Clinical trial NCT02584959: Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1 Esterase Inhibitor for the Prevention of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Two-period, Three-sequence, Partial Crossover Study to Evaluate the Efficacy and Safety of Subcutaneous Administration of 2000 IU of C1 Esterase Inhibitor [Human] Liquid for Injection for the Prevention of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-10-23
Enrollment: 75
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the efficacy and safety of subcutaneous administration of a liquid formulation of C1 esterase inhibitor for the prevention of angioedema attacks in adolescent and adult subjects with hereditary angioedema.


Eligibility criteria: The maximum duration of participation is approximately 9 months. Patients will complete a screening period of up to 21 days. Following screening, eligible patients will be randomly assigned to 1 of 3 treatment sequences. Each patient will undergo 2 14-week treatment periods for a total of 28 weeks (Treatment Period 1 and Treatment Period 2). After completing the 2 treatment periods, patients will enter a 1-month follow-up period.

Primary outcomes:
measure: Time-Normalized Number of Attacks (NNA) for Participants During a Treatment Period
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
Secondary outcomes:
measure: Proportion of Participants Meeting at Least a 50% Reduction in NNA (Normalized Number of Angioedema Attacks) During the Experimental Injection Treatment Period Relative to the Placebo Period.
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Time-Normalized Number of Attacks (NNA) for Participants During Each Treatment Period Excluding the First 2 Weeks.
timeFrame: Weeks 3 to 14 for treatment period 1 and 2
measure: Proportion of Participants Meeting at Least a 50% Reduction in NNA (Normalized Number of Angioedema Attacks) During the Experimental Injection Treatment Period Relative to the Placebo Period Excluding the First 2 Weeks of Each Treatment Period.
timeFrame: Weeks 3 to 14 for treatment period 1 and 2
measure: Proportion of Participants Meeting at Least a 50% Reduction in NNA (Normalized Number of Angioedema Attacks) During the Experimental Injection Treatment Period Relative to the Pre-treatment Assessment.
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Cumulative Attack Severity
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Number of Attack-free Days
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Number of Angioedema Attacks Requiring Acute Treatment
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Response to Icatibant When Administered for an Acute Attack
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Number of Patients With Adverse Events (AEs)
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Number of Participants With Injection Site Reactions
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Number of Patients With Positive Anti-C1 INH Antibodies
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: PK Parameters: AUC (0-96) and AUC (0-t) for Functional C1 INH Binding Activity
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2. In addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: PK Parameters: AUC (0-96) and AUC (0-t) for C1 INH Antigen Concentrations
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2. In addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: PK Parameters: AUC (0-96) and AUC (0-t) for Complement C4 Concentrations (Treamtment C1 INH)
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2. In addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: PK Parameters: AUC (0-96) and AUC (0-t) for Complement C4 Concentrations (Treatment Placebo)
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2. In addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: PK Parameters: Cmax and Cmin for Functional C1 INH Binding Activity
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: PK Parameters: Cmax and Cmin for C1 INH Antigen Concentrations
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2
measure: PK Parameters: Cmax and Cmin for Complement C4 Concentrations (Treatment C1 INH)
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: PK Parameters: Cmax and Cmin for Complement C4 Concentrations (Treatment Placebo)
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: PK Parameters: Tmax
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: PK Parameters: Tmax for Complement C4 Concentrations (Placebo Group)
timeFrame: Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
measure: Assess Disease Activity as Measured by the Angioedema Activity Score (AAS) Normalized Per Month
timeFrame: Weeks 1 to 14 for treatment period 1 and 2
measure: Participant Experience With Self-administration: Overall Experience With the Syringe
timeFrame: Week 14 for treatment period 1 and 2
measure: Participant Experience With Self-administration: How Many Visits for Confidence With Self-administration
timeFrame: Week 14 for treatment period 1 and 2
measure: Participant Experience With Self-administration: Better Long-term Option and Preferred Administration
timeFrame: Week 14 for treatment period 1 and 2
measure: Mean Change in Angioedema Quality of Life Questionnaire Scores From Baseline to Week 13
timeFrame: Baseline to week 13 for treatment period 1 and 2
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Medical Research of Arizona
state: Arizona
city: Santa Monica
country: United States
facility: AIRE Medical of Los Angeles
state: California
city: Walnut Creek
country: United States
facility: Bay Area Allergy
state: California
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates PC
state: Colorado
city: Marietta
country: United States
facility: Atlanta Allergy and Asthma Clinic
state: Georgia
city: Chevy Chase
country: United States
facility: Institute For Asthma and Allergy
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Fair Lawn
country: United States
facility: Allergy Asthma and Immunology
state: New Jersey
city: Iselin
country: United States
facility: Allergy Treatment Center of New Jersey
state: New Jersey
city: Charlotte
country: United States
facility: Clinical Research of Charlotte
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center Inc
state: Ohio
city: Middleburg Heights
country: United States
facility: Clinical Research Solutions
state: Ohio
city: Tulsa
country: United States
facility: Allergy Clinic of Tulsa
state: Oklahoma
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Allergy Research Corporation
state: Ontario
city: Mörfelden-Walldorf
country: Germany
facility: Hämophilie Zentrum Rhein Main GmbH
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Targu Mures
country: Romania
facility: MediQuest Clinical Research Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
citation: Lumry WR, Martinez-Saguer I, Yang WH, Bernstein JA, Jacobs J, Moldovan D, Riedl MA, Johnston DT, Li HH, Tang Y, Schranz J, Lu P, Vardi M, Farkas H; SAHARA study group. Fixed-Dose Subcutaneous C1-Inhibitor Liquid for Prophylactic Treatment of C1-INH-HAE: SAHARA Randomized Study. J Allergy Clin Immunol Pract. 2019 May-Jun;7(5):1610-1618.e4. doi: 10.1016/j.jaip.2019.01.021. Epub 2019 Jan 23.