A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)

Hereditary Angioedema Clinical Trial

Official title:

An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05392114
• Other study ID #: ISIS 721744-CS7
• Secondary ID: 2022-000757-93
• Status: Recruiting
• Phase: Phase 3
• Start date: July 13, 2022
• Est. completion date: March 2027

Study information

• Verified date: June 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: Ionis Pharmaceuticals
• Phone: (844) 910-0878
• Email: ionisHAE2study[@]clinicaltrialmedia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the long-term safety and efficacy of donidalorsen in people with HAE and the effects of donidalorsen on the number of HAE attacks and their impact on quality of life (QoL).

Description:

This is a Phase 3, multi-center, open-label, global study with donidalorsen in up to approximately 144 participants with HAE-1 (Type I) and HAE-2 (Type II). There are two groups in this study: 1) participants who roll over from another study of donidalorsen (open-label extension [OLE] participants), and 2) new participants who are not rolling over from another study of donidalorsen and were previously maintained on HAE prophylactic therapy with lanadelumab, berotralstat, or a C1-esterase inhibitor (C1-INH). The length of participation in the study is approximately 70 weeks for OLE participants and 76 weeks for other participants. Participants will receive donidalorsen in an Extended Treatment Period for up to an additional 104 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: March 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria

1. Participants and, as applicable, legally authorized representatives (i.e., parent(s)/legal guardian), must provide written and signed informed consent form (ICF).

2. Participants must have access to, and the ability to use, = 1 acute medication(s) (e.g., plasma-derived or recombinant C1-INH concentrate or a bradykinin receptor (BK) 2-receptor antagonist) to treat angioedema attacks.

Open-Label Extension Participants ONLY:

3. Satisfactory completion of ISIS 721744-CS5 (randomized placebo-controlled index study) through Week 25 or participants who are allowed to exit ISIS 721744-CS5 study per protocol with an acceptable safety and tolerability profile.

New (not previously on donidalorsen) Participants ONLY:

4. Participants must be aged = 12 years at the time of informed consent and, as applicable, assent.

5. Participants must have a documented diagnosis of HAE-1/HAE-2.

6. Participants must be on a stable dose (= 12 weeks) of prophylaxis treatment with lanadelumab or berotralstat or SC C1-esterase inhibitor prior to the Screening Period.

Exclusion Criteria

Open-Label Extension Participants:

1. Have any new condition or worsening of an existing condition or change or anticipated change in medication.

New (not previously on donidalorsen) Participants ONLY:

2. 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).

3. Anticipated change in the use of concurrent androgen or tranexamic acid prophylaxis used to prevent angioedema attacks.

4. Any clinically-significant abnormalities in screening laboratory values.

5. Malignancy within 5 years of Screening, except for non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma that has been successfully treated.

6. Hypersensitivity to the active substance (donidalorsen) or to any of the excipients.

7. Treatment with another investigational drug (non-oligonucleotide) or biological agent within 1 month of Screening or 5 half-lives of investigational agent, whichever is longer.

8. Recent history of, or current drug or alcohol abuse.

9. Participated in a prior donidalorsen study.

10. Exposure to any of the following medications:

1. Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption.

2. 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.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• Donidalorsen
Donidalorsen will be administered by SC injection.

Locations

Country	Name	City	State
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
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	München
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
Italy	Ionis Investigative Site	San Donato Milanese
Netherlands	Ionis Investigative Site	Amsterdam
Netherlands	Ionis Investigative Site	Groningen
Poland	Ionis Investigative Site	Krakow
Puerto Rico	Ionis Investigative Site	San Juan
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	Altindag
Turkey	Ionis Investigative Site	Bornova
Turkey	Ionis Investigative Site	Istanbul
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	Cincinnati	Ohio
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	La Jolla	California
United States	Ionis Investigative Site	Mooresville	North Carolina
United States	Ionis Investigative Site	Murray	Utah
United States	Ionis Investigative Site	Paradise Valley	Arizona
United States	Ionis Investigative Site	Saint Louis	Missouri
United States	Ionis Investigative Site	Santa Monica	California
United States	Ionis Investigative Site	Tampa	Florida
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,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Puerto Rico,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity		Up to approximately 70 weeks, plus 104 weeks for Group 1; up to approximately 76 weeks, plus 104 weeks for Group 2
Secondary	Time-normalized Number of Investigator-confirmed HAE Attacks (per Month)		Week 1 to Week 157 for Group 1 and Group 2
Secondary	Percentage of Investigator-confirmed HAE Attack-free Participants		Week 1 to Week 157 for Group 1 and Group 2
Secondary	Time-normalized Number of Moderate or Severe Investigator-confirmed HAE Attacks (per Month)		Week 1 to Week 157 for Group 1 and Group 2
Secondary	Number of Investigator-confirmed HAE Attacks Requiring Acute Therapy		Week 1 to Week 157 for Group 1 and Group 2
Secondary	Angioedema Quality of Life (AE-QoL) Questionnaire Total Score	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.	Up to 157 weeks for Group 1 and Group 2