OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
A Phase 3 Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ISIS 721744 in Patients With Hereditary Angioedema (HAE)
2 other identifiers
interventional
91
14 countries
51
Brief Summary
The purpose of this study was 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Dec 2021
51 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
November 18, 2021
CompletedFirst Posted
Study publicly available on registry
December 1, 2021
CompletedStudy Start
First participant enrolled
December 3, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 9, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 9, 2023
CompletedResults Posted
Study results publicly available
March 6, 2025
CompletedMarch 6, 2025
February 1, 2025
1.9 years
November 18, 2021
February 13, 2025
February 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time-Normalized Investigator-Confirmed (IC) HAE Attack Rate (Per Month) From Week 1 to Week 25
The time-adjusted HAE attack rate was calculated as number of IC HAE attacks occurring from Week 1 to Week 25, divided by the number of days the participant contributed to the period multiplied by 28 days. An HAE attack was defined as an event with signs or symptoms consistent with an attack in at least 1 of the locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
Week 1 to Week 25
Secondary Outcomes (7)
Time-Normalized IC HAE Attack Rate (Per Month) From Week 5 to Week 25
Week 5 to Week 25
Percentage of IC HAE Attack-Free Participants From Week 5 to Week 25
Week 5 to Week 25
Time-Normalized Moderate or Severe IC HAE Attack Rate (Per Month) From Week 5 to Week 25
Week 5 to Week 25
Number of Participants With a Clinical Response From Week 5 to Week 25
Week 5 to Week 25
IC HAE Attack Rate Requiring Acute HAE Therapy From Week 5 to Week 25
Week 5 to Week 25
- +2 more secondary outcomes
Study Arms (3)
Pooled Placebo
PLACEBO COMPARATORParticipants with hereditary angioedema type I/type II (HAE-1/HAE-2) received placebo subcutaneously (SC) either every 4 weeks (Weeks 1, 5, 9, 13, 17, and 21) or 8 weeks (Weeks 1, 9, and 17)
Cohort A: Donidalorsen 80 mg
EXPERIMENTALParticipants with HAE-1/HAE-2 received donidalorsen, 80 mg, SC, every 4 weeks at Weeks 1, 5, 9, 13, 17, and 21.
Cohort B: Donidalorsen 80 mg
EXPERIMENTALParticipants with HAE-1/HAE-2 received donidalorsen, 80 mg, SC, every 8 weeks at Weeks 1, 9, and 17.
Interventions
Donidalorsen was administered by SC injection.
Donidalorsen-matching placebo was administered by SC injection.
Eligibility Criteria
You may qualify if:
- Participants, or their legally appointed and authorized representatives, must provide written and signed informed consent form (ICF)/assent
- Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent
- Participants must have a documented diagnosis of hereditary angioedema type 1 (HAE-1)/hereditary angioedema type 2 (HAE-2)
- Participants must:
- Experience a minimum of 2 HAE attacks (confirmed by the Investigator) during the Screening Period
- Be willing to complete the participant reported outcomes (PRO) assessments throughout the study
- Participants must have access to, and the ability to use acute medication(s) to treat angioedema attacks
You may not qualify if:
- 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)
- Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of Screening
- Participated in a prior ISIS 721744 study
- Exposure to any of the following medications:
- Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption within 4 weeks prior to Screening
- Chronic prophylaxis with Takhzyro, Haegarda, Cinryze and Ruconest or Orladeyo within 5 half-lives prior to Screening
- Recent history (3 years) of, or current drug or alcohol abuse
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (51)
Ionis Investigative Site
Scottsdale, Arizona, 85251, United States
Ionis Investigative Site
San Diego, California, 92122, United States
Ionis Investigative Site
Santa Monica, California, 90404, United States
Ionis Investigative Site
Walnut Creek, California, 94598, United States
Ionis Investigative Site
Colorado Springs, Colorado, 80907, United States
Ionis Investigative Site
Tampa, Florida, 33613, United States
Ionis Investigative Site
Kansas City, Kansas, 66205, United States
Ionis Investigative Site
Boston, Massachusetts, 02114, United States
Ionis Investigative Site
Ann Arbor, Michigan, 48109, United States
Ionis Investigative Site
St Louis, Missouri, 63110, United States
Ionis Investigative Site
Columbus, Ohio, 43235, United States
Ionis Investigative Site
Toledo, Ohio, 43617, 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
Brussels, 1020, Belgium
Ionis Investigative Site
Brussels, 1200, Belgium
Ionis Investigative Site
Edegem, 2650, Belgium
Ionis Investigative Site
Sofia, 1431, Bulgaria
Ionis Investigative Site
Sofia, 1680, Bulgaria
Ionis Investigative Site
Ottawa, Ontario, K1G6C6, Canada
Ionis Investigative Site
Edmonton, T6G 2G3, Canada
Ionis Investigative Site
Odense, 5000, Denmark
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
Munich, 81675, Germany
Ionis Investigative Site
Ashkelon, 78278, Israel
Ionis Investigative Site
Haifa, 3104802, Israel
Ionis Investigative Site
Tel Aviv, 6423906, Israel
Ionis Investigative Site
Catania, 95124, Italy
Ionis Investigative Site
Milan, 20138, Italy
Ionis Investigative Site
Napoli, 80131, Italy
Ionis Investigative Site
Padua, 35128, Italy
Ionis Investigative Site
Palermo, 90146, Italy
Ionis Investigative Site
Amsterdam, 1105 AZ, Netherlands
Ionis Investigative Site
Groningen, 9713 GZ, Netherlands
Ionis Investigative Site
Krakow, 31-503, Poland
Ionis Investigative Site
Barcelona, 08035, Spain
Ionis Investigative Site
Barcelona, 8907, Spain
Ionis Investigative Site
Madrid, 28046, Spain
Ionis Investigative Site
Seville, 41013, Spain
Ionis Investigative Site
Valencia, 46026, Spain
Ionis Investigative Site
Ankara, 6230, Turkey (Türkiye)
Ionis Investigative Site
Istanbul, 34093, Turkey (Türkiye)
Ionis Investigative Site
Izmir, 35100, Turkey (Türkiye)
Ionis Investigative Site
Birmingham, B9 5SS, United Kingdom
Ionis Investigative Site
Bristol, BS10 5NB, United Kingdom
Ionis Investigative Site
London, E1 1FR, United Kingdom
Related Publications (1)
Riedl MA, Tachdjian R, Lumry WR, Craig T, Karakaya G, Gelincik A, Stobiecki M, Jacobs JS, Gokmen NM, Reshef A, Gompels MM, Manning ME, Bordone L, Newman KB, Treadwell S, Wang S, Yarlas A, Cohn DM; OASIS-HAE Team. Efficacy and Safety of Donidalorsen for Hereditary Angioedema. N Engl J Med. 2024 Jul 4;391(1):21-31. doi: 10.1056/NEJMoa2402478. Epub 2024 May 31.
PMID: 38819395RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Ionis Pharmaceuticals, Inc.
- Organization
- Ionis Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
November 18, 2021
First Posted
December 1, 2021
Study Start
December 3, 2021
Primary Completion
November 9, 2023
Study Completion
November 9, 2023
Last Updated
March 6, 2025
Results First Posted
March 6, 2025
Record last verified: 2025-02
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/.