A Phase 3 Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ISIS 721744 in Patients With Hereditary Angioedema (HAE)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Enrollment
- 91
- Locations
- 1
- Primary Endpoint
- Time-Normalized Investigator-Confirmed (IC) HAE Attack Rate (Per Month) From Week 1 to Week 25
Study Overview
Brief Summary
The purpose of this study was to evaluate the safety and efficacy of donidalorsen in participants with HAE and effect of donidalorsen on the quality and pattern of HAE attacks and their impact on quality of life (QoL).
Detailed Description
This was a Phase 3, multi-center, double-blind, randomized, placebo-controlled study of donidalorsen in 91 participants. Participants were randomly assigned in a 2:1 ratio to Cohort A (donidalorsen or placebo every 4 weeks) or Cohort B (donidalorsen or placebo every 8 weeks), respectively. Within each Cohort, participants were randomized in a 3:1 ratio to receive donidalorsen or matching-placebo. The study included an up to 8-week Screening Period, a 24-week Treatment Period, and an up to 13-week Post-treatment Period.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Pooled Placebo
Participants with hereditary angioedema type I/type II (HAE-1/HAE-2) received placebo subcutaneously (SC) either every 4 weeks (Weeks 1, 5, 9, 13, 17, and 21) or 8 weeks (Weeks 1, 9, and 17)
Intervention: Donidalorsen (Drug)
Cohort A: Donidalorsen 80 mg
Participants with HAE-1/HAE-2 received donidalorsen, 80 mg, SC, every 4 weeks at Weeks 1, 5, 9, 13, 17, and 21.
Intervention: Donidalorsen (Drug)
Cohort B: Donidalorsen 80 mg
Participants with HAE-1/HAE-2 received donidalorsen, 80 mg, SC, every 8 weeks at Weeks 1, 9, and 17.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Time-Normalized Investigator-Confirmed (IC) HAE Attack Rate (Per Month) From Week 1 to Week 25
Time Frame: Week 1 to Week 25
The time-adjusted HAE attack rate was calculated as number of IC HAE attacks occurring from Week 1 to Week 25, divided by the number of days the participant contributed to the period multiplied by 28 days. An HAE attack was defined as an event with signs or symptoms consistent with an attack in at least 1 of the 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).
Secondary Outcomes
- Time-Normalized IC HAE Attack Rate (Per Month) From Week 5 to Week 25(Week 5 to Week 25)
- Percentage of IC HAE Attack-Free Participants From Week 5 to Week 25(Week 5 to Week 25)
- Time-Normalized Moderate or Severe IC HAE Attack Rate (Per Month) From Week 5 to Week 25(Week 5 to Week 25)
- Number of Participants With a Clinical Response From Week 5 to Week 25(Week 5 to Week 25)
- IC HAE Attack Rate Requiring Acute HAE Therapy From Week 5 to Week 25(Week 5 to Week 25)
- Percentage of Participants Who Are Well Controlled on the Angioedema Control Test (AECT) at Week 25(Week 25)
- Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Week 25(Week 25)