A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)

Phase 3

Recruiting

• Conditions: Hereditary Angioedema
• Interventions: Drug: Donidalorsen

• Registration Number: NCT05392114
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

The purpose of this study is to evaluate the long-term safety and efficacy of donidalorsen in people with HAE and the effects of donidalorsen on the number of HAE attacks and their impact on quality of life (QoL).

Detailed Description

This is a Phase 3, multi-center, open-label, global study with donidalorsen in up to approximately 144 participants with HAE-1 (Type I) and HAE-2 (Type II). There are two groups in this study: 1) participants who roll over from another study of donidalorsen (open-label extension \[OLE\] participants), and 2) new participants who are not rolling over from another study of donidalorsen and were previously maintained on HAE prophylactic therapy with lanadelumab, berotralstat, or a C1-esterase inhibitor (C1-INH). The length of participation in the study is approximately 70 weeks for OLE participants and 76 weeks for other participants. Participants will receive donidalorsen in an Extended Treatment Period for up to an additional 104 weeks.

Study Timeline

• Study First Submitted: 2022-05-23
• Study First Submitted QC: 2022-05-23
• Study First Posted: 2022-05-26
• Study Start: 2022-07-13
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-08
• Last Update Posted: 2024-11-12
• Primary Completion: 2026-12
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OLE Participants	Donidalorsen	Group 1 and Group 2 participants will be administered donidalorsen by SC injection for up to 157 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity	Up to approximately 70 weeks, plus 104 weeks for Group 1; up to approximately 76 weeks, plus 104 weeks for Group 2

Secondary Outcome Measures

Name	Time	Method
Time-normalized Number of Investigator-confirmed HAE Attacks (per Month)	Week 1 to Week 157 for Group 1 and Group 2
Percentage of Investigator-confirmed HAE Attack-free Participants	Week 1 to Week 157 for Group 1 and Group 2
Time-normalized Number of Moderate or Severe Investigator-confirmed HAE Attacks (per Month)	Week 1 to Week 157 for Group 1 and Group 2
Number of Investigator-confirmed HAE Attacks Requiring Acute Therapy	Week 1 to Week 157 for Group 1 and Group 2
Angioedema Quality of Life (AE-QoL) Questionnaire Total Score	Up to 157 weeks for Group 1 and Group 2	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