An Extension Study of Donidalorsen (IONIS-PKK-LRx) in Participants With Hereditary Angioedema

Hereditary Angioedema Clinical Trial

Official title:

An Open-Label Extension Study of ISIS 721744 in Patients With Hereditary Angioedema

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04307381
• Other study ID #: ISIS 721744-CS3
• Secondary ID: 2020-000197-14
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 1, 2020
• Est. completion date: April 2025

Study information

• Verified date: June 2024
• 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 extended dosing of donidalorsen administered subcutaneously (SC), with alternative dosing and/or dose frequency with donidalorsen in participants with hereditary angioedema (HAE).

Description:

This is an open-label extension study of donidalorsen in up to 24 participants with HAE. The length of participation in the study is approximately 68 weeks, which includes an up to 4-week qualification period, a 52-week treatment period, and a 12-week post-treatment period. Following the Week 53 treatment period visit, participants will receive donidalorsen in an extended treatment period for up to an additional 156 weeks. Participants taking part in the extended treatment period will enter the 12-week post-treatment period after completion of, or early termination from, the extended treatment period.

This study was extended to allow participants to receive donidalorsen for an additional 156 weeks following the initial 53-week treatment period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Satisfactory completion of ISIS 721744-CS2 (index study) through Week 17 with an acceptable safety and tolerability profile, per Sponsor and Investigator judgement

2. Able and willing to participate in a 64-week study

3. Females must be non-pregnant, non-lactating and either surgically sterile or post-menopausal

4. Males must be surgically sterile or abstinent* or if engaged in sexual relations with a female of child-bearing potential, participant is utilizing an acceptable contraceptive method

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

Exclusion Criteria:

1. Have any new condition or worsening of an existing condition or change or anticipated change in medication, which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• Donidalorsen
Donidalorsen administered SC

Locations

Country	Name	City	State
Netherlands	Ionis Investigative Site	Amsterdam
United States	Ionis Investigative Site	Cincinnati	Ohio
United States	Ionis Investigative Site	Dallas	Texas
United States	Ionis Investigative Site	Hershey	Pennsylvania
United States	Ionis Investigative Site	Plymouth	Minnesota
United States	Ionis Investigative Site	Santa Monica	California
United States	Ionis Investigative Site	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Netherlands, 

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 Week 221
Secondary	The Time-normalized HAE Attacks (per Month) by Treatment		Up to Week 221
Secondary	Plasma Prekallikrein (PKK) Levels		Up to Week 221
Secondary	Consumption of On-demand Medications		Up to Week 221
Secondary	Angioedema Quality of Life (AE-QoL) Questionnaire Score	The AE-QoL was developed to measure health-related quality of life (HRQoL) impairment in participants with recurrent angioedema. The AE-QoL is a self-administered questionnaire that can be completed in less than 5 minutes. It comprises 17 items across 4 domains: functioning, fatigue/mood, fears/shame, and food. Responses use a 5-point Likert scale ranging from 'never' to 'very often.' Global and domain scores range from 0 to 100, with higher scores indicating greater impairment	Up to Week 221