Clinical trial NCT04307381: An Extension Study of Donidalorsen (IONIS-PKK-LRx) in Participants With Hereditary Angioedema
Official title: An Open-Label Extension Study of ISIS 721744 in Patients With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hereditary Angioedema
Keywords: Hereditary Angioedema
HAE
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity
timeFrame: Up to Week 221
Secondary outcomes:
measure: The Time-normalized HAE Attacks (per Month) by Treatment
timeFrame: Up to Week 221
measure: Plasma Prekallikrein (PKK) Levels
timeFrame: Up to Week 221
measure: Consumption of On-demand Medications
timeFrame: Up to Week 221
measure: Angioedema Quality of Life (AE-QoL) Questionnaire Score
timeFrame: Up to Week 221
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Ionis Investigative Site
state: Arizona
city: Santa Monica
country: United States
facility: Ionis Investigative Site
state: California
city: Plymouth
country: United States
facility: Ionis Investigative Site
state: Minnesota
city: Cincinnati
country: United States
facility: Ionis Investigative Site
state: Ohio
city: Hershey
country: United States
facility: Ionis Investigative Site
state: Pennsylvania
city: Dallas
country: United States
facility: Ionis Investigative Site
state: Texas
city: Amsterdam
country: Netherlands
facility: Ionis Investigative Site
Study officials:
References: