OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
Purpose
The purpose of this study is 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).
Condition
- Hereditary Angioedema
Eligibility
- Eligible Ages
- Over 12 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Participants, or their legally appointed and authorized representatives, must provide written and signed informed consent form (ICF)/assent 2. Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent 3. Participants must have a documented diagnosis of hereditary angioedema type 1 (HAE-1)/hereditary angioedema type 2 (HAE-2) 4. Participants must: 1. Experience a minimum of 2 HAE attacks (confirmed by the Investigator) during the Screening Period 2. Be willing to complete the participant reported outcomes (PRO) assessments throughout the study 5. Participants must have access to, and the ability to use acute medication(s) to treat angioedema attacks
Exclusion Criteria
- 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) 2. Any clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the study 3. Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of Screening 4. Participated in a prior ISIS 721744 study 5. Exposure to any of the following medications: 1. Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption within 4 weeks prior to Screening 2. Chronic prophylaxis with Takhzyro, Haegarda, Cinryze and Ruconest or Orladeyo within 5 half-lives prior to Screening 3. 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 6. Recent history (3 years) of, or current drug or alcohol abuse
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Donidalorsen: Cohort A |
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks. |
|
|
Experimental Donidalorsen: Cohort B |
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks. |
|
|
Placebo Comparator Placebo: Cohort A |
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks. |
|
|
Placebo Comparator Placebo: Cohort B |
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks. |
|
More Details
- Status
- Completed
- Sponsor
- Ionis Pharmaceuticals, Inc.
Study Contact
Detailed Description
This is a Phase 3, multi-center, double-blind, randomized, placebo-controlled study of donidalorsen in up to 84 participants. Participants will be randomized in a 2:1 ratio to Cohort A (donidalorsen or placebo every 4 weeks) or Cohort B (donidalorsen or placebo every 8 weeks), respectively. Within each Cohort, participants will be randomized in a 3:1 ratio to receive donidalorsen or matching-placebo. The length of participation in the study is approximately 11 months, which includes an up to 8-week Screening Period, a 25-week Treatment Period, and an up to 13-week Post-treatment Period.