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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Drug: Donidalorsen

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Ionis Investigative Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Ionis Investigative Site
  • California
    • Santa Monica, California, United States, 90404
      • Ionis Investigative Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Ionis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Ionis Investigative Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Ionis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Ionis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donidalorsen; Participants will be administered donidalorsen SC for up to 53 weeks. Participants will also be administered donidalorsen in the extended treatment period for an additional 156 weeks, up to week 209.	Drug: Donidalorsen; Donidalorsen administered SC; Other Names: ISIS 721744; IONIS-PKK-LRx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity	Up to Week 221

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Time-normalized HAE Attacks (per Month) by Treatment		Up to Week 221
Plasma Prekallikrein (PKK) Levels		Up to Week 221
Consumption of On-demand Medications		Up to Week 221
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

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 11, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: HAE; Hereditary Angioedema
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: ISIS 721744-CS3; 2020-000197-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes