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Report for D054179: Angioedemas, Hereditary NIH

(Synonyms: Angioedemas, H, Angioedemas, Hereditary)

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


Correlated Drug Terms (7)


Name (Synonyms) Correlation
drug1552 Lanadelumab Wiki 0.82
drug2564 Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA] Wiki 0.71
drug391 Berberine Wiki 0.71
drug2563 Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA] Wiki 0.71
drug399 Best available treatment Wiki 0.71
drug1782 Montmorrillonite Wiki 0.71
drug2122 Placebo Wiki 0.04

Correlated MeSH Terms (1)


Name (Synonyms) Correlation
D000799 Angioedema NIH 1.00

Correlated HPO Terms (1)


Name (Synonyms) Correlation
HP:0100665 Angioedema HPO 1.00

There are 2 clinical trials

Clinical Trials


1 SPRING STUDY: An Open-Label, Multicenter, Phase 3 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab for Prevention Against Acute Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects 2 to <12 Years of Age

The purpose of this phase 3, open-label, multicenter study is to evaluate the safety, PK, and PD of lanadelumab in children with age of 2 years to <12 years with Hereditary Angioedema (HAE).

NCT04070326 Hereditary Angioedema (HAE) Drug: Lanadelumab
MeSH:Angioedema Angioedemas, Hereditary
HPO:Angioedema

Primary Outcomes

Description: An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. A SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, is an important medical event. Adverse events of special interest for this study are hypersensitivity reactions and disordered coagulation (hypercoagulability events and bleeding events).

Measure: Number of Participants with Adverse Events Including Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI)

Time: From start of study treatment up to Follow up (Day 392)

Description: Plasma concentrations (cmax) of lanadelumab over the treatment period will be assessed.

Measure: Plasma Concentrations of Lanadelumab Over the Treatment Period

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Maximum observed concentration at steady state (Cmax,ss) of lanadelumab in plasma will be assessed.

Measure: Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Average concentration over Dosing interval at steady state (Cavg,ss) of lanadelumab in plasma will be assessed.

Measure: Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Predose concentration at steady state (Ctrough,ss) of lanadelumab in plasma will be assessed.

Measure: Predose Concentration at Steady State (Ctrough,ss) of Lanadelumab in Plasma

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Time to reach Cmax (tmax) of lanadelumab in plasma will be assessed.

Measure: Time to Reach Maximum Observed Concentration (Cmax) (tmax)of Lanadelumab in Plasma

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Area under the concentration-time curve over the dosing interval at steady state (AUCtau,ss) of lanadelumab in plasma will be assessed.

Measure: Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Lanadelumab in Plasma

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Terminal half-life (t1/2) of lanadelumab in plasma will be assessed.

Measure: Terminal half-life (t1/2) of Lanadelumab in Plasma

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Apparent clearance (CL/F) of lanadelumab will be assessed.

Measure: Apparent clearance (CL/F) of Lanadelumab

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Apparent volume of distribution (V/F) of lanadelumab will be assessed.

Measure: Apparent Volume of Distribution (V/F) of Lanadelumab

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Secondary Outcomes

Description: The normalized number of investigator-confirmed HAE attacks during each efficacy evaluation period will be expressed as a monthly HAE attack rate. A HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Overall treatment period of the study is from Day 0 (after start of study drug administration) through Day 364 (Week 52).

Measure: Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period

Time: From start of study treatment up to Follow up (Day 392)

Description: Efficacy evaluation period consists of overall treatment period (Day 0 [after study drug administration] through Day 364 [Week 52]), treatment Period A (Day 0 [after study drug administration] through Day 182 [Week 26]), treatment Period B (Day 183 through Day 364 [Week 52]), overall presumed steady state period (Day 70 [Week 10] through Day 364 [Week 52]), presumed steady state period for treatment period A (Day 70 [Week 10] through Day 182 [Week 26]).

Measure: Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period

Time: Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Description: Time to the first investigator-confirmed HAE attack (days) for each efficacy evaluation period will be calculated from the date and time of the first dose of lanadelumab for that efficacy evaluation period to the date and time of the first investigator-confirmed HAE attack after the first open-label dose for that efficacy evaluation period. Efficacy evaluation period consists of overall treatment period (Day 0 [after study drug administration] through Day 364 [Week 52]), treatment Period A (Day 0 [after study drug administration] through Day 182 [Week 26]), treatment Period B (Day 183 through Day 364 [Week 52]), overall presumed steady state period (Day 70 [Week 10] through Day 364 [Week 52]), presumed steady state period for treatment period A (Day 70 [Week 10] through Day 182 [Week 26]).

Measure: Time to the First Investigator-Confirmed Hereditary Angioedema (HAE) Attack for Each Evaluation Period

Time: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Description: Efficacy evaluation period consists of overall treatment period (Day 0 [after study drug administration] through Day 364 [Week 52]), treatment Period A (Day 0 [after study drug administration] through Day 182 [Week 26]), treatment Period B (Day 183 through Day 364 [Week 52]), overall presumed steady state period (Day 70 [Week 10] through Day 364 [Week 52]), presumed steady state period for treatment period A (Day 70 [Week 10] through Day 182 [Week 26]).

Measure: Normalized Number of Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period

Time: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Description: Efficacy evaluation period consists of overall treatment period (Day 0 [after study drug administration] through Day 364 [Week 52]), treatment Period A (Day 0 [after study drug administration] through Day 182 [Week 26]), treatment Period B (Day 183 through Day 364 [Week 52]), overall presumed steady state period (Day 70 [Week 10] through Day 364 [Week 52]), presumed steady state period for treatment period A (Day 70 [Week 10] through Day 182 [Week 26]). Severe attack is defined as grade 3 (some assistance usually required, medical intervention/therapy required, hospitalizations possible), moderate attack is defined as grade 2 (some assistance may be needed, no or minimal medical intervention/therapy required).

Measure: Normalized Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks for Each Efficacy Evaluation Period

Time: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Description: Efficacy evaluation period consists of overall treatment period (Day 0 [after study drug administration] through Day 364 [Week 52]), treatment Period A (Day 0 [after study drug administration] through Day 182 [Week 26]), treatment Period B (Day 183 through Day 364 [Week 52]), overall presumed steady state period (Day 70 [Week 10] through Day 364 [Week 52]), presumed steady state period for treatment period A (Day 70 [Week 10] through Day 182 [Week 26]). A high morbidity HAE attack is defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation <24 hours), hemodynamically significant (systolic blood pressure <90, requires intravenous (IV) hydration or associated with syncope or near-syncope) or laryngeal.

Measure: Normalized Number of High Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks for Each Efficacy Evaluation Period

Time: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Description: Characteristics of investigator-confirmed HAE attacks for each efficacy evaluation period includes duration, severity, attack location, and rescue medication use. Efficacy evaluation period consists of overall treatment period (Day 0 [after study drug administration] through Day 364 [Week 52]), treatment Period A (Day 0 [after study drug administration] through Day 182 [Week 26]), treatment Period B (Day 183 through Day 364 [Week 52]), overall presumed steady state period (Day 70 [Week 10] through Day 364 [Week 52]), presumed steady state period for treatment period A (Day 70 [Week 10] through Day 182 [Week 26]).

Measure: Number of Participants with Characteristics of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks for Each Efficacy Evaluation Period

Time: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Description: The number of particpiants who are attack-free will be summarized for each efficacy evaluation period. Efficacy evaluation period consists of overall treatment period (Day 0 [after study drug administration] through Day 364 [Week 52]), treatment Period A (Day 0 [after study drug administration] through Day 182 [Week 26]), treatment Period B (Day 183 through Day 364 [Week 52]), overall presumed steady state period (Day 70 [Week 10] through Day 364 [Week 52]), presumed steady state period for treatment period A (Day 70 [Week 10] through Day 182 [Week 26]).

Measure: Number of Participants with Hereditary Angioedema (HAE) Attack-Free Status for Each Evaluation Period

Time: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Description: pKal activity will be measured by biomarker cleaved high molecular weight kininogen (cHMWK )level to assess pharmacodynamics of lanadelumab.

Measure: Plasma Kallikrein (pKal) Activity

Time: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Description: Immunogenicity will be measured based on the presence or absence of neutralizing or non-neutralizing Anti-drug Antibody (ADA) in plasma.

Measure: Number of Participants with Positive Immunogenicity

Time: Day 0 (Pre-dose), Day 28, 84, 140, 182, 196, 252, 308, 364 and 392

2 A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH) and Acquired Angioedema (AAE) Due to C1-INH Deficiency

The purpose of this study is to evaluate the safety and efficacy of repeated subcutaneous (SC) administrations of lanadelumab in preventing angioedema attacks in adolescents and adults with non-histaminergic angioedema with normal C1-INH and in adults with acquired angioedema (AAE) due to C1-INH deficiency.

NCT04206605 Angioedema Drug: Lanadelumab Other: Placebo
MeSH:Angioedema Angioedemas, Hereditary
HPO:Angioedema

Primary Outcomes

Description: An angioedema attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 will be assessed.

Measure: Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

Time: Day 0 through Day 182

Secondary Outcomes

Description: Number of participants achieving attack-free status during the treatment period of day 0 through day 182 will be assessed.

Measure: Number of Participants Achieving Attack-Free Status During the Treatment Period of Day 0 Through Day 182

Time: Day 0 through Day 182

Description: Moderate attack is defined as grade 2 (some assistance may be needed, no or minimal medical intervention/therapy required), Severe attack is defined as grade 3 (some assistance usually required, medical intervention/therapy required, hospitalizations possible). Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period of day 0 through day 182 will be assessed.

Measure: Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

Time: Day 0 Through Day 182

Description: Number of investigator-confirmed angioedema attacks during the presumed steady state period of day 70 through day 182 will be assessed.

Measure: Number of Investigator-Confirmed Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Number of participants achieving attack-free status during the presumed steady state period of day 70 through day 182 will be assessed.

Measure: Number of Participants Achieving Attack-Free Status During the Presumed Steady State Period of Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Number of investigator-confirmed moderate or severe angioedema attacks during the presumed steady state period of day 70 through day 182 will be assessed.

Measure: Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Number of participants with maximum attack severity during the presumed steady state period of day 70 through day 182 will be assessed.

Measure: Number of Participants with Maximum Attack Severity During Presumed Steady State Period of Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Number of participants with maximum attack severity during treatment period of day 0 through day 182 will be assessed.

Measure: Number of Participants with Maximum Attack Severity During Treatment Period of Day 0 Through Day 182

Time: Day 0 through Day 182

Description: The time to the first angioedema attack (days) after Day 0 for the efficacy evaluation period of Day 0 through Day 182 will be calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 0 through Day 182) to the date and time of the first in angioedema attack after the first dose for the efficacy evaluation period of Day 0 through Day 182.

Measure: Time to First Angioedema Attack After Day 0 Through Day 182

Time: Day 0 Through Day 182

Description: The time to the first angioedema attack (days) after Day 0 for the efficacy evaluation period of Day 70 through Day 182 will be calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 70 through Day 182) to the date and time of the first in angioedema attack after the first dose for the efficacy evaluation period of Day 70 through Day 182.

Measure: Time to First Angioedema Attack After Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Efficacy evaluation period will consist of two periods: Day 0 (after study drug administration) through Day 182 (the end of treatment period), presumed steady-state period from Day 70 through Day 182. Run in period will be 4 weeks and may be extended up to 8 weeks to determine their baseline attack rate. The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period will be expressed as a monthly (28 days) angioedema attack rate. Number of participants achieving at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed normalized number of attacks per 4 weeks during each of the efficacy evaluation periods relative to the observation period NNA will be assessed.

Measure: Number of Participants Achieving at Least 50 %, 70%, 90% and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) per 4 Weeks during each of the Efficacy Evaluation Periods Relative to the Observation Period NNA

Time: Day 0 Through Day 182

Description: The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period will be expressed as a monthly (28 days) angioedema attack rate. Number of participants achieving normalized number of attacks < 1.0 per 4 weeks during each of the efficacy evaluation periods will be assessed.

Measure: Number of Participants Achieving Normalized Number of Attacks (NNA) Less than (<)1.0 per 4 weeks During Each of the Efficacy Evaluation Periods

Time: Day 0 Through Day 182, Day 70 through Day 182

Description: A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. A SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.

Measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs)

Time: From start of the study up to follow up (Day 196)

Description: Plasma Concentrations of lanadelumab will be assessed.

Measure: Plasma Concentrations of Lanadelumab

Time: Day 0, 4, 28, 56, 84, 112, 140, 168 and 182

Description: Plasma Kallikrein activity will be measured by biomarker cleaved high molecular weight kininogen (cHMWK ) level to assess pharmacodynamics of lanadelumab.

Measure: Plasma Kallikrein (pKal) Activity

Time: Day 0, 4, 28, 56, 84, 112, 140, 168 and 182

Description: Number of participants with neutralizing or non-neutralizing antidrug antibodies in plasma will be assessed.

Measure: Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma

Time: Day 0, 28, 56, 84, 112, 140, 168 and 182

Description: The AE-QoL questionnaire is a self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema. The AE-QoL consists of 17 disease-specific quality-of-life items, to produce a total AEQoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items has a five point response scale ranging from 1 (Never) to 5 (Very Often).

Measure: Change in Total Angioedema Quality of life (AE-QoL) Questionnaire Score During the Treatment Period of Day 0 Through Day 182

Time: Day 0 through Day 182


HPO Nodes