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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
Recruitment Status : Recruiting
First Posted : December 1, 2021
Last Update Posted : August 11, 2022
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

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

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.

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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


Arm Intervention/treatment
Experimental: Donidalorsen: Cohort A
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
Drug: Donidalorsen
Donidalorsen will be administered by SC injection.

Experimental: Donidalorsen: Cohort B
Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.
Drug: Donidalorsen
Donidalorsen will be administered by SC injection.

Placebo Comparator: Placebo: Cohort A
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
Drug: Placebo
Donidalorsen-matching placebo will be administered by SC injection.

Placebo Comparator: Placebo: Cohort B
Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.
Drug: Placebo
Donidalorsen-matching placebo will be administered by SC injection.




Primary Outcome Measures :
  1. 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 :
  1. Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25 [ Time Frame: Week 5 to Week 25 ]
  2. Percentage of Investigator-Confirmed HAE Attack-Free Participants From Week 5 to Week 25 [ Time Frame: Week 5 to Week 25 ]
  3. 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 ]
  4. 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 ]
  5. Number of Investigator-Confirmed HAE Attacks Requiring Acute HAE Therapy From Week 5 to Week 25 [ Time Frame: Week 5 to Week 25 ]
  6. 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.

  7. 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.



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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

  1. Participants, or their legally appointed and authorized representatives, must provide written and signed informed consent form (ICF)/assent
  2. Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent
  3. Participants must have a documented diagnosis of hereditary angioedema type 1 (HAE-1)/hereditary angioedema type 2 (HAE-2)
  4. Participants must:

    1. Experience a minimum of 2 HAE attacks (confirmed by the Investigator) during the Screening Period
    2. Be willing to complete the participant reported outcomes (PRO) assessments throughout the study
  5. Participants must have access to, and the ability to use acute medication(s) to treat angioedema attacks

Exclusion Criteria

  1. 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)
  2. Any clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the study
  3. Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of Screening
  4. Participated in a prior ISIS 721744 study
  5. Exposure to any of the following medications:

    1. Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption within 4 weeks prior to Screening
    2. Chronic prophylaxis with Takhzyro, Haegarda, Cinryze and Ruconest or Orladeyo within 5 half-lives prior to Screening
    3. 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
  6. 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
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Contact: Ionis Pharmaceuticals (844) 501-0233 IonisOasisStudy@clinicaltrialmedia.com

Locations
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United States, Arizona
Ionis Investigative Site Recruiting
Paradise Valley, Arizona, United States, 85253
United States, California
Ionis Investigative Site Recruiting
Santa Monica, California, United States, 90404
Ionis Investigative Site Recruiting
Vallejo, California, United States, 94589
United States, Colorado
Ionis Investigative Site Recruiting
Colorado Springs, Colorado, United States, 80907
United States, Florida
Ionis Investigative Site Recruiting
Tampa, Florida, United States, 33613
United States, Kansas
Ionis Investigative Site Recruiting
Kansas City, Kansas, United States, 66205
United States, Massachusetts
Ionis Investigative Site Recruiting
Boston, Massachusetts, United States, 02114
United States, Michigan
Ionis Investigative Site Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Ionis Investigative Site Recruiting
Saint Louis, Missouri, United States, 63141
United States, Ohio
Ionis Investigative Site Recruiting
Columbus, Ohio, United States, 43235
Ionis Investigative Site Recruiting
Toledo, Ohio, United States, 43617
United States, Texas
Ionis Investigative Site Recruiting
Dallas, Texas, United States, 75231
United States, Utah
Ionis Investigative Site Recruiting
Murray, Utah, United States, 84107
Belgium
Ionis Investigative Site Recruiting
Brussels, Belgium, 1020
Ionis Investigative Site Recruiting
Edegem, Belgium, 2650
Bulgaria
Ionis Investigative Site Recruiting
Sofia, Bulgaria, 1431
Ionis Investigative Site Recruiting
Sofia, Bulgaria, 1680
Canada, Ontario
Ionis Investigative Site Recruiting
Ottawa, Ontario, Canada, K1G6C6
France
Ionis Investigative Site Recruiting
La Tronche, France, 38700
Italy
Ionis Investigative Site Recruiting
Milan, Italy, 20138
Spain
Ionis Investigative Site Recruiting
Barcelona, Spain, 08035
Ionis Investigative Site Recruiting
Madrid, Spain, 28046
Ionis Investigative Site Recruiting
Sevilla, Spain, 41013
United Kingdom
Ionis Investigative Site Recruiting
Bristol, United Kingdom, BS10 5NB
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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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: August 11, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ionis Pharmaceuticals, Inc.:
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