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A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)

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ClinicalTrials.gov Identifier: NCT05392114
Recruitment Status : Recruiting
First Posted : May 26, 2022
Last Update Posted : September 16, 2022
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

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).

Condition or disease Intervention/treatment Phase
Hereditary Angioedema Drug: Donidalorsen Phase 3

Detailed Description:
This is a Phase 3, multi-center, open-label, global study with donidalorsen in up to approximately 114 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 subcutaneous (SC) C1-esterase inhibitor. The length of participation in the study is approximately 69 weeks for OLE participants and 75 weeks for other participants.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
Actual Study Start Date : July 13, 2022
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: OLE Participants
Participants will be administered donidalorsen by SC injection for up to 53 weeks.
Drug: Donidalorsen
Donidalorsen will be administered by SC injection.
Other Names:
  • ISIS 721744
  • IONIS-PKK-LRx




Primary Outcome Measures :
  1. Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity [ Time Frame: Up to approximately 70 weeks ]

Secondary Outcome Measures :
  1. Time-normalized Number of Investigator-confirmed HAE Attacks (per Month) From Week 1 to Week 53 [ Time Frame: Week 1 to Week 53 ]
  2. Time-normalized Number of Investigator-confirmed HAE Attacks (per Month) From Week 5 to Week 53 [ Time Frame: Week 5 to Week 53 ]
  3. Percentage of Investigator-confirmed HAE Attack-free Participants From Week 5 to Week 53 [ Time Frame: Week 5 to Week 53 ]
  4. Time-normalized Number of Moderate or Severe Investigator-confirmed HAE Attacks (per Month) From Week 5 to Week 53 [ Time Frame: Week 5 to Week 53 ]
  5. Number of Investigator-confirmed HAE Attacks Requiring Acute Therapy From Week 5 to Week 53 [ Time Frame: Week 5 to Week 53 ]
  6. Angioedema Quality of Life (AE-QoL) Questionnaire Total Score Over 53 weeks [ Time Frame: Up to 53 weeks ]
    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

  1. Participants and, as applicable, legally authorized representatives (i.e., parent(s)/legal guardian), must provide written and signed informed consent form (ICF).
  2. 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
  3. 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
  4. Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent
  5. Participants must have a documented diagnosis of HAE-1/HAE-2
  6. 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:

  1. Have any new condition or worsening of an existing condition or change or anticipated change in medication New (not previously on donidalorsen) Participants ONLY
  2. 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)
  3. Anticipated change in the use of concurrent androgen or tranexamic acid prophylaxis used to prevent angioedema attacks
  4. Any clinically-significant abnormalities in screening laboratory values
  5. 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.
  6. Hypersensitivity to the active substance (donidalorsen) or to any of the excipients
  7. 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
  8. Recent history of, or current drug or alcohol abuse
  9. Participated in a prior donidalorsen study
  10. Exposure to any of the following medications:

    1. Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption
    2. 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

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): NCT05392114


Contacts
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Contact: Ionis Pharmaceuticals (844) 910-0878 ionisHAE2study@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
Walnut Creek, California, United States, 94598
United States, Colorado
Ionis Investigative Site Recruiting
Colorado Springs, Colorado, United States, 80907
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
United States, Texas
Ionis Investigative Site Recruiting
Dallas, Texas, United States, 75231
United States, Utah
Ionis Investigative Site Recruiting
Murray, Utah, United States, 84107
Canada, Ontario
Ionis Investigative Site Recruiting
Ottawa, Ontario, Canada, K1H 1E4
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05392114    
Other Study ID Numbers: ISIS 721744-CS7
2022-000757-93 ( EudraCT Number )
First Posted: May 26, 2022    Key Record Dates
Last Update Posted: September 16, 2022
Last Verified: September 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