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

• ClinicalTrials.gov Identifier: NCT04307381
• Recruitment Status: Active, not recruiting
• First Posted: March 13, 2020
• Last Update Posted: February 7, 2024
• Sponsor: Ionis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Ionis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: March 11, 2020
• First Posted Date: March 13, 2020
• Last Update Posted Date: February 7, 2024
• Actual Study Start Date: April 1, 2020
• Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 19, 2023): Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity [ Time Frame: Up to Week 221 ]
• Original Primary Outcome Measures (submitted: March 11, 2020): Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity [ Time Frame: Up to Week 65 ]

Current Secondary Outcome Measures (submitted: March 19, 2023)

• The Time-normalized HAE Attacks (per Month) by Treatment [ Time Frame: Up to Week 221 ]
• Plasma Prekallikrein (PKK) Levels [ Time Frame: Up to Week 221 ]
• Consumption of On-demand Medications [ Time Frame: Up to Week 221 ]
• Angioedema Quality of Life (AE-QoL) Questionnaire Score [ Time Frame: Up to Week 221 ]
  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

Original Secondary Outcome Measures (submitted: March 11, 2020)

• The Time-normalized HAE Attacks (per Month) by Treatment [ Time Frame: Up to Week 65 ]
• Plasma Prekallikrein (PKK) Levels [ Time Frame: Up to Week 65 ]
• Plasma Proenzyme Activation [ Time Frame: Up to Week 65 ]
• Plasma Cleaved High Molecular Weight Kininogen (cHK) Level [ Time Frame: Up to Week 65 ]
• Consumption of On-demand Medications [ Time Frame: Up to Week 65 ]
• Angioedema Quality of Life (AE-QoL) Questionnaire Score [ Time Frame: Up to Week 65 ]
  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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hereditary Angioedema

Intervention

Drug: Donidalorsen

Donidalorsen administered SC

Other Names:

• ISIS 721744
• IONIS-PKK-LRx

Study Arms

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.

Intervention: Drug: Donidalorsen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 9, 2021): 20
• Original Estimated Enrollment (submitted: March 11, 2020): 24
• Estimated Study Completion Date: April 2025
• Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands, United States

Administrative Information

• NCT Number: NCT04307381
• Other Study ID Numbers: ISIS 721744-CS3; 2020-000197-14 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ionis Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ionis Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ionis Pharmaceuticals, Inc.
• Verification Date: February 2024