A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
Primary Purpose
Hereditary Angioedema
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Donidalorsen
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Angioedema focused on measuring HAE
Eligibility Criteria
Inclusion Criteria
- Participants and, as applicable, legally authorized representatives (i.e., parent(s)/legal guardian), must provide written and signed informed consent form (ICF).
- Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1-INH concentrate or a bradykinin receptor (BK) 2-receptor antagonist) to treat angioedema attacks Open-Label Extension Participants ONLY
- Satisfactory completion of ISIS 721744-CS5 (randomized placebo-controlled index study) through Week 25 or participants who are allowed to exit ISIS 721744-CS5 study per protocol with an acceptable safety and tolerability profile New (not previously on donidalorsen) Participants ONLY
- Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent
- Participants must have a documented diagnosis of HAE-1/HAE-2
- Participants must be on a stable dose (≥ 12 weeks) of prophylaxis treatment with lanadelumab or berotralstat or SC C1-esterase inhibitor prior to the Screening Period Exclusion Criteria
Open-Label Extension Participants:
- Have any new condition or worsening of an existing condition or change or anticipated change in medication New (not previously on donidalorsen) Participants ONLY
- Concurrent diagnosis of any other type of recurrent angioedema, including acquired, idiopathic angioedema or HAE with normal C1-INH (also known as HAE Type III)
- Anticipated change in the use of concurrent androgen or tranexamic acid prophylaxis used to prevent angioedema attacks
- Any clinically-significant abnormalities in screening laboratory values
- Malignancy within 5 years of Screening, except for non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma that has been successfully treated.
- Hypersensitivity to the active substance (donidalorsen) or to any of the excipients
- Treatment with another investigational drug (non-oligonucleotide) or biological agent within 1 month of Screening or 5 half-lives of investigational agent, whichever is longer
- Recent history of, or current drug or alcohol abuse
- Participated in a prior donidalorsen study
Exposure to any of the following medications:
- Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption
- Oligonucleotides (including small interfering ribonucleic acid [siRNA]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received. This exclusion does not apply to vaccines
Sites / Locations
- Ionis Investigative SiteRecruiting
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
OLE Participants
Arm Description
Group 1 and Group 2 participants will be administered donidalorsen by SC injection for up to 157 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity
Secondary Outcome Measures
Time-normalized Number of Investigator-confirmed HAE Attacks (per Month)
Percentage of Investigator-confirmed HAE Attack-free Participants
Time-normalized Number of Moderate or Severe Investigator-confirmed HAE Attacks (per Month)
Number of Investigator-confirmed HAE Attacks Requiring Acute Therapy
Angioedema Quality of Life (AE-QoL) Questionnaire Total Score
The AE-QoL questionnaire is a validated tool to assess symptom-specific health-related QOL impairment in participants suffering from recurrent angioedema. The AE-QoL is a self-administered questionnaire comprising 17 questions across 4 domains: functioning, fatigue/mood, fears/shame, and food. The responses are scored from 1 to 5 where, 1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = very often. Total and domain scores range from 0 to 100, with higher scores indicating greater impairment.
Full Information
NCT ID
NCT05392114
First Posted
May 23, 2022
Last Updated
August 9, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05392114
Brief Title
A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
Official Title
An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 13, 2022 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
March 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the long-term safety and efficacy of donidalorsen in people with HAE and the effects of donidalorsen on the number of HAE attacks and their impact on quality of life (QoL).
Detailed Description
This is a Phase 3, multi-center, open-label, global study with donidalorsen in up to approximately 144 participants with HAE-1 (Type I) and HAE-2 (Type II). There are two groups in this study: 1) participants who roll over from another study of donidalorsen (open-label extension [OLE] participants), and 2) new participants who are not rolling over from another study of donidalorsen and were previously maintained on HAE prophylactic therapy with lanadelumab, berotralstat, or a C1-esterase inhibitor (C1-INH). The length of participation in the study is approximately 70 weeks for OLE participants and 76 weeks for other participants. Participants will receive donidalorsen in an Extended Treatment Period for up to an additional 104 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema
Keywords
HAE
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
144 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
OLE Participants
Arm Type
Experimental
Arm Description
Group 1 and Group 2 participants will be administered donidalorsen by SC injection for up to 157 weeks.
Intervention Type
Drug
Intervention Name(s)
Donidalorsen
Other Intervention Name(s)
ISIS 721744, IONIS-PKK-LRx
Intervention Description
Donidalorsen will be administered by SC injection.
Primary Outcome Measure Information:
Title
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity
Time Frame
Up to approximately 70 weeks, plus 104 weeks for Group 1; up to approximately 76 weeks, plus 104 weeks for Group 2
Secondary Outcome Measure Information:
Title
Time-normalized Number of Investigator-confirmed HAE Attacks (per Month)
Time Frame
Week 1 to Week 157 for Group 1 and Group 2
Title
Percentage of Investigator-confirmed HAE Attack-free Participants
Time Frame
Week 1 to Week 157 for Group 1 and Group 2
Title
Time-normalized Number of Moderate or Severe Investigator-confirmed HAE Attacks (per Month)
Time Frame
Week 1 to Week 157 for Group 1 and Group 2
Title
Number of Investigator-confirmed HAE Attacks Requiring Acute Therapy
Time Frame
Week 1 to Week 157 for Group 1 and Group 2
Title
Angioedema Quality of Life (AE-QoL) Questionnaire Total Score
Description
The AE-QoL questionnaire is a validated tool to assess symptom-specific health-related QOL impairment in participants suffering from recurrent angioedema. The AE-QoL is a self-administered questionnaire comprising 17 questions across 4 domains: functioning, fatigue/mood, fears/shame, and food. The responses are scored from 1 to 5 where, 1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = very often. Total and domain scores range from 0 to 100, with higher scores indicating greater impairment.
Time Frame
Up to 157 weeks for Group 1 and Group 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Participants and, as applicable, legally authorized representatives (i.e., parent(s)/legal guardian), must provide written and signed informed consent form (ICF).
Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1-INH concentrate or a bradykinin receptor (BK) 2-receptor antagonist) to treat angioedema attacks.
Open-Label Extension Participants ONLY:
Satisfactory completion of ISIS 721744-CS5 (randomized placebo-controlled index study) through Week 25 or participants who are allowed to exit ISIS 721744-CS5 study per protocol with an acceptable safety and tolerability profile.
New (not previously on donidalorsen) Participants ONLY:
Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent.
Participants must have a documented diagnosis of HAE-1/HAE-2.
Participants must be on a stable dose (≥ 12 weeks) of prophylaxis treatment with lanadelumab or berotralstat or SC C1-esterase inhibitor prior to the Screening Period.
Exclusion Criteria
Open-Label Extension Participants:
Have any new condition or worsening of an existing condition or change or anticipated change in medication.
New (not previously on donidalorsen) Participants ONLY:
Concurrent diagnosis of any other type of recurrent angioedema, including acquired, idiopathic angioedema or HAE with normal C1-INH (also known as HAE Type III).
Anticipated change in the use of concurrent androgen or tranexamic acid prophylaxis used to prevent angioedema attacks.
Any clinically-significant abnormalities in screening laboratory values.
Malignancy within 5 years of Screening, except for non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma that has been successfully treated.
Hypersensitivity to the active substance (donidalorsen) or to any of the excipients.
Treatment with another investigational drug (non-oligonucleotide) or biological agent within 1 month of Screening or 5 half-lives of investigational agent, whichever is longer.
Recent history of, or current drug or alcohol abuse.
Participated in a prior donidalorsen study.
Exposure to any of the following medications:
Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption.
Oligonucleotides (including small interfering ribonucleic acid [siRNA]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received. This exclusion does not apply to vaccines.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ionis Pharmaceuticals
Phone
(844) 910-0878
Email
ionisHAE2study@clinicaltrialmedia.com
Facility Information:
Facility Name
Ionis Investigative Site
City
Paradise Valley
State/Province
Arizona
ZIP/Postal Code
85253
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66103
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Mooresville
State/Province
North Carolina
ZIP/Postal Code
28117
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Sofia
ZIP/Postal Code
1680
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 1E4
Country
Canada
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Edmonton
ZIP/Postal Code
AB T6G 1Z1
Country
Canada
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Marseille
ZIP/Postal Code
13385
Country
France
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
München
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Ashkelon
ZIP/Postal Code
7830604
Country
Israel
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Haifa
ZIP/Postal Code
3104802
Country
Israel
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Catania
ZIP/Postal Code
95123
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Milan
ZIP/Postal Code
20138
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Padova
ZIP/Postal Code
35128
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
San Donato Milanese
ZIP/Postal Code
20097
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Amsterdam
ZIP/Postal Code
1105
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Groningen
ZIP/Postal Code
9713 AP
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
San Juan
ZIP/Postal Code
PR 00927
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Altındağ
ZIP/Postal Code
06230
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Bornova
ZIP/Postal Code
35100
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
Bristol
ZIP/Postal Code
BS10 5NB
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Ionis Investigative Site
City
London
ZIP/Postal Code
E1 2ES
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
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