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

Phase 1

• Conditions: Hereditary Angioedema; MedDRA version: 23.1Level: PTClassification code 10019860Term: Hereditary angioedemaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

• Registration Number: EUCTR2020-000197-14-NL
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-15
• Last Update Posted: 16 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

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 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety of extended dosing (52 weeks), and alternative dosing and/or dose frequency with ISIS 721744 in patients with HAE;Secondary Objective: To evaluate the efficacy of extended dosing (52 weeks), and alternative dosing and/or dose frequency with ISIS 721744 in patients with HAE;Primary end point(s): Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity ;Timepoint(s) of evaluation of this end point: adverse events will be collected at each visit

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -The time-normalized HAE attacks (monthly) by treatment<br> -Plasma PKK levels, plasma proenzyme activation and cHK levels<br>-Consumption of on-demand medications<br>-AE-QoL questionnaire score;Timepoint(s) of evaluation of this end point: -During the study patients will be instructed to report details of any HAE attack to the study site within 72 hours of the onset of the attack<br>-Plasma PKK levels, plasma proenzyme activation and cHK levels will be measured at Weeks 1, 5, 9, 13, 21, 29, 37, 45, 53, 65. <br>For patients switching to option 2 or 3, there will be additional timepoints<br>-During the study patients will be instructed to report details of any on-demand treatment to the study site within 72 hours of the onset of the attack<br>-AE-QOL questionnaire will be completed at Weeks 1, 13, 25, 37, 53 and 65