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 Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05139810
• Other study ID #: ISIS 721744-CS5
• Secondary ID: 2021-002571-19
• Status: Completed
• Phase: Phase 3
• Start date: December 3, 2021
• Est. completion date: November 9, 2023

Study information

• Verified date: December 2023
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: November 9, 2023
• Est. primary completion date: November 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• Donidalorsen
Donidalorsen will be administered by SC injection.
• Placebo
Donidalorsen-matching placebo will be administered by SC injection.

Locations

Country	Name	City	State
Belgium	Ionis Investigative Site	Brussels
Belgium	Ionis Investigative Site	Brussels
Belgium	Ionis Investigative Site	Edegem
Bulgaria	Ionis Investigative Site	Sofia
Bulgaria	Ionis Investigative Site	Sofia
Canada	Ionis Investigative Site	Edmonton
Canada	Ionis Investigative Site	Ottawa	Ontario
Denmark	Ionis Investigative Site	Odense
France	Ionis Investigative Site	La Tronche
France	Ionis Investigative Site	Marseille
France	Ionis Investigative Site	Paris
Germany	Ionis Investigative Site	Berlin
Germany	Ionis Investigative Site	Frankfurt
Germany	Ionis Investigative Site	Munich
Israel	Ionis Investigative Site	Ashkelon
Israel	Ionis Investigative Site	Haifa
Israel	Ionis Investigative Site	Tel Aviv
Italy	Ionis Investigative Site	Catania
Italy	Ionis Investigative Site	Milan
Italy	Ionis Investigative Site	Napoli
Italy	Ionis Investigative Site	Padova
Italy	Ionis Investigative Site	Palermo
Netherlands	Ionis Investigative Site	Amsterdam
Netherlands	Ionis Investigative Site	Groningen
Poland	Ionis Investigative Site	Kraków
Spain	Ionis Investigative Site	Barcelona
Spain	Ionis Investigative Site	Barcelona
Spain	Ionis Investigative Site	Madrid
Spain	Ionis Investigative Site	Sevilla
Spain	Ionis Investigative Site	Valencia
Turkey	Ionis Investigative Site	Ankara
Turkey	Ionis Investigative Site	Istanbul
Turkey	Ionis Investigative Site	Izmir
United Kingdom	Ionis Investigative Site	Birmingham
United Kingdom	Ionis Investigative Site	Bristol
United Kingdom	Ionis Investigative Site	London
United States	Ionis Investigative Site	Ann Arbor	Michigan
United States	Ionis Investigative Site	Boston	Massachusetts
United States	Ionis Investigative Site	Colorado Springs	Colorado
United States	Ionis Investigative Site	Columbus	Ohio
United States	Ionis Investigative Site	Dallas	Texas
United States	Ionis Investigative Site	Hershey	Pennsylvania
United States	Ionis Investigative Site	Kansas City	Kansas
United States	Ionis Investigative Site	Murray	Utah
United States	Ionis Investigative Site	Saint Louis	Missouri
United States	Ionis Investigative Site	San Diego	California
United States	Ionis Investigative Site	Santa Monica	California
United States	Ionis Investigative Site	Scottsdale	Arizona
United States	Ionis Investigative Site	Tampa	Florida
United States	Ionis Investigative Site	Toledo	Ohio
United States	Ionis Investigative Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Denmark,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 1 to Week 25		Week 1 to Week 25
Secondary	Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25		Week 5 to Week 25
Secondary	Percentage of Investigator-Confirmed HAE Attack-Free Participants From Week 5 to Week 25		Week 5 to Week 25
Secondary	Time-Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25		Week 5 to Week 25
Secondary	Number of Participants With a Clinical Response Defined as a = 50%, = 70%, or = 90% Reduction From Baseline (Screening Rate) in Investigator-confirmed HAE Attack Rate Between Week 5 to Week 25		Week 5 to Week 25
Secondary	Number of Investigator-Confirmed HAE Attacks Requiring Acute HAE Therapy From Week 5 to Week 25		Week 5 to Week 25
Secondary	Percentage of Participants who are Well Controlled on the Angioedema Control Test (AECT) at Week 25	The AECT is a validated participant-reported outcome instrument to assess disease activity in participants with recurrent angioedema. The questionnaire consists of four questions asking about the frequency and severity of angioedema experienced in the prior month. Each question has 5 response choices. The AECT can be used to identify participants with poorly controlled disease by working with a cutoff value of greater than or equal to 10 points. Participants who score less than 10 points (0-9) in the AECT have poorly controlled disease whereas participants with controlled disease score 10-16 points. Higher scores will indicate well controlled disease.	Week 25
Secondary	Change in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Week 25	The AE-QoL questionnaire is a validated tool to assess symptom-specific health-related QOL impairment in participants suffering from recurrent angioedema. The AE-QoL is a self-administered questionnaire comprising 17 questions across 4 domains: functioning, fatigue/mood, fears/shame, and food. The responses are scored from 1 to 5 where, 1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = very often. Total and domain scores range from 0 to 100, with higher scores indicating greater impairment.	Week 25