- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05392114
A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
Study Overview
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Ionis Pharmaceuticals
- Phone Number: (844) 910-0878
- Email: ionisHAE2study@clinicaltrialmedia.com
Study Locations
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Edegem, Belgium, 2650
- Active, not recruiting
- Ionis Investigative Site
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Sofia, Bulgaria, 1431
- Active, not recruiting
- Ionis Investigative Site
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Sofia, Bulgaria, 1680
- Active, not recruiting
- Ionis Investigative Site
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Edmonton, Canada, AB T6G 1Z1
- Active, not recruiting
- Ionis Investigative Site
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Ontario
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Ottawa, Ontario, Canada, K1H 1E4
- Active, not recruiting
- Ionis Investigative Site
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La Tronche, France, 38700
- Active, not recruiting
- Ionis Investigative Site
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Marseille, France, 13385
- Active, not recruiting
- Ionis Investigative Site
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Paris, France, 75012
- Active, not recruiting
- Ionis Investigative Site
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Berlin, Germany, 12203
- Active, not recruiting
- Ionis Investigative Site
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Frankfurt, Germany, 60590
- Active, not recruiting
- Ionis Investigative Site
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München, Germany, 81675
- Active, not recruiting
- Ionis Investigative Site
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Ashkelon, Israel, 7830604
- Active, not recruiting
- Ionis Investigative Site
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Haifa, Israel, 3104802
- Active, not recruiting
- Ionis Investigative Site
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Tel Aviv, Israel, 6423906
- Active, not recruiting
- Ionis Investigative Site
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Catania, Italy, 95123
- Active, not recruiting
- Ionis Investigative Site
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Milan, Italy, 20138
- Active, not recruiting
- Ionis Investigative Site
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Napoli, Italy, 80131
- Active, not recruiting
- Ionis Investigative Site
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Padova, Italy, 35128
- Active, not recruiting
- Ionis Investigative Site
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Palermo, Italy, 90146
- Active, not recruiting
- Ionis Investigative Site
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San Donato Milanese, Italy, 20097
- Active, not recruiting
- Ionis Investigative Site
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Amsterdam, Netherlands, 1105
- Active, not recruiting
- Ionis Investigative Site
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Groningen, Netherlands, 9713 AP
- Active, not recruiting
- Ionis Investigative Site
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Krakow, Poland, 31-501
- Active, not recruiting
- Ionis Investigative Site
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San Juan, Puerto Rico, PR 00927
- Recruiting
- Ionis Investigative Site
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Barcelona, Spain, 08035
- Active, not recruiting
- Ionis Investigative Site
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Barcelona, Spain, 08907
- Active, not recruiting
- Ionis Investigative Site
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Madrid, Spain, 28046
- Active, not recruiting
- Ionis Investigative Site
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Sevilla, Spain, 41013
- Active, not recruiting
- Ionis Investigative Site
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Valencia, Spain, 46026
- Active, not recruiting
- Ionis Investigative Site
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Altındağ, Turkey, 06230
- Active, not recruiting
- Ionis Investigative Site
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Bornova, Turkey, 35100
- Active, not recruiting
- Ionis Investigative Site
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Istanbul, Turkey, 34093
- Active, not recruiting
- Ionis Investigative Site
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Birmingham, United Kingdom, B9 5SS
- Active, not recruiting
- Ionis Investigative Site
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Bristol, United Kingdom, BS10 5NB
- Active, not recruiting
- Ionis Investigative Site
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London, United Kingdom, E1 2ES
- Active, not recruiting
- Ionis Investigative Site
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Arizona
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Paradise Valley, Arizona, United States, 85253
- Recruiting
- Ionis Investigative Site
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California
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La Jolla, California, United States, 92037
- Recruiting
- Ionis Investigative Site
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Santa Monica, California, United States, 90404
- Recruiting
- Ionis Investigative Site
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Walnut Creek, California, United States, 94598
- Recruiting
- Ionis Investigative Site
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Colorado
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Colorado Springs, Colorado, United States, 80907
- Recruiting
- Ionis Investigative Site
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Florida
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Tampa, Florida, United States, 33613
- Recruiting
- Ionis Investigative Site
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Kansas
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Kansas City, Kansas, United States, 66103
- Recruiting
- Ionis Investigative Site
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Recruiting
- Ionis Investigative Site
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Michigan
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Ann Arbor, Michigan, United States, 48109
- Recruiting
- Ionis Investigative Site
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Missouri
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Saint Louis, Missouri, United States, 63141
- Recruiting
- Ionis Investigative Site
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North Carolina
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Mooresville, North Carolina, United States, 28117
- Recruiting
- Ionis Investigative Site
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Ohio
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Cincinnati, Ohio, United States, 45236
- Recruiting
- Ionis Investigative Site
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Columbus, Ohio, United States, 43235
- Recruiting
- Ionis Investigative Site
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Pennsylvania
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Hershey, Pennsylvania, United States, 17033
- Recruiting
- Ionis Investigative Site
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Texas
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Dallas, Texas, United States, 75231
- Recruiting
- Ionis Investigative Site
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Utah
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Murray, Utah, United States, 84107
- Recruiting
- Ionis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: OLE Participants
Group 1 and Group 2 participants will be administered donidalorsen by SC injection for up to 157 weeks.
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Donidalorsen will be administered by SC injection.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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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
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Up to approximately 70 weeks, plus 104 weeks for Group 1; up to approximately 76 weeks, plus 104 weeks for Group 2
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time-normalized Number of Investigator-confirmed HAE Attacks (per Month)
Time Frame: Week 1 to Week 157 for Group 1 and Group 2
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Week 1 to Week 157 for Group 1 and Group 2
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Percentage of Investigator-confirmed HAE Attack-free Participants
Time Frame: Week 1 to Week 157 for Group 1 and Group 2
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Week 1 to Week 157 for Group 1 and Group 2
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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
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Week 1 to Week 157 for Group 1 and Group 2
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Number of Investigator-confirmed HAE Attacks Requiring Acute Therapy
Time Frame: Week 1 to Week 157 for Group 1 and Group 2
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Week 1 to Week 157 for Group 1 and Group 2
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Angioedema Quality of Life (AE-QoL) Questionnaire Total Score
Time Frame: Up to 157 weeks for Group 1 and Group 2
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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.
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Up to 157 weeks for Group 1 and Group 2
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Skin Diseases
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Hypersensitivity, Immediate
- Genetic Diseases, Inborn
- Skin Diseases, Vascular
- Hypersensitivity
- Urticaria
- Hereditary Complement Deficiency Diseases
- Primary Immunodeficiency Diseases
- Angioedema
- Angioedemas, Hereditary
Other Study ID Numbers
- ISIS 721744-CS7
- 2022-000757-93 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hereditary Angioedema
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Pharvaris Netherlands B.V.Active, not recruitingHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsUnited States, Poland, Germany, Austria, Bulgaria, Canada, Ireland, Italy, United Kingdom
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Pharvaris Netherlands B.V.CompletedHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsBulgaria, United States, Spain, Israel, Germany, Canada, Czechia, France, Hungary, Italy, Netherlands, Poland, United Kingdom
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Pharvaris Netherlands B.V.RecruitingHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsUnited States
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Pharvaris Netherlands B.V.RecruitingHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsUnited States, Bulgaria, Czechia, Hungary, Spain, France, Germany, Poland, Canada, Israel
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CENTOGENE GmbH RostockCompletedHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | C1 Esterase Inhibitor Deficiency | HAE | Angio Edema | C4 Deficiency | Hereditary Angioedema Type IIITurkey, Armenia, Georgia, India, Peru, Poland, Romania
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HAE Global Registry FoundationRecruitingHereditary Angioedema Type I and IIItaly
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KalVista Pharmaceuticals, Ltd.CompletedHereditary AngioedemaUnited States, Austria, Czechia, Germany, Hungary, Italy, Netherlands, North Macedonia, Poland, United Kingdom
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Prothya BiosolutionsCompletedHereditary Angioedema Type I | Angioneurotic EdemaNetherlands
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TakedaNot yet recruitingHereditary Angioedema (HAE)
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CSL BehringRecruitingHereditary Angioedema (HAE)United States, Israel
Clinical Trials on Donidalorsen
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Ionis Pharmaceuticals, Inc.CompletedHereditary AngioedemaUnited States, France, Netherlands, Spain, United Kingdom, Belgium, Bulgaria, Canada, Denmark, Germany, Israel, Italy, Poland, Turkey
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Ionis Pharmaceuticals, Inc.Active, not recruitingHereditary AngioedemaNetherlands, United States
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Ionis Pharmaceuticals, Inc.Completed
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Ionis Pharmaceuticals, Inc.CompletedHereditary AngioedemaUnited States, Netherlands