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Long-term safety and efficacy of donidalorsen for treating hereditary angioedema

An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)

Phase 3 Interventional Ionis Pharmaceuticals, Inc. · NCT05392114

This study is testing a new treatment called donidalorsen to see if it can safely reduce the number of attacks and improve the quality of life for people with hereditary angioedema.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment144 (estimated)
Ages12 Years and up
SexAll
SponsorIonis Pharmaceuticals, Inc. Industry-sponsored
Drugs / interventionslanadelumab
Locations50 sites (Paradise Valley, Arizona and 49 other locations)
Trial IDNCT05392114 on ClinicalTrials.gov

What this trial studies

This Phase 3, multi-center, open-label study evaluates the long-term safety and efficacy of donidalorsen in individuals with hereditary angioedema (HAE). The study includes approximately 144 participants, divided into two groups: those rolling over from a previous study and new participants who have been on other prophylactic therapies. Participants will receive donidalorsen for an extended treatment period, with the study lasting up to 76 weeks for new participants and 70 weeks for those in the open-label extension. The primary focus is on the frequency of HAE attacks and their impact on quality of life.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 12 years and older with a documented diagnosis of HAE-1 or HAE-2 who have been on stable prophylactic treatment.

Not a fit: Patients who are not diagnosed with hereditary angioedema or those who cannot access acute medications for angioedema attacks may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the frequency of HAE attacks and improve the quality of life for patients.

How similar studies have performed: Other studies have shown promise in using similar approaches for treating hereditary angioedema, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria

1. Participants and, as applicable, legally authorized representatives (i.e., parent(s)/legal guardian), must provide written and signed informed consent form (ICF).
2. 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:
3. 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:
4. Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent.
5. Participants must have a documented diagnosis of HAE-1/HAE-2.
6. Participants must be on a stable dose (≥ 12 weeks) of prophylaxis treatment with lanadelumab or berotralstat or SC C1-esterase inhibitor prior to the Screening Period.

Exclusion Criteria

Open-Label Extension Participants:

1. Have any new condition or worsening of an existing condition or change or anticipated change in medication.

   New (not previously on donidalorsen) Participants ONLY:
2. Concurrent diagnosis of any other type of recurrent angioedema, including acquired, idiopathic angioedema or HAE with normal C1-INH (also known as HAE Type III).
3. Anticipated change in the use of concurrent androgen or tranexamic acid prophylaxis used to prevent angioedema attacks.
4. Any clinically-significant abnormalities in screening laboratory values.
5. Malignancy within 5 years of Screening, except for non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma that has been successfully treated.
6. Hypersensitivity to the active substance (donidalorsen) or to any of the excipients.
7. Treatment with another investigational drug (non-oligonucleotide) or biological agent within 1 month of Screening or 5 half-lives of investigational agent, whichever is longer.
8. Recent history of, or current drug or alcohol abuse.
9. Participated in a prior donidalorsen study.
10. Exposure to any of the following medications:

    1. Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption.
    2. Oligonucleotides (including small interfering ribonucleic acid \[siRNA\]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received. This exclusion does not apply to vaccines.

Where this trial is running

Paradise Valley, Arizona and 49 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Hereditary AngioedemaHAE
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.