A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
2 other identifiers
interventional
154
14 countries
50
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jul 2022
Longer than P75 for phase_3
50 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 23, 2022
CompletedFirst Posted
Study publicly available on registry
May 26, 2022
CompletedStudy Start
First participant enrolled
July 13, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
December 12, 2025
December 1, 2025
4.4 years
May 23, 2022
December 5, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (5)
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
Study Arms (1)
OLE Participants
EXPERIMENTALGroup 1 and Group 2 participants will be administered donidalorsen by SC injection for up to 157 weeks.
Interventions
Donidalorsen will be administered by SC injection.
Eligibility Criteria
You may qualify if:
- Participants and, as applicable, legally authorized representatives (i.e., parent(s)/legal guardian), must provide written and signed informed consent form (ICF).
- 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:
- Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent.
- Participants must have a documented diagnosis of HAE-1/HAE-2.
- 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.
You may not qualify if:
- 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:
- 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).
- Anticipated change in the use of concurrent androgen or tranexamic acid prophylaxis used to prevent angioedema attacks.
- Any clinically-significant abnormalities in screening laboratory values.
- 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.
- Hypersensitivity to the active substance (donidalorsen) or to any of the excipients.
- 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.
- Recent history of, or current drug or alcohol abuse.
- Participated in a prior donidalorsen study.
- Exposure to any of the following medications:
- Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (50)
Ionis Investigative Site
Paradise Valley, Arizona, 85253, United States
Ionis Investigative Site
La Jolla, California, 92037, United States
Ionis Investigative Site
Santa Monica, California, 90404, United States
Ionis Investigative Site
Walnut Creek, California, 94598, United States
Ionis Investigative Site
Tampa, Florida, 33613, United States
Ionis Investigative Site
Kansas City, Kansas, 66103, United States
Ionis Investigative Site
Boston, Massachusetts, 02114, United States
Ionis Investigative Site
Ann Arbor, Michigan, 48109, United States
Ionis Investigative Site
Detroit, Michigan, 48202, United States
Ionis Investigative Site
St Louis, Missouri, 63141, United States
Ionis Investigative Site
Mooresville, North Carolina, 28117, United States
Ionis Investigative Site
Cincinnati, Ohio, 45236, United States
Ionis Investigative Site
Columbus, Ohio, 43235, United States
Ionis Investigative Site
Hershey, Pennsylvania, 17033, United States
Ionis Investigative Site
Dallas, Texas, 75231, United States
Ionis Investigative Site
Murray, Utah, 84107, United States
Ionis Investigative Site
Edegem, 2650, Belgium
Ionis Investigative Site
Sofia, 1431, Bulgaria
Ionis Investigative Site
Sofia, 1680, Bulgaria
Ionis Investigative Site
Ottawa, Ontario, K1H 1E4, Canada
Ionis Investigative Site
Edmonton, AB T6G 1Z1, Canada
Ionis Investigative Site
La Tronche, 38700, France
Ionis Investigative Site
Marseille, 13385, France
Ionis Investigative Site
Paris, 75012, France
Ionis Investigative Site
Berlin, 12203, Germany
Ionis Investigative Site
Frankfurt, 60590, Germany
Ionis Investigative Site
München, 81675, Germany
Ionis Investigative Site
Ashkelon, 7830604, Israel
Ionis Investigative Site
Haifa, 3104802, Israel
Ionis Investigative Site
Tel Aviv, 6423906, Israel
Ionis Investigative Site
Catania, 95123, Italy
Ionis Investigative Site
Naples, 80131, Italy
Ionis Investigative Site
Padua, 35128, Italy
Ionis Investigative Site
Palermo, 90146, Italy
Ionis Investigative Site
San Donato Milanese, 20097, Italy
Ionis Investigative Site
Amsterdam, 1105, Netherlands
Ionis Investigative Site
Groningen, 9713 AP, Netherlands
Ionis Investigative Site
Krakow, 31-501, Poland
Ionis Investigative Site
San Juan, PR 00927, Puerto Rico
Ionis Investigative Site
Barcelona, 08035, Spain
Ionis Investigative Site
Barcelona, 08907, Spain
Ionis Investigative Site
Madrid, 28046, Spain
Ionis Investigative Site
Seville, 41013, Spain
Ionis Investigative Site
Valencia, 46026, Spain
Ionis Investigative Site
Altındağ, 06230, Turkey (Türkiye)
Ionis Investigative Site
Bornova, 35100, Turkey (Türkiye)
Ionis Investigative Site
Istanbul, 34093, Turkey (Türkiye)
Ionis Investigative Site
Birmingham, B9 5SS, United Kingdom
Ionis Investigative Site
Bristol, BS10 5NB, United Kingdom
Ionis Investigative Site
London, E1 2ES, United Kingdom
Related Publications (2)
Lumry WR, Tachdjian R, Craig T, Karakaya G, Gelincik A, Stobiecki M, Jacobs JS, Gokmen NM, Reshef A, Manning ME, Grammatikos A, Giardino F, Guilarte M, Baptist AP, Bordone L, Newman KB, Treadwell S, Lin T, Yarlas A, Riedl MA, Cohn DM. Donidalorsen for Long-Term Prophylaxis of Hereditary Angioedema Attacks: Results from the OASISplus Open-Label Extension Cohort at Year 1. J Asthma Allergy. 2026 Feb 23;19:592079. doi: 10.2147/JAA.S592079. eCollection 2026.
PMID: 41767175DERIVEDRiedl MA, Bernstein JA, Jacobs JS, Craig T, Banerji A, Perego F, Lumry WR, Wedner HJ, Gierer S, Manning ME, Bordone L, Treadwell S, Lin T, Newman KB, Yarlas A, Cohn DM. Donidalorsen Treatment of Hereditary Angioedema in Patients Previously on Long-Term Prophylaxis. J Allergy Clin Immunol Pract. 2025 Sep;13(9):2381-2389.e3. doi: 10.1016/j.jaip.2025.06.018. Epub 2025 Jul 17.
PMID: 40673861DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
May 23, 2022
First Posted
May 26, 2022
Study Start
July 13, 2022
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
March 1, 2027
Last Updated
December 12, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
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/.