OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)

Phase 3

Completed

• Conditions: Hereditary Angioedema
• Interventions: Drug: Donidalorsen; Drug: Placebo

• Registration Number: NCT05139810
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

The purpose of this study is 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 is a Phase 3, multi-center, double-blind, randomized, placebo-controlled study of donidalorsen in up to 84 participants. Participants will be randomized 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 will be randomized in a 3:1 ratio to receive donidalorsen or matching-placebo. The length of participation in the study is approximately 11 months, which includes an up to 8-week Screening Period, a 25-week Treatment Period, and an up to 13-week Post-treatment Period.

Study Timeline

• Study First Submitted: 2021-11-18
• Study First Submitted QC: 2021-11-18
• Study First Posted: 2021-12-01
• Study Start: 2021-12-03
• Primary Completion: 2023-11-06
• Study Completion: 2023-11-09
• Disposition First Posted: 2024-06-18
• Status Verified: 2024-10
• Disposition First Submitted: 2024-10-07
• Last Update Submitted: 2024-10-07
• Last Update Posted: 2024-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 91

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Donidalorsen: Cohort A	Donidalorsen	Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
Donidalorsen: Cohort B	Donidalorsen	Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
Placebo: Cohort A	Placebo	Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
Placebo: Cohort B	Placebo	Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.

Primary Outcome Measures

Name	Time	Method
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 1 to Week 25	Week 1 to Week 25

Secondary Outcome Measures

Name	Time	Method
Time-Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25	Week 5 to Week 25
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25	Week 5 to Week 25
Percentage of Investigator-Confirmed HAE Attack-Free Participants 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	The AECT is a validated participant-reported outcome instrument to assess disease activity in participants with recurrent angioedema. The questionnaire consists of four questions asking about the frequency and severity of angioedema experienced in the prior month. Each question has 5 response choices. The AECT can be used to identify participants with poorly controlled disease by working with a cutoff value of greater than or equal to 10 points. Participants who score less than 10 points (0-9) in the AECT have poorly controlled disease whereas participants with controlled disease score 10-16 points. Higher scores will indicate well controlled disease.
Number of Participants With a Clinical Response Defined as a ≥ 50%, ≥ 70%, or ≥ 90% Reduction From Baseline (Screening Rate) in Investigator-confirmed HAE Attack Rate Between Week 5 to Week 25	Week 5 to Week 25
Number of Investigator-Confirmed HAE Attacks Requiring Acute HAE Therapy From Week 5 to Week 25	Week 5 to Week 25
Change in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Week 25	Week 25	The AE-QoL questionnaire is a validated tool to assess symptom-specific health-related QOL impairment in participants suffering from recurrent angioedema. The AE-QoL is a self-administered questionnaire comprising 17 questions across 4 domains: functioning, fatigue/mood, fears/shame, and food. The responses are scored from 1 to 5 where, 1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = very often. Total and domain scores range from 0 to 100, with higher scores indicating greater impairment.

Trial Locations

Locations (1)

Ionis Investigative Site; 🇬🇧 London, United Kingdom