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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| ClinicalTrials.gov Identifier: NCT05139810 |
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Recruitment Status :
Recruiting
First Posted : December 1, 2021
Last Update Posted : March 28, 2023
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Sponsor:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hereditary Angioedema | Drug: Donidalorsen Drug: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 84 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | December 3, 2021 |
| Estimated Primary Completion Date : | July 2023 |
| Estimated Study Completion Date : | October 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Hereditary angioedema
| Arm | Intervention/treatment |
|---|---|
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Experimental: Donidalorsen: Cohort A
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
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Drug: Donidalorsen
Donidalorsen will be administered by SC injection. |
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Experimental: Donidalorsen: Cohort B
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
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Drug: Donidalorsen
Donidalorsen will be administered by SC injection. |
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Placebo Comparator: Placebo: Cohort A
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
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Drug: Placebo
Donidalorsen-matching placebo will be administered by SC injection. |
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Placebo Comparator: Placebo: Cohort B
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
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Drug: Placebo
Donidalorsen-matching placebo will be administered by SC injection. |
Primary Outcome Measures :
- 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 Measures :
- Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25 [ Time Frame: Week 5 to Week 25 ]
- Percentage of Investigator-Confirmed HAE Attack-Free Participants From Week 5 to Week 25 [ Time Frame: Week 5 to Week 25 ]
- 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 ]
- 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 ]
- Number of Investigator-Confirmed HAE Attacks Requiring Acute HAE Therapy From Week 5 to Week 25 [ Time Frame: Week 5 to Week 25 ]
- Percentage of Participants who are Well Controlled on the Angioedema Control Test (AECT) at Week 25 [ Time Frame: 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 [ Time Frame: 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.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
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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
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05139810
Contacts
| Contact: Ionis Pharmaceuticals | (844) 501-0233 | IonisOasisStudy@clinicaltrialmedia.com |
Locations
Show 51 study locations
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
| Responsible Party: | Ionis Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT05139810 |
| Other Study ID Numbers: |
ISIS 721744-CS5 2021-002571-19 ( EudraCT Number ) |
| First Posted: | December 1, 2021 Key Record Dates |
| Last Update Posted: | March 28, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Ionis Pharmaceuticals, Inc.:
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HAE |
Additional relevant MeSH terms:
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Angioedema Angioedemas, Hereditary Vascular Diseases Cardiovascular Diseases Urticaria Skin Diseases, Vascular Skin Diseases |
Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Hereditary Complement Deficiency Diseases Primary Immunodeficiency Diseases Genetic Diseases, Inborn Immunologic Deficiency Syndromes |