Back to resultsOASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
Primary Purpose
Hereditary Angioedema
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Donidalorsen
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Angioedema focused on measuring HAE
Eligibility Criteria
Inclusion Criteria
- Participants, or their legally appointed and authorized representatives, must provide written and signed informed consent form (ICF)/assent
- Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent
- Participants must have a documented diagnosis of hereditary angioedema type 1 (HAE-1)/hereditary angioedema type 2 (HAE-2)
Participants must:
- Experience a minimum of 2 HAE attacks (confirmed by the Investigator) during the Screening Period
- Be willing to complete the participant reported outcomes (PRO) assessments throughout the study
- Participants must have access to, and the ability to use acute medication(s) to treat angioedema attacks
Exclusion Criteria
- 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)
- Any clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the study
- Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of Screening
- Participated in a prior ISIS 721744 study
Exposure to any of the following medications:
- Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption within 4 weeks prior to Screening
- Chronic prophylaxis with Takhzyro, Haegarda, Cinryze and Ruconest or Orladeyo within 5 half-lives prior to Screening
- 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
- Recent history (3 years) of, or current drug or alcohol abuse
Sites / Locations
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
- Ionis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
Donidalorsen: Cohort A
Donidalorsen: Cohort B
Placebo: Cohort A
Placebo: Cohort B
Arm Description
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
Outcomes
Primary Outcome Measures
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 1 to Week 25
Secondary Outcome Measures
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25
Percentage of Investigator-Confirmed HAE Attack-Free Participants From Week 5 to Week 25
Time-Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25
Number of Participants With a Clinical Response Defined as a ≥ 50%, ≥ 70%, or ≥ 90% Reduction From Baseline (Screening Rate) in Investigator-confirmed HAE Attack Rate Between Week 5 to Week 25
Number of Investigator-Confirmed HAE Attacks Requiring Acute HAE Therapy From Week 5 to Week 25
Percentage of Participants who are Well Controlled on the Angioedema Control Test (AECT) at Week 25
The AECT is a validated participant-reported outcome instrument to assess disease activity in participants with recurrent angioedema. The questionnaire consists of four questions asking about the frequency and severity of angioedema experienced in the prior month. Each question has 5 response choices. The AECT can be used to identify participants with poorly controlled disease by working with a cutoff value of greater than or equal to 10 points. Participants who score less than 10 points (0-9) in the AECT have poorly controlled disease whereas participants with controlled disease score 10-16 points. Higher scores will indicate well controlled disease.
Change in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Week 25
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
NCT05139810
First Posted
November 18, 2021
Last Updated
June 22, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05139810
Brief Title
OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
Official Title
A Phase 3 Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ISIS 721744 in Patients With Hereditary Angioedema (HAE)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 3, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
April 2024 (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 safety and efficacy of donidalorsen in participants with HAE and effect of donidalorsen on the quality and pattern of HAE attacks and their impact on quality of life (QoL).
Detailed Description
This is a Phase 3, multi-center, double-blind, randomized, placebo-controlled study of donidalorsen in up to 84 participants. Participants will be randomized in a 2:1 ratio to Cohort A (donidalorsen or placebo every 4 weeks) or Cohort B (donidalorsen or placebo every 8 weeks), respectively. Within each Cohort, participants will be randomized in a 3:1 ratio to receive donidalorsen or matching-placebo. The length of participation in the study is approximately 11 months, which includes an up to 8-week Screening Period, a 25-week Treatment Period, and an up to 13-week Post-treatment Period.
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
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
91 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Donidalorsen: Cohort A
Arm Type
Experimental
Arm Description
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
Arm Title
Donidalorsen: Cohort B
Arm Type
Experimental
Arm Description
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
Arm Title
Placebo: Cohort A
Arm Type
Placebo Comparator
Arm Description
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
Arm Title
Placebo: Cohort B
Arm Type
Placebo Comparator
Arm Description
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
Intervention Type
Drug
Intervention Name(s)
Donidalorsen
Intervention Description
Donidalorsen will be administered by SC injection.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Donidalorsen-matching placebo will be administered by SC injection.
Primary Outcome Measure Information:
Title
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 1 to Week 25
Time Frame
Week 1 to Week 25
Secondary Outcome Measure Information:
Title
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25
Time Frame
Week 5 to Week 25
Title
Percentage of Investigator-Confirmed HAE Attack-Free Participants From Week 5 to Week 25
Time Frame
Week 5 to Week 25
Title
Time-Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25
Time Frame
Week 5 to Week 25
Title
Number of Participants With a Clinical Response Defined as a ≥ 50%, ≥ 70%, or ≥ 90% Reduction From Baseline (Screening Rate) in Investigator-confirmed HAE Attack Rate Between Week 5 to Week 25
Time Frame
Week 5 to Week 25
Title
Number of Investigator-Confirmed HAE Attacks Requiring Acute HAE Therapy From Week 5 to Week 25
Time Frame
Week 5 to Week 25
Title
Percentage of Participants who are Well Controlled on the Angioedema Control Test (AECT) at Week 25
Description
The AECT is a validated participant-reported outcome instrument to assess disease activity in participants with recurrent angioedema. The questionnaire consists of four questions asking about the frequency and severity of angioedema experienced in the prior month. Each question has 5 response choices. The AECT can be used to identify participants with poorly controlled disease by working with a cutoff value of greater than or equal to 10 points. Participants who score less than 10 points (0-9) in the AECT have poorly controlled disease whereas participants with controlled disease score 10-16 points. Higher scores will indicate well controlled disease.
Time Frame
Week 25
Title
Change in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Week 25
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
Week 25
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Participants, or their legally appointed and authorized representatives, must provide written and signed informed consent form (ICF)/assent
Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent
Participants must have a documented diagnosis of hereditary angioedema type 1 (HAE-1)/hereditary angioedema type 2 (HAE-2)
Participants must:
Experience a minimum of 2 HAE attacks (confirmed by the Investigator) during the Screening Period
Be willing to complete the participant reported outcomes (PRO) assessments throughout the study
Participants must have access to, and the ability to use acute medication(s) to treat angioedema attacks
Exclusion Criteria
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)
Any clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the study
Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of Screening
Participated in a prior ISIS 721744 study
Exposure to any of the following medications:
Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption within 4 weeks prior to Screening
Chronic prophylaxis with Takhzyro, Haegarda, Cinryze and Ruconest or Orladeyo within 5 half-lives prior to Screening
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
Recent history (3 years) of, or current drug or alcohol abuse
Facility Information:
Facility Name
Ionis Investigative Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Ionis Investigative Site
City
San Diego
State/Province
California
ZIP/Postal Code
92122
Country
United States
Facility Name
Ionis Investigative Site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Ionis Investigative Site
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Ionis Investigative Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Ionis Investigative Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Ionis Investigative Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Ionis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Ionis Investigative Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Ionis Investigative Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Ionis Investigative Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
Ionis Investigative Site
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43617
Country
United States
Facility Name
Ionis Investigative Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Ionis Investigative Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Ionis Investigative Site
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
Ionis Investigative Site
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Ionis Investigative Site
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Ionis Investigative Site
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Ionis Investigative Site
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Ionis Investigative Site
City
Sofia
ZIP/Postal Code
1680
Country
Bulgaria
Facility Name
Ionis Investigative Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1G6C6
Country
Canada
Facility Name
Ionis Investigative Site
City
Edmonton
ZIP/Postal Code
T6G 2G3
Country
Canada
Facility Name
Ionis Investigative Site
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Ionis Investigative Site
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
Ionis Investigative Site
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Ionis Investigative Site
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Ionis Investigative Site
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Ionis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Ionis Investigative Site
City
Munich
ZIP/Postal Code
81675
Country
Germany
Facility Name
Ionis Investigative Site
City
Ashkelon
ZIP/Postal Code
78278
Country
Israel
Facility Name
Ionis Investigative Site
City
Haifa
ZIP/Postal Code
3104802
Country
Israel
Facility Name
Ionis Investigative Site
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Ionis Investigative Site
City
Catania
ZIP/Postal Code
95124
Country
Italy
Facility Name
Ionis Investigative Site
City
Milan
ZIP/Postal Code
20138
Country
Italy
Facility Name
Ionis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Ionis Investigative Site
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Ionis Investigative Site
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Facility Name
Ionis Investigative Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Ionis Investigative Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Ionis Investigative Site
City
Kraków
ZIP/Postal Code
31-503
Country
Poland
Facility Name
Ionis Investigative Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Ionis Investigative Site
City
Barcelona
ZIP/Postal Code
8907
Country
Spain
Facility Name
Ionis Investigative Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Ionis Investigative Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Ionis Investigative Site
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Ionis Investigative Site
City
Ankara
ZIP/Postal Code
6230
Country
Turkey
Facility Name
Ionis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Ionis Investigative Site
City
İzmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Ionis Investigative Site
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Ionis Investigative Site
City
Bristol
ZIP/Postal Code
BS10 5NB
Country
United Kingdom
Facility Name
Ionis Investigative Site
City
London
ZIP/Postal Code
E1 1FR
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
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