Clinical trial NCT05139810: OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
Official title: A Phase 3 Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ISIS 721744 in Patients With Hereditary Angioedema (HAE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema
Keywords: HAE
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-01
Enrollment: 91
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time-Normalized Investigator-Confirmed (IC) HAE Attack Rate (Per Month) From Week 1 to Week 25
timeFrame: Week 1 to Week 25
Secondary outcomes:
measure: Time-Normalized IC HAE Attack Rate (Per Month) From Week 5 to Week 25
timeFrame: Week 5 to Week 25
measure: Percentage of IC HAE Attack-Free Participants From Week 5 to Week 25
timeFrame: Week 5 to Week 25
measure: Time-Normalized Moderate or Severe IC HAE Attack Rate (Per Month) From Week 5 to Week 25
timeFrame: Week 5 to Week 25
measure: Number of Participants With a Clinical Response From Week 5 to Week 25
timeFrame: Week 5 to Week 25
measure: IC HAE Attack Rate Requiring Acute HAE Therapy From Week 5 to Week 25
timeFrame: Week 5 to Week 25
measure: Percentage of Participants Who Are Well Controlled on the Angioedema Control Test (AECT) at Week 25
timeFrame: Week 25
measure: Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Week 25
timeFrame: Week 25
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Ionis Investigative Site
state: Arizona
city: San Diego
country: United States
facility: Ionis Investigative Site
state: California
city: Santa Monica
country: United States
facility: Ionis Investigative Site
state: California
city: Walnut Creek
country: United States
facility: Ionis Investigative Site
state: California
city: Colorado Springs
country: United States
facility: Ionis Investigative Site
state: Colorado
city: Tampa
country: United States
facility: Ionis Investigative Site
state: Florida
city: Kansas City
country: United States
facility: Ionis Investigative Site
state: Kansas
city: Boston
country: United States
facility: Ionis Investigative Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Ionis Investigative Site
state: Michigan
city: Saint Louis
country: United States
facility: Ionis Investigative Site
state: Missouri
city: Columbus
country: United States
facility: Ionis Investigative Site
state: Ohio
city: Toledo
country: United States
facility: Ionis Investigative Site
state: Ohio
city: Hershey
country: United States
facility: Ionis Investigative Site
state: Pennsylvania
city: Dallas
country: United States
facility: Ionis Investigative Site
state: Texas
city: Murray
country: United States
facility: Ionis Investigative Site
state: Utah
city: Brussels
country: Belgium
facility: Ionis Investigative Site
city: Brussels
country: Belgium
facility: Ionis Investigative Site
city: Edegem
country: Belgium
facility: Ionis Investigative Site
city: Sofia
country: Bulgaria
facility: Ionis Investigative Site
city: Sofia
country: Bulgaria
facility: Ionis Investigative Site
city: Ottawa
country: Canada
facility: Ionis Investigative Site
state: Ontario
city: Edmonton
country: Canada
facility: Ionis Investigative Site
city: Odense
country: Denmark
facility: Ionis Investigative Site
city: La Tronche
country: France
facility: Ionis Investigative Site
city: Marseille
country: France
facility: Ionis Investigative Site
city: Paris
country: France
facility: Ionis Investigative Site
city: Berlin
country: Germany
facility: Ionis Investigative Site
city: Frankfurt
country: Germany
facility: Ionis Investigative Site
city: Munich
country: Germany
facility: Ionis Investigative Site
city: Ashkelon
country: Israel
facility: Ionis Investigative Site
city: Haifa
country: Israel
facility: Ionis Investigative Site
city: Tel Aviv
country: Israel
facility: Ionis Investigative Site
city: Catania
country: Italy
facility: Ionis Investigative Site
city: Milan
country: Italy
facility: Ionis Investigative Site
city: Napoli
country: Italy
facility: Ionis Investigative Site
city: Padova
country: Italy
facility: Ionis Investigative Site
city: Palermo
country: Italy
facility: Ionis Investigative Site
city: Amsterdam
country: Netherlands
facility: Ionis Investigative Site
city: Groningen
country: Netherlands
facility: Ionis Investigative Site
city: Kraków
country: Poland
facility: Ionis Investigative Site
city: Barcelona
country: Spain
facility: Ionis Investigative Site
city: Barcelona
country: Spain
facility: Ionis Investigative Site
city: Madrid
country: Spain
facility: Ionis Investigative Site
city: Sevilla
country: Spain
facility: Ionis Investigative Site
city: Valencia
country: Spain
facility: Ionis Investigative Site
city: Ankara
country: Turkey
facility: Ionis Investigative Site
city: Istanbul
country: Turkey
facility: Ionis Investigative Site
city: İzmir
country: Turkey
facility: Ionis Investigative Site
city: Birmingham
country: United Kingdom
facility: Ionis Investigative Site
city: Bristol
country: United Kingdom
facility: Ionis Investigative Site
city: London
country: United Kingdom
facility: Ionis Investigative Site
Study officials:
References:
citation: 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.