CovidResearchTrials by Shray Alag


CovidResearchTrials Covid 19 Research using Clinical Trials (Home Page)


Report for D006467: Hemophilia A NIH

(Synonyms: Hema, Hemophilia, Hemophilia A)

Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation


Correlated Drug Terms (5)


Name (Synonyms) Correlation
drug1731 PEGylated Recombinant Factor VIII Wiki 0.50
drug277 BAX 888 Wiki 0.50
drug68 ADVATE Wiki 0.50
drug911 FEIBA Wiki 0.50
drug69 ADYNOVI Wiki 0.50

Correlated MeSH Terms (0)


Name (Synonyms) Correlation

Correlated HPO Terms (1)


Name (Synonyms) Correlation
HP:0003125 Reduced factor VIII activity HPO 1.00

There are 4 clinical trials

Clinical Trials


1 ADVATE/ ADYNOVI Hemophilia A Outcome Database

The purpose of the study is to document the natural history of hemophilia A disease and long-term outcomes in terms of effectiveness, safety and quality of life in participants receiving Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) or Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG) in routine clinical practice

NCT02078427 Hemophilia A Biological: ADVATE Biological: ADYNOVI
MeSH:Hemophilia A
HPO:Reduced factor VIII activity

Primary Outcomes

Description: The World Federation of Hemophilia developed a musculoskeletal evaluation system, commonly referred to as the Gilbert test, to measure hemophilia joint health status.The Gilbert test needs to be performed in the absence of acute bleed, acute pain, and acute inflammation into the evaluated joint. Four parameters are used in each Gilbert test: pain (score: 0-3), bleeding (score: 0-3), physical exam (score: 0-12), and X-ray evaluation (score: 0-13) Scores of 0, represent no pain, no bleeding, no physical exam issues, and/or no x-ray issues. Higher scores for each of these categories represents worsening conditions.

Measure: Joint Health Outcomes - Assessed by Physical Exam Using Only the Pain, Bleeding, and Physical Exam Parameters of the Gilbert Scale

Time: Up to approximately 12 years

Secondary Outcomes

Description: The annualized bleed rate for all joints will be calculated per participant and summarized over the set of available participants with a minimum observation period of 90 days per treatment regimen.

Measure: Annualized Bleed Rate, All Joints

Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: The annualized bleed rate for all bleeds will be calculated per participant and summarized over the set of available participants.with a minimum observation period of 90 days per treatment regimen.

Measure: Annualized Bleed Rate, All Bleeds

Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: The annualized bleed rate for pre-existing target joints at baseline will be calculated per participant and summarized over the set of available participants with a minimum observation period of 90 days per treatment regimen.

Measure: Annualized bleed rate, pre-existing target joints at baseline

Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: The incidence of new target joints will be calculated as the total number of new target joints in all participants divided by the total number of observation days.

Measure: Incidence of New Target Joints

Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: The status of joint health by X-ray by Pettersson score will be summarized for each observational year.

Measure: Status of joint health by X-ray by Pettersson scale

Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit.

Description: LSS score format= A(e:s:h). Sum of values for Subchondral Cyst (score: 1-6), irregularity/erosion of Subchondral Cortex (score: 1-4), and Chondral Destruction (score: 1-6) gives value for the A component of score. e, s, h components represent effusion/hemarthrosis, hypertrophic synovial, & hemosiderin deposition (score: 0-4 for each). Max. score is 16(4:4:4). Subchondral Cyst: ≥1 bone ≥2 bones >3 cysts in ≥1 bone >3 cysts ≥2 bones Largest size >4 mm: ≥1 bone Largest size >4 mm: ≥2 bones Subchondral Cortex ≥1 bone ≥2 bones Involve > half joint surface: ≥1 bone Involve > half of joint surface: ≥2 bones Chondral Destruction ≥1 bone ≥2 bones Full thickness defect (FTD): ≥1 bone FTD: ≥2 bones FTD involves >1/3 of joint surface: ≥1 bone FTD involves >1/3 of joint surface: ≥2 bones Effusion/hemarthrosis (e): Hypertrophic synovial (s): Hemosiderin (h): (0-4 for each): 0 absent 1 equivocal 2 small 3 moderate 4 large

Measure: Status of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS)

Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: The International Prophylaxis Study Group (IPSG) developed a scoring system for musculoskeletal evaluation, the HJHS, optimized for use in children with no or minimal joint disease. The HJHS includes the following parameters: swelling, duration of swelling, muscle atrophy, joint pain, crepitus on motion, flexion loss, extension loss, strength and global gait.

Measure: Status of joint health using the Hemophilia Joint Health Score (HJHS)

Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: Excellent: Same or lower breakthrough bleed rate (BBR) within last 12 months (M) compared with prior prophylaxis; if participant did not receive prior prophylaxis with rAHF-PFM, rAHF-PEG or other Factor VIII (FVIII), same or better than expected outcome according to investigator's expectation Good: Minor increase in BBR within last 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, slightly less than expected outcome according to investigator's expectation Fair: Moderate increase in BBR in last 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, somewhat less than expected outcome according to investigator's expectation Poor: Significant increase in BBR in the 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, little to no benefit according to investigator's expectation

Measure: Overall effectiveness assessment for prophylaxis therapy

Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone;- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years;- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: Evaluation of patients´ compliance to prescribed prophylactic treatment will be performed by the treating physician. Compliance will be categorized according to a 4-point table (Highly compliant, Fairly compliant, Moderately compliant, Poorly compliant)

Measure: Compliance with the dosing prescribed and its relationship with effectiveness

Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone;- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years;- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: Excellent: Bleed episodes typically respond to same or fewer number of infusion and same or lower dose as compared with previous on-demand treatment or investigator's expectation Good: Most bleed episodes typically respond to same number of infusion and dose but some require more infusions or higher dose as compared with previous on-demand treatment or investigator's expectation Fair: Bleed episodes typically require more infusions and/or higher dose than expected as compared with previous on-demand treatment or investigator's expectation Poor: Bleed episodes routinely fail to respond to same number of infusion and dose and require additional or different factor concentrate for hemostatic control as compared with previous on-demand treatment or investigator's expectation

Measure: Overall effectiveness assessment for on-demand treatment

Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: Excellent: Full relief of pain and cessation of bleeding as evidenced by objective signs (e.g., swelling, tenderness, irritability, inconsolability, and decreased range of motion in the case of musculoskeletal hemorrhage) within approximately 8 hours of a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusions to maintain hemostasis would not affect this scoring. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after the infusion. Possibly requires more than 1 infusion for complete resolution. Fair: Probable or slight relief of pain and slight improvement in signs of bleeding within approximately 8 hours after the infusion. Requires more than 1 infusion for complete resolution. Poor: No improvement or condition worsens.

Measure: Global effectiveness assessment for on-demand treatment

Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)

Measure: Number of rAHF-PFM or rAHF-PEG units required for bleed cessation

Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Description: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)

Measure: Number of rAHF-PFM or rAHF-PEG infusions required for bleed cessation

Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Measure: Incidence of target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy

Time: Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit

Measure: Incidence of pseudo tumor development

Time: Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: The the lHAL measures activities involving the upper extremities, basic activities involving ower extremities and complex activities involving the lower extremities as well as an overall physical activity score for adults.

Measure: Quality of Life: HAL questionnaire - for adult patients

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: The SF-12v2 measures generic health-related quality of life for adults.

Measure: Quality of Life: SF-12v2 questionnaire - for adult patients

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: The EQ-5D measures health utility in adult participants.

Measure: Quality of Life: EQ-5D questionnaire - for adult patients

Time: Enrollment visit;Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: The PedHAL measures activities involving the upper extremities, basic activities involving the lower extremities and complex activities involving the lower extremities as well as an overall physical activity score for children. For participants 4-13 years of age: - PedHAL (parent version) For participants 14-17 years of age: - PedHAL (child version)

Measure: Quality of Life: PedHAL questionnaire - for pediatric patients

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: The SF-10 measures generic health-related quality of life for children and is parent-completed.

Measure: Quality of Life: SF-10 questionnaire - for pediatric patients

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: The EQ-5D measures health utility in subjects aged 14 and up.

Measure: Quality of Life: EQ-5D (14 and up) questionnaire - for pediatric patients

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain). During screening visit and on an annual basis, the investigators shall ask participants to rate the average level of chronic pain associated with hemophilia over the period of 4 weeks prior to visit date using the VAS.

Measure: Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS)

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain). Participants will be asked to provide ratings on level of acute pain associated with each bleeding episode using the VAS. The VAS scores will be recorded in the participant diary.

Measure: Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS)

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Measure: Number of days lost from school or work due to bleeding episodes

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: Difference in number of weekly prophylactic infusions between previous regimen and rAHF-PEG

Measure: Modalities of switching from a standard FVIII product to rAHF-PEG - 1

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Description: Difference in number of weekly doses between previous regimen and rAHFPEG

Measure: Modalities of switching from a standard FVIII product to rAHF-PEG - 2

Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit

Measure: Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels Lesser than (<)1%, Lesser Than or Equal to (<=) 2%, and <= 5% without history of inhibitor

Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)

Measure: Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% with history of inhibitor

Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)

Measure: Incidence of Inhibitors in Previously Untreated Patient (PUPs) and Minimally Treated Patients (MTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5%

Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)

Measure: Incidence of therapy-related serious adverse events

Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)

Measure: Incidence of therapy-related non-serious adverse events

Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)

Description: Incidence of inhibitors after switching to rAHF-PEG in the same subgroups of patients

Measure: Incidence of inhibitors after switching to rAHF-PEG

Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)

2 Phase 3, Prospective, Multi-center, Open Label Study to Investigate Safety, Immunogenicity and Hemostatic Efficacy of PEGylated Factor VIII (BAX 855) in Previously Untreated Patients (PUPs) < 6 Years With Severe Hemophilia A (FVIII < 1%)

The purpose of this study is to investigate safety, immunogenicity and hemostatic efficacy of PEGylated recombinant FVIII (BAX 855) in previously untreated patients (PUPs) < 6 years of age with severe hemophilia A (baseline FVIII level < 1%) and < 3 EDs to ADVATE, BAX 855 or plasma transfusion.

NCT02615691 Hemophilia A Biological: PEGylated Recombinant Factor VIII
MeSH:Hemophilia A
HPO:Reduced factor VIII activity

Primary Outcomes

Measure: Incidence of FVIII inhibitor development

Time: Throughout Part A of the study, approximately 5 years

Measure: Success rate of Immune tolerance induction (ITI)

Time: Up to 33 months

Secondary Outcomes

Description: Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG)

Measure: Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies

Time: Throughout Part A of the study, approximately 5 years

Measure: Clinically significant adverse events (AEs) and serious adverse events (SAEs)

Time: Throughout Part A and Part B of the study, approximately 7 years

Measure: Clinically significant changes in vital signs

Time: Throughout Part A and Part B of the study, approximately 7 years

Measure: Clinically significant changes in clinical laboratory parameters

Time: Throughout Part A and Part B of the study, approximately 7 years

Measure: Annualized bleeding rate (ABR) for prophylactic and on-demand treatment

Time: Throughout Part A of the study, approximately 5 years

Measure: Number of BAX 855 infusions per bleeding episode

Time: Throughout Part A of the study, approximately 5 years

Measure: Overall hemostatic efficacy rating

Time: 24 h after initiation of treatment and at resolution of bleed

Measure: Weight-adjusted consumption of BAX 855 per month, per year and per event

Time: Throughout Part A of the study, approximately 5 years

Measure: Number of infusions per month and per year

Time: Throughout Part A of the study, approximately 5 years

Measure: Assessment of intra-, post- and perioperative hemostatic efficacy in case of surgery

Time: Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first)

Measure: Intra- and postoperative blood loss in case of surgery

Time: Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first)

Measure: Pharmacokinetics- Incremental recovery (IR) at baseline and over time

Time: Pre-infusion within 30 minutes; and post-infusion at 15-30 minutes and 24-48 hours

Measure: Pharmacokinetics- Half-life (T1/2) at baseline (optional)

Time: Post-infusion: 15-30 minutes and 24-48 hours

Measure: Immune tolerance induction (ITI) - Rate of partial success and failure of ITI

Time: Up to 33 months

Measure: Immune tolerance induction (ITI) - annualized bleeding rate (ABR) during ITI

Time: Up to 33 months

Measure: Immune tolerance induction (ITI) - Weight-adjusted consumption of BAX 855 per month and per year for each ITI regimen employed

Time: Up to 33 months

Measure: Immune tolerance induction (ITI) - Catheter-related complications

Time: Up to 33 months

Description: Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG)

Measure: Immune tolerance induction (ITI) -Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies

Time: Up to 33 months

3 A Phase 3b/4, Prospective, Multicenter, Open-label, Randomized, Crossover Study of Tolerability and Safety of FEIBA Reconstituted in Regular or 50% Reduced Volume and of Faster Infusion Rates in Patients With Hemophilia A or B With Inhibitors

The purpose of this study is to: - 1. To evaluate the tolerability and safety of infusing reduced volume Factor Eight Inhibitor Bypassing Activity (FEIBA) at the standard infusion rate of 2 U/kg/min - 2. To evaluate the tolerability and safety of infusing reduced volume FEIBA at increased rates of 4 and 10 U/kg/min, in comparison to the standard rate of 2 U/kg/min at the regular volume

NCT02764489 Hemophilia A or B With Inhibitors Biological: FEIBA
MeSH:Hemophilia A
HPO:Reduced factor VIII activity

Primary Outcomes

Description: Number of participants with serious adverse events (SAEs) and non-SAEs will be assessed.

Measure: Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events

Time: Throughout the study period of approximately 13 months

Description: Number of participants with AEs particular to allergic-type hypersensitivity reactions will be assessed.

Measure: Number of Participants With Adverse Events (AEs) Related to Hypersensitivity Reactions

Time: Throughout the study period of approximately 13 months

Description: Number of participants with AEs particular to thromboembolic events will be assessed.

Measure: Number of Participants With Adverse Events (AEs) Related to Thromboembolic Events

Time: Throughout the study period of approximately 13 months

Description: Number of participants with AEs related to infusion site reactions will be assessed.

Measure: Number of Participants With Adverse Events (AEs) Related to Infusion Site Reactions

Time: Throughout the study period of approximately 13 months

Description: Number of participants with adverse events (AEs) leading to discontinuation will be assessed.

Measure: Number of Participants With Adverse Events (AEs) Leading to Discontinuation

Time: Throughout the study period of approximately 13 months

Description: Number of participants with AEs related to change in vital signs will be assessed. Vital signs will include body temperature (degree Celsius or degrees Fahrenheit [°C or °F]), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (millimeter of mercury [mmHg]).

Measure: Number of Participants With Adverse Events (AEs) Related to Change in Vital Signs

Time: Throughout the study period of approximately 13 months

Description: Number of participants with AEs related to change in laboratory assessments will be assessed. Laboratory assessments include hematology, clinical chemistry, coagulation testing, serological testing, pregnancy testing, cluster differentiation 4 (CD4).

Measure: Number of Participants With Adverse Events (AEs) Related to Change in Laboratory Assessments

Time: Throughout the study period of approximately 13 months

4 A Global, Open-Label, Multicenter, Phase 1/2 Study of the Safety and Dose Escalation of BAX 888, an Adeno-Associated Virus Serotype 8 (AAV8) Vector Expressing B-Domain Deleted Factor VIII (BDD-FVIII) in Severe Hemophilia A Subjects Administered a Single Intravenous Infusion

The purpose of this study is to evaluate the safety and determine the dose of BAX 888.

NCT03370172 Hemophilia A Drug: BAX 888
MeSH:Hemophilia A
HPO:Reduced factor VIII activity

Primary Outcomes

Description: An AE is defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. A Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. AEs include both serious and non-serious adverse events including development of FVIII inhibitory antibodies, clinically significant changes in standard laboratory parameters, physical exam, and vital signs.

Measure: Number of Participants With BAX 888-Related Adverse Events (AEs)

Time: From study drug administration to 3 Years

Secondary Outcomes

Description: Change from baseline in circulating plasma FVIII activity level, based on one-stage clotting assay will be assessed.

Measure: Change from Baseline in Circulating Plasma FVIII Activity Level

Time: Baseline, up to approximately 3 years per participant

Description: Change from baseline in circulating plasma FVIII antigen (protein) levels will be assessed.

Measure: Change from Baseline in Circulating Plasma FVIII Antigen Level

Time: Baseline, up to approximately 3 years per participant

Description: Annualized bleed rate (ABR) in comparison to before gene transfer will be assessed. A bleed is defined as subjective or objective evidence of bleeding which may or may not require treatment with FVIII. Annualized bleed rate (ABR) was calculated as (number of bleeding episodes/observed treatment period in days)*365.25.

Measure: Annualized bleed rate (ABR)

Time: Throughout the study period of approximately 3 years per participant

Description: The percentage of participants with a reduction in exogenous FVIII consumption 12 months post-infusion and 3 years post-infusion compared to the historical consumption (consumption of exogenous FVIII during the 12 month period prior to BAX 888 infusion).

Measure: Percentage of Participants with a Redaction Consumption of Exogenous Factor VIII (FVIII)

Time: Historical data from 12 months prior to study enrollment; and 12 months post-infusion and 3 years post-infusion

Description: Number of participants develop inhibitory antibodies to FVIII will be assessed.

Measure: Number of Participants Develop Inhibitory Antibodies to FVIII

Time: Throughout the study period of approximately 3 years per participant

Description: Number of participants develop total binding antibodies to FVIII (Immunoglobulin G [IgG] and Immunoglobulin M [IgM]) will be assessed.

Measure: Number of Participants Develop Total Binding Antibodies to FVIII

Time: Throughout the study period of approximately 3 years per participant

Description: Number of participants with humoral (antibody-mediated) and cell-mediated immune response to adeno-associated virus (AAV8) (the vector) and FVIII proteins will be assessed.

Measure: Number of Participants With Humoral and Cell-Mediated Immune Response to AAV8 and Factor VIII (FVIII) Proteins

Time: Throughout the study period of approximately 3 years per participant

Description: Surveillance of adeno-associated virus (AAV8) genome shedding in blood, saliva, semen, urine and stool will be assessed.

Measure: Surveillance of AAV8 Genome Shedding

Time: Throughout the study period of approximately 3 years per participant,or until 2 consecutive measurements are negative, which ever is sooner


HPO Nodes