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

简要总结

主要结局

次要结局

• Time-Normalized Number of Attacks (NNA) for Participants During Each Treatment Period Excluding the First 2 Weeks.(Weeks 3 to 14 for treatment period 1 and 2)
• 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.(Weeks 1 to 14 for treatment period 1 and 2)
• Cumulative Attack Severity(Weeks 1 to 14 for treatment period 1 and 2)
• 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.(Weeks 1 to 14 for treatment period 1 and 2)
• Number of Patients With Positive Anti-C1 INH Antibodies(Weeks 1 to 14 for treatment period 1 and 2)
• 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.(Weeks 3 to 14 for treatment period 1 and 2)
• Number of Attack-free Days(Weeks 1 to 14 for treatment period 1 and 2)
• Number of Angioedema Attacks Requiring Acute Treatment(Weeks 1 to 14 for treatment period 1 and 2)
• Response to Icatibant When Administered for an Acute Attack(Weeks 1 to 14 for treatment period 1 and 2)
• Number of Patients With Adverse Events (AEs)(Weeks 1 to 14 for treatment period 1 and 2)
• Number of Participants With Injection Site Reactions(Weeks 1 to 14 for treatment period 1 and 2)
• PK Parameters: AUC (0-96) and AUC (0-t) for Functional C1 INH Binding Activity(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.)
• Assess Disease Activity as Measured by the Angioedema Activity Score (AAS) Normalized Per Month(Weeks 1 to 14 for treatment period 1 and 2)
• Participant Experience With Self-administration: How Many Visits for Confidence With Self-administration(Week 14 for treatment period 1 and 2)
• Participant Experience With Self-administration: Better Long-term Option and Preferred Administration(Week 14 for treatment period 1 and 2)
• Mean Change in Angioedema Quality of Life Questionnaire Scores From Baseline to Week 13(Baseline to week 13 for treatment period 1 and 2)
• PK Parameters: AUC (0-96) and AUC (0-t) for C1 INH Antigen Concentrations(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.)
• PK Parameters: AUC (0-96) and AUC (0-t) for Complement C4 Concentrations (Treamtment C1 INH)(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.)
• PK Parameters: AUC (0-96) and AUC (0-t) for Complement C4 Concentrations (Treatment Placebo)(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.)
• PK Parameters: Cmax and Cmin for Functional C1 INH Binding Activity(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.)
• PK Parameters: Cmax and Cmin for C1 INH Antigen Concentrations(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)
• PK Parameters: Cmax and Cmin for Complement C4 Concentrations (Treatment C1 INH)(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.)
• PK Parameters: Cmax and Cmin for Complement C4 Concentrations (Treatment Placebo)(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.)
• PK Parameters: Tmax(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.)
• PK Parameters: Tmax for Complement C4 Concentrations (Placebo Group)(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.)
• Participant Experience With Self-administration: Overall Experience With the Syringe(Week 14 for treatment period 1 and 2)