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

Study Overview
=================
Brief 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).

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.

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

Conditions
-----------------
Hereditary Angioedema

Intervention / Treatment
-----------------
* Drug: Donidalorsen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Satisfactory completion of ISIS 721744-CS2 (index study) through Week 17 with an acceptable safety and tolerability profile, per Sponsor and Investigator judgement Able and willing to participate in a 64-week study Females must be non-pregnant, non-lactating and either surgically sterile or post-menopausal 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 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donidalorsen<br>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<br>* Donidalorsen administered SC<br>* Other names: IONIS-PKK-LRx;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hereditary Angioedema, HAE