A Phase 3 interventional study of Donidalorsen in Hereditary Angioedema, sponsored by Ionis Pharmaceuticals, Inc.. Active, not recruiting at 50 sites in 14 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2025-12-12.
Sponsored by Ionis Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment
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).
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.
171 studies on the registry are indexed under Angioedemas, Hereditary; 25 are open to participants now.
This study's enrollment of 154 is above the median of 53 across 115 interventional studies indexed under Angioedemas, Hereditary.
Browse Angioedemas, Hereditary studies →Ionis Pharmaceuticals, Inc. is the lead sponsor of 116 studies on the registry; 10 are open to participants now.
Of its 48 completed or terminated interventional studies of FDA-regulated products, 21 (44%) have results posted.
Counted across the registry records on this site, refreshed daily.
Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1-INH concentrate or a bradykinin receptor (BK) 2-receptor antagonist) to treat angioedema attacks.
Open-Label Extension Participants ONLY:
Satisfactory completion of ISIS 721744-CS5 (randomized placebo-controlled index study) through Week 25 or participants who are allowed to exit ISIS 721744-CS5 study per protocol with an acceptable safety and tolerability profile.
New (not previously on donidalorsen) Participants ONLY:
Exclusion Criteria
Open-Label Extension Participants:
Have any new condition or worsening of an existing condition or change or anticipated change in medication.
New (not previously on donidalorsen) Participants ONLY:
Exposure to any of the following medications:
Group 1 and Group 2 participants will be administered donidalorsen by SC injection for up to 157 weeks.
Drug: Donidalorsen
Donidalorsen will be administered by SC injection.
Also known as: ISIS 721744, IONIS-PKK-LRx
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity
Time frame: Up to approximately 70 weeks, plus 104 weeks for Group 1; up to approximately 76 weeks, plus 104 weeks for Group 2
Time-normalized Number of Investigator-confirmed HAE Attacks (per Month)
Time frame: Week 1 to Week 157 for Group 1 and Group 2
Percentage of Investigator-confirmed HAE Attack-free Participants
Time frame: Week 1 to Week 157 for Group 1 and Group 2
Time-normalized Number of Moderate or Severe Investigator-confirmed HAE Attacks (per Month)
Time frame: Week 1 to Week 157 for Group 1 and Group 2
Number of Investigator-confirmed HAE Attacks Requiring Acute Therapy
Time frame: Week 1 to Week 157 for Group 1 and Group 2
Angioedema Quality of Life (AE-QoL) Questionnaire Total Score
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.
Time frame: Up to 157 weeks for Group 1 and Group 2
Plan to share: Yes — Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
This study is active, not recruiting, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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Ionis Pharmaceuticals, Inc.