Phase 3
N=91
OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
Hereditary Angioedema
Bottom Line
View on ClinicalTrials.gov: NCT05139810 ↗Enrolled (actual)
91
Serious AEs
1.1%
Results posted
Mar 2025
Primary outcome: Primary: Time-Normalized Investigator-Confirmed (IC) HAE Attack Rate (Per Month) From Week 1 to Week 25 — 2.26; 0.44; 1.02 HAE attacks per month — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Donidalorsen (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Primary completion
- Nov 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time-Normalized Investigator-Confirmed (IC) HAE Attack Rate (Per Month) From Week 1 to Week 25 |
2.26; 0.44; 1.02 | <0.001 sig |
| SECONDARY Time-Normalized IC HAE Attack Rate (Per Month) From Week 5 to Week 25 |
2.25; 0.30; 0.90 | <0.001 sig |
| SECONDARY Percentage of IC HAE Attack-Free Participants From Week 5 to Week 25 |
9.1; 53.3; 34.8 | =0.003 sig |
| SECONDARY Time-Normalized Moderate or Severe IC HAE Attack Rate (Per Month) From Week 5 to Week 25 |
1.15; 0.12; 0.68 | <0.001 sig |
| SECONDARY Number of Participants With a Clinical Response From Week 5 to Week 25 |
6; 42; 19; 4; 37; 15 | <0.001 sig |
| SECONDARY IC HAE Attack Rate Requiring Acute HAE Therapy From Week 5 to Week 25 |
1.80; 0.15; 0.59 | <0.001 sig |
| SECONDARY Percentage of Participants Who Are Well Controlled on the Angioedema Control Test (AECT) at Week 25 |
47.1; 92.9; 77.3 | — |
| SECONDARY Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Week 25 |
-6.19; -24.76; -19.85 | <0.001 sig |
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).
Eligibility Criteria
Key Inclusion Criteria
- 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
Key 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)
- Any clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the study
- 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
- 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
- Recent history (3 years) of, or current drug or alcohol abuse
Data sourced from ClinicalTrials.gov (NCT05139810). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.