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)

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).

This was a Phase 3, multi-center, double-blind, randomized, placebo-controlled study of donidalorsen in 91 participants. Participants were randomly assigned 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 were randomized in a 3:1 ratio to receive donidalorsen or matching-placebo. The study included an up to 8-week Screening Period, a 24-week Treatment Period, and an up to 13-week Post-treatment Period.

Key Inclusion Criteria

1. 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

Key Exclusion Criteria

1. 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