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 was 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).

This was an open-label extension study of donidalorsen in 20 participants with HAE. The length of participation in the study was approximately 68 weeks, which included 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 received donidalorsen in an extended treatment period for up to an additional 156 weeks. Participants taking part in the extended treatment period entered the 12-week post-treatment period after completion of, or early termination from, the extended treatment period.

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