enterotoxigenic E. coli, LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd - Ever received cholera toxin or vaccine (e.g. --- R192G ---

Primary Outcomes

Measure: Safety of Intramuscular A/H5N1 with and without the LT adjuvant patch

Time: 6 months

Secondary Outcomes

Measure: Demonstration of adjuvant effect and evaluation of immunogenicity

Time: Day 42

3 A Phase 2, Randomized, Open-Label Study to Compare the Immunogenicity and Safety of a Self-Administered LT Vaccine Patch With an LT Vaccine Patch Administered by a Clinician

To evaluate the immune responses achieved following self-administered heat-labile enterotoxin of E. coli (LT) vaccination by transcutaneous immunization compared to the immune responses achieved by clinician-administered vaccination.

NCT00565461
Conditions
  1. Pre
  2. Prevention of Travelers' Diarrhea
Interventions
  1. Biological: heat-labile enterotoxin of E. coli (LT)
MeSH:Diarrhea
HPO:Diarrhea

Exclusion Criteria: Subjects meeting any of the following criteria are not eligible for participation in the study: - Laboratory abnormalities [as determined by the Toxicity Grading Scale (grade 1-4)] at laboratory screening - Abnormalities at physical examination [as determined by the Toxicity Grading Scale (grade 1-4)] - Known allergies to any component of the vaccine - Known allergies to adhesives - Participated in research involving investigational product within 30 days before planned date of first vaccination - Donated blood or blood products such as plasma within the past 30 days - Ever received investigational enterotoxigenic E. coli, LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd - Ever received cholera toxin or vaccine (e.g. --- R192G ---

Primary Outcomes

Description: The primary endpoint of this trial was to compare the immunogenicity (i.e., GMTs, GMFRs and seroconversion rates for LT IgG and IgA) of subject self-administered [second] vaccination with clinician-administered [second] vaccination, using the deltoid/thigh (Vaccination 1/Vaccination 2) treatment regimen. GMT: geometric mean titer

Measure: GMTs After a Self-administered LT Vaccine Patch (In-clinic or Away From Clinic) Compared to a Clinician-administered LT Vaccine Patch.

Time: Day 0, Day 14, Day 21, Day 28, Day 35, Day 194

Description: The primary endpoint of this trial was to compare the immunogenicity (i.e., GMTs, GMFRs and seroconversion rates for LT IgG and IgA) of subject self-administered [second] vaccination with clinician-administered [second] vaccination, using the deltoid/thigh (Vaccination 1/Vaccination 2) treatment regimen. GMFR: geometric mean fold ratio GMFRs relative to the baseline titer were determined for LT IgG and LT IgA at each post-baseline time point. All GMFRs were based on log10-transformed data.

Measure: GMFR After a Self-administered LT Vaccine Patch (In-clinic or Away From Clinic) Compared to a Clinician-administered LT Vaccine Patch.

Time: Day 14, Day 21, Day 28, Day 35, Day 194

Description: The primary endpoint of this trial was to compare the immunogenicity (i.e., GMTs, GMFRs and seroconversion rates (SCR) for LT IgG and IgA) of subject self-administered [second] vaccination with clinician-administered [second] vaccination, using the deltoid/thigh (Vaccination 1/Vaccination 2) treatment regimen. seroconversion (SC): two-fold or greater rise in titer relative to Day 0 for LT IgG and a four-fold or greater rise in titer relative to Day 0 for LT IgA

Measure: Seroconversion After a Self-administered LT Vaccine Patch (In-clinic or Away From Clinic) Compared to a Clinician-administered LT Vaccine Patch.

Time: Day 14, Day 21, Day 28, Day 35, Day 194

Secondary Outcomes

Measure: Number of Adverse Events for Self-administered LT Vaccine Patch and Comparison to the Clinician-administered LT Vaccine Patch

Time: 6 months

Measure: Evaluation of Immunogenicity (GMT) for Deltoid/Thigh (Prime/Boost) Versus Deltoid/Deltoid Administered LT Vaccine.

Time: 6 months

Measure: Safety for Self-administration In-clinic Compared to Self-administration Away From the Clinic.

Time: 6 months

Measure: Evaluation of Immunogenicity (GMT) for Self-administration In-clinic Compared to Self-administration Away From the Clinic.

Time: 6 months

Measure: Evaluation of Immunogenicity (GMFR) for Deltoid/Thigh (Prime/Boost) Versus Deltoid/Deltoid Administered LT Vaccine

Time: 6 months

Measure: Evaluation of Immunogenicity (SCR) for Deltoid/Thigh (Prime/Boost) Versus Deltoid/Deltoid Administered LT Vaccine

Time: 6 months

Measure: Evaluation of Immunogenicity (GMFR) for Self-administration In-clinic Compared to Self-administration Away From the Clinic

Time: 6 months

Measure: Evaluation of Immunogenicity (SCR) for Self-administration In-clinic Compared to Self-administration Away From the Clinic

Time: 6 months

4 Randomized, Double-Blinded, Placebo-Controlled, Dose Ranging Study to Assess the Immunogenicity and Safety of LT Application in Healthy Adults

The main purpose of this study is to evaluate the body's immune response to the LT patch at different doses. The secondary purpose of this study is to evaluate the safety of the LT patches at different doses and the safety of the skin preparation system. Another secondary purpose is to compare the safety and the body's immune response to LT patches placed on the upper arm versus the lower back.

NCT00672035
Conditions
  1. Traveler's Diarrhea
Interventions
  1. Biological: Biological: heat-labile enterotoxin of E. coli (LT)
MeSH:Diarrhea
HPO:Diarrhea

- Ever received investigational enterotoxigenic E. coli, LT, or LT(R192G) or NasalFlu, Berna Biotech, Ltd. - Ever received cholera toxin or vaccine (e.g. --- R192G ---

Primary Outcomes

Measure: To evaluate the immunogenicity of LT application at different doses

Time: 6 months

Secondary Outcomes

Measure: To evaluate the safety of LT application at different doses

Time: 6 months

Measure: To evaluate the safety of the skin preparation system

Time: 6 months

Measure: To compare patch performance (safety and immunogenicity) on different anatomical parts of the body

Time: 6 months

5 A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Immunogenicity and Safety of a Two Vaccination Regimen With an LT Vaccine Patch in Healthy Adults

To evaluate and compare the immune responses and safety following a two vaccination regimen by transcutaneous immunization with heat-labile enterotoxin of E. coli (LT) patches or placebo patches.

NCT00751777
Conditions
  1. Prevention of Travelers' Diarrhea
Interventions
  1. Biological: heat-labile enterotoxin of E. coli (LT)
  2. Biological: Placebo
MeSH:Dysentery Diarrhea
HPO:Diarrhea

Exclusion Criteria: - Laboratory abnormalities [as determined by the Toxicity Grading Scale (grade 1 4)] at laboratory screening - Abnormalities at physical examination [as determined by the Toxicity Grading Scale (grade 1-4)] - Known allergies to any component of the vaccine - Known allergies to adhesives - Participated in research involving investigational product within 30 days before planned date of first vaccination or within 90 days after first vaccination - Donated blood or blood products such as plasma within 30 days prior to planned date of first vaccination or within 90 days after first vaccination - Ever received investigational enterotoxigenic E. coli, LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd - Ever received cholera toxin or vaccine (e.g. --- R192G ---

Primary Outcomes

Measure: Geometric Mean Titer (GMT) After First and Second Vaccination With LT Vaccine Patch and Comparison Against Placebo

Time: Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, Day 194

Description: GMFRs relative to the baseline titer were determined at each post-baseline time point. All GMFRs were based on log10-transformed data.

Measure: Geometric Mean Fold Ratio (GMFR) After First and Second Vaccination With LT Vaccine Patch and Comparison Against Placebo

Time: Day 14, Day 21, Day 28, Day 35, Day 90, Day 194

Description: Definition of SCR: Seroconversion IgG: ≥ 2-fold rise of LT IgG titer relative to baseline Seroconversion IgA: ≥ 4-fold rise of LT IgA titer relative to baseline

Measure: Seroconversion (SCR) After First and Second Vaccination With LT Vaccine Patch and Comparison Against Placebo

Time: Day 14, Day 21, Day 28, Day 35, Day 90, Day 194

Secondary Outcomes

Description: LT subjects (Group 1) were followed for six months longer (until Day 380) than Placebo subjects (Group 2) (until Day 194)

Measure: Evaluation of Safety of LT Vaccine Patch After First and Second Vaccination Compared to Placebo Patch

Time: 13 months

Measure: Evaluation of Residual LT in the Patch and on the Skin at the Patch Site Post-wear

Time: 1 month

Description: GMT

Measure: Evaluation of LT-specific Immune Responses One-year After Original Treatment Regimen in LT Patch Group

Time: 13 months

Description: GMFR

Measure: Evaluation of LT-specific Immune Responses One Year After Original Treatment Regimen in LT Patch Group

Time: 13 months

Description: SCR

Measure: Evaluation of LT-specific Immune Responses One Year After Original Treatment Regimen in LT Patch Group

Time: 13 months

6 A Randomized Blinded, LT Dose-ranging Study to Assess the Immunogenicity and Safety of Different Doses of LT Adjuvant Patch Administered in Conjunction With Different Doses of Inactivated Influenza A/H5N1 Vaccine in Healthy Adults

This is a Phase 2, randomized, blinded, clinical trial. Up to 500 eligible subjects will be enrolled and randomized in a 1:2:2:1:2:2 ratio into one of six groups, and vaccinated in this study. Subjects will receive an intramuscular injection of the influenza A/H5N1 (low or high dose) on Day 0 with or without a patch (low or high dose).

NCT00908687
Conditions
  1. Pandemic Influenza
Interventions
  1. Biological: A/H5N1
  2. Biological: A/H5N1
  3. Biological: LT Adjuvant Patch
  4. Biological: LT Adjuvant Patch
MeSH:Influenza, Human

Acceptable forms of birth control are: abstinence, hormonal contraceptives (oral, injectable, implant, patch, ring), double-barrier contraceptives (condom or diaphragm, with spermicide) and IUD Exclusion Criteria: - Clinically significant laboratory abnormalities at screening - Abnormalities at physical examination [as determined by the Toxicity Grading Scale (grade 1-4)] - Known allergies to any component of the vaccine - Known egg protein allergy - Known allergies to adhesives - Known disturbance of coagulation - Participated in research involving investigational product within 45 days before planned date of vaccination - Donated or received blood or blood products such as plasma within the past 45 days - Received any licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to planned date of vaccination - Ever received investigational enterotoxigenic E. coli, or LT (R192G) or NasalFlu, Berna Biotech Ltd - Ever received cholera toxin or vaccine (e.g. --- R192G ---

Primary Outcomes

Description: Seroconversion is defined as either 1) baseline HI titer < 1:10 and a post-vaccination HI titer ≥ 1:40, or 2) baseline HI titer ≥ 1:10 and a minimum four-fold rise. Seroprotection is defined as a post-vaccination HI antibody titer ≥ 1:40.

Measure: Assess the Proportion of Subjects in Each Dose Group Achieving Seroconversion and Seroprotection for HI Antibody Titer Through Day 28.

Time: Day 28

Secondary Outcomes

Measure: Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch

Time: 6 months

Measure: Safety of a 100μg LT Patch

Time: 6 months

Description: The percent of subjects achieving seroconversion for HI antibody titer should meet or exceed 40% The percent of subjects achieving an HI antibody titer ≥ 1:40 should meet or exceed 70% Geometric mean titer (GMT) fold increase > 2.5

Measure: Evaluate Treatment Group HI Responses Against US FDA Guidance for Industry: Clinical Data Needed to Support the Licensure of Pandemic Influenza Vaccines (May 2007) and EMA CPMP/BWP/214/96 Criteria for Immunogenicity

Time: Day 28

Other Outcomes

Measure: Adjuvanticity Evaluation: Compare HI Immune Responses Achieved by Antigen and Adjuvant Combinations With Antigen Alone Groups.

Time: 6 months

Measure: Cross-clade HI Antibody Titer Measurement: Compare the Heterologous HI Antibody Responses to the A/Indonesia/05/2005 (Clade 2.1) Strain of the H5N1 Virus.

Time: 6 months

7 A Phase 2, Gender-Stratified, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of a Two Vaccination Regimen With the Travelers' Diarrhea Vaccine System in Healthy Adults

The purpose of this study is to evaluate and compare the safety and immune responses following a two vaccination regimen by transcutaneous immunization with heat-labile enterotoxin of E. coli (LT) patches or Placebo, with or without alcohol swabbing

NCT01067781
Conditions
  1. Diarrhea
Interventions
  1. Biological: Heat-Labile Enterotoxin of E. coli (LT)
  2. Biological: Placebo
MeSH:Diarrhea
HPO:Diarrhea

Exclusion Criteria: 1. Abnormalities at physical exam [as determined by the Toxicity Grading Scale (Grade 1-4)]; 2. Laboratory abnormalities [as determined by the Toxicity Grading Scale (Grade 1 4)] at screening; 3. Participated in research involving investigational product within 30 days before planned date of first vaccination; 4. Ever received investigational enterotoxigenic E. coli, LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd; 5. Women who are pregnant or breastfeeding; 6. Clinically significant underlying enteric, pulmonary, cardiac or renal disease; 7. Current seizure disorder; 8. Current use of immunosuppressive therapy (inhaled steroids are allowed); 9. Known or suspected alcohol abuse or illicit drug use within the last year; 10. --- R192G ---

Primary Outcomes

Description: Erythema, rash, pain, pruritus, hyperpigmentation, hypopigmentation and edema were solicited local AEs for the duration of the study. Fever, malaise, headache, and diarrhea were solicited systemic AEs for the first seven days following each vaccination; events reported outside this time frame were considered non-solicited.

Measure: Characterization and Comparison of the Safety of the TD Vaccine System: (1) Solicited and Unsolicited Adverse Events (AEs) (2) Clinical Laboratory Safety (3) Serious AEs

Time: Day 0 to Day 180

Secondary Outcomes

Description: LT immunoglobulin G (IgG) and immunoglobulin A (IgA)

Measure: Characterization and Comparison of Group LT-specific Immune Responses to the TD Vaccine System: Geometric Mean Titers

Time: Day 0 to Day 180

Description: LT immunoglobulin G (IgG) and immunoglobulin A (IgA)

Measure: Characterization and Comparison of Group LT-specific Immune Responses to the TD Vaccine System: Geometric Mean Fold Ratios

Time: Day 0 to Day 180

Description: LT immunoglobulin G (IgG) and immunoglobulin A (IgA)

Measure: Characterization and Comparison of Group LT-specific Immune Responses to the TD Vaccine System: Seroconversion Rates

Time: Day 0 to Day 180

8 Phase I Study to Determine the Safety and Immunogenicity of an Oral ETEC Candidate Vaccine, Attenuated, Recombinant Double Mutant Heat-Labile Toxin (dmLT) From Enterotoxigenic Escherichia Coli

The purpose of this study is to learn if a new candidate vaccine (dmLT) against ETEC (E. coli infection) is safe. This vaccine will be tested to see what effects it has on the body and the ability of the vaccine to help the body resist disease. Researchers want to find the highest dose of dmLT vaccine that can be given without causing severe side effects. Most E. coli bacteria are harmless to humans and can even be beneficial. However, some are harmful, and can cause diarrhea. About 32 healthy adults, ages 18-45, will participate in this study. This study will require volunteers to stay in the research facility for several nights. Participants will be assigned to receive 1 of 4 vaccine doses by mouth. Study procedures include: stool samples, blood samples, and documenting side effects. Participants will be involved in study related procedures for about 8 months.

NCT01147445
Conditions
  1. Gastroenteritis Escherichia Coli
Interventions
  1. Biological: Double Mutant Heat- Labile Toxin (dmLT)
MeSH:Gastroenteritis

The rationale for using an E. coli heat labile enterotoxin (LT) (R192G/L211A) vaccine, also called double-mutant LT (dmLT), is that it is expected to be especially well tolerated by subjects. --- R192G ---

Primary Outcomes

Measure: Safety of double-mutant E. coli heat labile enterotoxin (dmLT) vaccine. The occurrence of dose escalation halting events. Additional safety includes the incidence and severity of adverse events (AEs) and changes in laboratory and clinical parameters.

Time: Day 0, follow-up clinic visits (Days 8 ±1, 14 ±2, 28 ±2), and months 2 ±2 weeks, 6 ±2 weeks, by telephone. After Day 28 post vaccination, adverse event follow-up limited to only SAEs, non-routine medical visits, and new-onset chronic medical conditions.

Secondary Outcomes

Measure: Adverse Events.

Time: Through 6 months.

Measure: Immunogenicity: stimulation of anti-dmLT antibody secreting cells (ASC) measured by ELISPOT and seroconversion rates and geometric mean titers of serum anti-LT immunoglobulin (Ig) IgG and IgA antibodies and fecal anti-LT IgA antibodies measured by ELISA.

Time: Serum and stool collected on Days 8, 14, and 28.

9 A Phase 1/2, Randomized, Open-Label, Study to Assess the Immunogenicity and Safety of a Vaccine Enhancement Patch (VEP) When Administered With Two Doses of Intramuscular Inactivated Influenza H5N1 Vaccine in Healthy Adults

Groups 1 to 3 will receive two vaccinations on Day 0 and Day 21. Group 1 will receive 3.8µg A/H5N1 antigen formulated with AS03 adjuvant, administered by IM injection. Group 2 will receive 15µg A/H5N1 by IM alone. Group 3 will also receive 15µg A/H5N1 antigen administered IM but followed by the topical application of a VEP at the vaccination site. Group 4 will receive a single vaccination on Day 0 of 30µg A/H5N1antigen by IM, followed by application of a VEP at the vaccination site. The VEP (Vaccine Enhancement Patch) contains 50 mcg LT (heat-labile enterotoxin of E. coli)

NCT01353534
Conditions
  1. Healthy
Interventions
  1. Biological: A/H5N1 Antigen
  2. Drug: Vaccine Enhancement Patch
MeSH:Influenza in Birds

Exclusion Criteria: - Clinically significant laboratory abnormalities at screening - abnormalities at physical examination - known allergies to any component of the A/H5N1 antigen - known egg protein allergy - known allergies to adhesives - known coagulation disorders - use of any anticoagulant medication within 30 days prior to vaccination or planned usage during the study period - participated in research involving investigational product within 30 days before planned date of vaccination or planned participation during study period - donated or received blood or blood products such as plasma within the three months before planned date of vaccination or planned donation or use during the study period - received or planned receipt of seasonal influenza vaccine during the study period - received any licensed vaccines within 2 weeks (inactivated vaccines) or 4 weeks (live vaccines) prior to planned date of vaccination - planned receipt of any licensed vaccine during the first 42 days on study - previous or planned vaccination with any vaccine containing an oil in water emulsion adjuvant - previous or planned vaccination with pandemic vaccine against A/H5N1 or previous proven contact with A/H5N1 wild type virus - ever received investigational enterotoxigenic E. coli LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd. --- R192G ---

Primary Outcomes

Description: Evaluate hemagglutination inhibition (HI) immune responses to two doses of 15μg A/H5N1 achieved in the antigen plus VEP group versus the antigen alone group (Group 3 vs. Group 2) at Day 42 using standard serological parameters (Geometric Mean Titer [GMT], Geometric Mean Fold Ratio [GMFR], seroconversion and seroprotection).

Measure: Evaluate hemagglutination inhibition (HI) immune responses

Time: Day 42

Secondary Outcomes

Description: Comprehensive assessment of solicited and non-solicited local (vaccination site) and systemic adverse events (AEs) Safety follow-up through six months after last vaccination

Measure: Safety of 15µg and 30µg IM A/H5N1 antigen administered with the 50µg VEP

Time: 8 months

Description: Characterize HI immune responses in the 15µg A/H5N1 antigen alone group (Group 2) and the 15µg A/H5N1 antigen plus VEP group (Group 3) to determine if levels meet or exceed EMA CPMP/BWP/214/96 criteria for immunogenicity: The percent of subjects achieving seroconversion for HI antibody titer should meet or exceed 40% The percent of subjects achieving an HI antibody titer ≥ 1:40 should meet or exceed 70% GMT increase > 2.5

Measure: Characterize HI immune responses

Time: 8 months

10 Safety, Reactogenicity, Tolerability, Immunogenicity and Efficacy of Live Attenuated ETEC ACE527 Vaccine Administered Alone or With a Double Mutant E. Coli Heat Labile Toxin (dmLT) in Healthy Adult Volunteers

This is a research study about an experimental (investigational) oral ETEC vaccine (ACE527). ACE527 is a live attenuated vaccine that is being made to prevent disease from enterotoxigenic Escherichia coli (ETEC), which causes watery diarrhea, largely in children living in developing countries and in travelers to those countries. This research study is also testing an investigational adjuvant called dmLT. An adjuvant is something that is added to a vaccine to make it work better. The purpose of this study is two-fold. First, Part A aims to find out if the vaccine by itself or the vaccine combined with the adjuvant is safe, tolerable, and initiates an immune response. Second, Part B aims to find out if the vaccine by itself or the vaccine combined with the adjuvant prevents diarrheal disease when challenged with ETEC H10407. About 60 healthy adults, ages 18-50, will participate in Part A, and they will be required to stay in the research facility for several nights for the first dose, but will not be required to stay overnight for the second and third doses. Participants will be assigned to receive either the vaccine alone, the vaccine with adjuvant, or placebo by mouth. Study procedures include: stool samples, blood samples, and documentation of side effects. Participants will be involved in study related procedures for about 8 months. Interested volunteers from Part A will along with volunteers who were never vaccinated in Part A will return to participate in Part B. These volunteers will be required to stay overnight in the research facility for several nights after challenge, after which they will be treated with antibiotics and sent home. Study procedures include stool samples, blood samples, and documentation of infection with ETEC H10407. If the vaccine with/without adjuvant is effective, the volunteers should not development diarrhea, but if the vaccine with/without adjuvant is not effective, the volunteers will have diarrhea for a few days.

NCT01739231
Conditions
  1. Diarrhea
Interventions
  1. Biological: ACE527
  2. Biological: dmLT
  3. Biological: CeraVacx placebo
  4. Biological: H10407 challenge strain
MeSH:Diarrhea
HPO:Diarrhea

LT(R192G/L211A), or dmLT, is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. --- R192G ---

Primary Outcomes

Description: Unsolicited adverse events were collected throughout Part A of the study, were graded for severity, and assessed for relationship to vaccine. Withdrawal from the study due to adverse event was determined at the discretion of the study staff.

Measure: Part A: Number of Serious Adverse Events and Adverse Events Leading to Withdrawal

Time: up to 1 month after last vaccination (3 months)

Description: Unsolicited adverse events were collected throughout Part A of the study, were graded for severity, and assessed for relationship to vaccine. Generally, mild severity is discomfort with no disruption of normal daily activities and relieved with or without symptomatic treatment; moderate severity is discomfort sufficient to reduce or affect normal daily activity somewhat and only partially relieved with symptomatic treatment; and severe is discomfort sufficient to reduce or affect normal daily activity considerably; prevents regular activities, and not relieved with symptomatic treatment. Additional description of severity for diarrhea, body temperature, and vomiting is described in the protocol.

Measure: Part A: Number of Participants Experiencing Unsolicited Adverse Events, by Severity and Relationship to Vaccination

Time: up to 1 month after last vaccination (3 months)

Description: Solicited reactions were collected 1 week after each vaccination.

Measure: Part A: Number of Solicited Reactions

Time: up to 1 week after each vaccination (at 0, 1, and 2 months)

Description: Defined as a four-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

Description: Defined as a four-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

Description: Defined as a four-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Pre all vaccinations; day 3 post-vaccination 1 and 2; day 7 post all vaccinations; 4 weeks post-vaccination 3

Description: Defined as a four-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Severe diarrhea was defined as >800 grams of grade 3-5 stools passed over the 120-hour observation period. For episodes starting at or before 120 hours post-challenge, volunteers were followed to resolution and the total stool output weight was considered in determining whether a specific volunteer met the primary definition of severe diarrhea. The end of a diarrheal episode occurred when a volunteer did not pass any grade 3-5 stool in a 24-hour period. Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Number and Percentage of Subjects Experiencing Severe Diarrhea Following H10407 Challenge Strain

Time: 5 days

Secondary Outcomes

Measure: Part A: Number of Participants Shedding E. Coli on Qualification Plate

Time: Pre- and day 7 post-all vaccinations; and Day 3 post-vaccinations 1 and 2; and 4 weeks post vaccination 3

Measure: Part A: Number of Participants With Positive Shedding Results for ACE527

Time: Pre- and day 7 post-all vaccinations; and Day 3 post-vaccinations 1 and 2; and 4 weeks post vaccination 3

Measure: Number of Participants Shedding Vaccine Strains Included in ACE527

Time: 3 days after the first and second vaccinations

Description: Defined as mild, moderate, or severe diarrhea, specifically: Mild diarrhea: 2 or 3grade 3-5 stools totaling 200 g - 400 g, or 1 grade 3-5 stool of >300 g Moderate diarrhea: 4-5 grade 3-5 stools totaling >200 g or 401 - 800g Severe diarrhea: > 800g grade 3-5 stool(s) Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Number and Percentage of Subjects Experiencing Diarrhea of Any Severity

Time: 5 days

Description: Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Mean Total Weight of Grade 3-5 Stools Passed Per Volunteer

Time: 5 days

Description: Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Median Total Weight of Grade 3-5 Stools Passed Per Volunteer

Time: 5 days

Description: Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Mean Number of Grade 3-5 Stools Passed Per Volunteer

Time: 5 days

Description: Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Median Number of Grade 3-5 Stools Passed Per Volunteer

Time: 5 days

Description: Solicited reactions were generally graded as mild if there was discomfort, but no disruption of normal daily activities; moderate if if discomfort was sufficient to affect normal daily activity and partially relieved with symptomatic treatment; severe if discomfort was sufficient to affect normal daily activity considerably, prevent regular activity, and not relieved with symptomatic treatment.

Measure: Part B: Number of Subjects Experiencing Solicited Reactions Graded as Moderate or Severe

Time: 1 week

Description: When asking about adverse events, subjects were asked whether their illness resulting from ETEC would have reduced their daily activity because of their illness if they had been vacationing or traveling on business.

Measure: Part B: Number and Percentage of Subjects Who Would Have Reduced Daily Activity

Time: 5 days

Description: Defined as mild, moderate, or severe diarrhea, specifically: Mild diarrhea: 2 or 3grade 3-5 stools totaling 200 g - 400 g, or 1 grade 3-5 stool of >300 g Moderate diarrhea: 4-5 grade 3-5 stools totaling >200 g or 401 - 800g Severe diarrhea: > 800g grade 3-5 stool(s) Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Mean Time to Onset of Diarrhea Among Subjects Who Had Diarrhea

Time: 5 days

Measure: Part B: Quantity of H10407 Per Gram of Stool on Day 2 Post-challenge

Time: 2 days after vaccination

Measure: Part B: Number of Subjects Requiring Early Antibiotic Treatment and Intravenous (IV) Fluids

Time: 5 days

11 Phase I Evaluation of the Safety, Reactogenicity and Immunogenicity of Fractional-dose Inactivated Polio Vaccine (fIPV) Given Intradermally With Double Mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia Coli Heat Labile Toxin (dmLT) Adjuvant

Polio is a serious disease that can cause paralysis and death. It is caused by a virus and can be prevented by vaccine. The World Health Organization's (WHO) Global Polio Eradication Initiative is trying to get rid of all polio disease around the world. Researchers want to help by testing a new vaccine. In many countries, people are vaccinated with oral polio vaccine (OPV) given by mouth during childhood. OPV is good at giving immunity (protection from polio) in the body and the gastrointestinal (GI) tract. Immunity in the GI tract is called mucosal immunity. The downsides of using OPV are that it can be shed into the environment in people's feces after vaccination where it can infect people who are not vaccinated, and it can cause paralysis in 2-4 of every one million children vaccinated with OPV. The United States (U.S.) stopped giving any OPV to people for vaccinations in the 1990's. Since then, a polio vaccine called inactivated polio vaccine (IPV) is given as an injection for routine childhood immunizations in the U.S. You cannot get polio infection from IPV and it will not be shed into the environment. In 2016, the WHO started a plan to help other countries gradually get rid of OPV. The downside of using IPV by itself is that, unlike OPV, it doesn't give enough mucosal immunity to protect people living in places where there is still polio. There are also supply shortages of IPV, which is a problem if there are outbreaks of polio. For the supply of IPV to help more people, it is safe and effective to use a tiny dose of IPV injected under the top layer of skin (intradermal or ID injection) rather than getting the full dose in the muscle. This is called a fractional dose of IPV, or fIPV. To help stop using OPV globally, a better fIPV vaccine is needed. fIPV vaccine needs a substance to help stimulate a mucosal immune response. dmLT is a substance that has been shown to stimulate a mucosal immune response. It has been shown to be safe and effective in both humans and animals, both by itself and when given with other vaccines. This study will test a mixture of fIPV-dmLT given intradermally (under the outer layer of the skin). This is the first study done in humans to give this combination intradermally. The IPV vaccine has already been approved by the FDA. The fIPV-dmLT vaccine has not been approved by the FDA.

NCT03922061
Conditions
  1. Polio
Interventions
  1. Biological: dmLT
  2. Biological: fIPV
MeSH:Poliomyelitis

Phase I Evaluation of the Safety, Reactogenicity and Immunogenicity of Fractional-dose Inactivated Polio Vaccine (fIPV) Given Intradermally With Double Mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia Coli Heat Labile Toxin (dmLT) Adjuvant. --- R192G ---

Primary Outcomes

Description: frequency of systemic and local injection site adverse reactions (ARs) defined as vaccine-related adverse events (AEs), graded by severity

Measure: frequency of systemic and local injection (safety and reactogenicity)

Time: Events occuring within 28 days of dosing

Secondary Outcomes

Description: percentage of subjects with at least one serious adverse event (SAE) occurring within 28 days of dosing will be summarized with severity, relationship to vaccine, and outcome

Measure: percentage of subjects with at least one serious adverse event (secondary-safety)

Time: Events occuring within 28 days of dosing

Description: Proportion of participants showing at least a 4-fold boost in polio-specific serum neutralizing antibodies compared to baseline (Day 0) in fIPV-dmLT recipients vs. fIPV alone

Measure: Systemic immunogenicity

Time: Any timepoint up to day 28 post-vaccination


HPO Nodes


HP:0002014: Diarrhea
Genes 392
AVP TRNL1 MCM6 COG4 ANTXR2 LIPA CD247 HBB WNT2B TYMP MYO5B HMGCS2 DGAT1 IL2RG ALG3 TTR DAXX SERPING1 SLC5A1 BMPR1A EGFR ABCC8 SI PTEN SMARCD2 DBH KRAS BLNK TSHR PRKN LRRK2 PPP2R5D DNAJC6 KIF1B CD247 IKBKB SCNN1B AGA ADA RAG1 RAG1 COX2 TXNRD2 CARMIL2 BTD IL21R ABCB11 ERCC2 ATP8B1 G6PC CYP7B1 NAGLU STX3 IGHM ERCC4 CD79A TLK2 KCNJ1 TRNH FBP1 MPI MRAP SLC46A1 HGSNAT RET TTR TTC37 GINS1 TET2 BTK IL7R TCN2 RNF113A PIK3CD NBN RET ACTG2 IL2RB RAG2 CD19 ACADM HLA-B RFX6 HNF4A ITCH CD40LG ICOS POLG IDUA CFHR3 MPV17 SAA1 FOXP3 MEFV AP1S1 CIITA IGKC ENG TRNS2 TRNS1 RAG2 ZAP70 STAR NOD2 RECQL4 BRCA2 RFXANK IL6 ITGB3 HBB ITGA2 HYOU1 GATA6 ND4 EGFR BRCA1 ELANE SLC19A2 ND5 SPINT2 IL7R SCNN1A TCIRG1 COX1 SMAD4 CYP27A1 SAMD9 RAG1 LIPA SERPING1 IL21 SDHD CD55 BMPR1A TTC37 GUCY2C ATP7A LCT RFX5 SKIV2L DCLRE1C SON HMBS IRAK1 JAK3 CD109 POLA1 RRM2B RAG2 ITGB4 CTLA4 TERT HMGCL ECE1 CIITA SLC25A13 BTK SLC9A3 TRNF NEUROG3 CFHR1 ZAP70 GP1BA FOXP3 KIF23 KNSTRN TYMP NR3C2 TCF3 HEXB UCHL1 ICOS NNT POLG CDKN1A NEUROG3 TNFRSF13B ADA EPCAM CYP11B2 CCDC47 SLC10A2 UCP2 NSUN2 SRP54 PARK7 IGHM IL10RA NRTN GREM1 DCLRE1C RIPK1 LIG4 OPLAH MC2R AK2 CD79A IL2RG CYP27A1 PLEC ACAT1 CDKN1B MEN1 SCNN1G SLC39A4 TNFRSF13C PINK1 STAT1 HMBS SMAD4 DNMT3B CHD7 MVK PERCC1 COG4 STAT4 EDNRB ALDOB LRBA KCNJ11 RFXAP ATRX SYNJ1 TREH CFH CR2 TRNQ HPS1 CD3D SEMA3C DNASE1L3 SMAD4 SGSH WAS CDKN2C PODXL USP7 CDKN2A SPP1 MLYCD IL6ST LRRC8A ACSF3 TKFC NAGS ETHE1 SAR1B ASXL1 GDNF IGLL1 CD79B B2M NCF4 SLC25A13 ALAD CD79B BLNK SLC7A7 EDN3 LCK HNF1A RAG2 CD3E COX3 MGME1 TTC7A NLRC4 CLMP MEN1 ABCB4 RNF168 VPS13C SNCA ND1 NAXD NOD2 MYD88 TP53 BMPR1A PIK3R1 CR2 MTTP SERPING1 APC CASP8 SLC12A3 PKP1 CPT1A ADA AIRE PLVAP IKZF1 DES F5 RFXANK IL2RA CLCNKB IL2RG WDR1 HSD3B7 MGME1 TTC7A ADAM17 OTULIN BTK BACH2 PALLD SRSF2 RUNX1 WIPF1 CD3D MAOA ITGA6 RFX5 C5 DCLRE1C ASAH1 SUGCT PALB2 GLA MEFV ACVRL1 MVK SCN11A BMPR1A COG6 CBL SLC39A4 ITGA2B HADH TSHR ANTXR2 SLC12A1 SP110 TMPRSS15 PPP2R5D PMM2 PIGT ERCC8 TFRC ETHE1 TRNW ARX IFNG TNFRSF1A SCN9A ND6 MYO5B RFXAP ACSF3 RAG1 ALG8 SMAD4 CPOX ENG PCSK1 RMRP WAS MVK PTPRC ELP1 GFI1 AKR1D1 SLC46A1 DDC ADAM17 ERCC6 SLC7A7 SAR1B CDKN2B PIK3R1 PHKB RECQL4 SKIV2L JAK3 DMPK LIG4 IL7R NHLRC2 TGFB1 CDKN1B GALT IFNGR1 SLC26A3 IDS GP1BB EFL1 SEMA3D HTRA2 NBN GNS STAT1
Protein Mutations 1
R192G
SNP 0