OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)

December 29, 2023 updated by: Ionis Pharmaceuticals, Inc.

A Phase 3 Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ISIS 721744 in Patients With Hereditary Angioedema (HAE)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

91

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Brussels, Belgium, 1020
        • Ionis Investigative Site
      • Brussels, Belgium, 1200
        • Ionis Investigative Site
      • Edegem, Belgium, 2650
        • Ionis Investigative Site
  • Bulgaria
      • Sofia, Bulgaria, 1431
        • Ionis Investigative Site
      • Sofia, Bulgaria, 1680
        • Ionis Investigative Site
  • Canada
      • Edmonton, Canada, T6G 2G3
        • Ionis Investigative Site
    • Ontario
      • Ottawa, Ontario, Canada, K1G6C6
        • Ionis Investigative Site
  • Denmark
      • Odense, Denmark, 5000
        • Ionis Investigative Site
  • France
      • La Tronche, France, 38700
        • Ionis Investigative Site
      • Marseille, France, 13385
        • Ionis Investigative Site
      • Paris, France, 75012
        • Ionis Investigative Site
  • Germany
      • Berlin, Germany, 12203
        • Ionis Investigative Site
      • Frankfurt, Germany, 60590
        • Ionis Investigative Site
      • Munich, Germany, 81675
        • Ionis Investigative Site
  • Israel
      • Ashkelon, Israel, 78278
        • Ionis Investigative Site
      • Haifa, Israel, 3104802
        • Ionis Investigative Site
      • Tel Aviv, Israel, 6423906
        • Ionis Investigative Site
  • Italy
      • Catania, Italy, 95124
        • Ionis Investigative Site
      • Milan, Italy, 20138
        • Ionis Investigative Site
      • Napoli, Italy, 80131
        • Ionis Investigative Site
      • Padova, Italy, 35128
        • Ionis Investigative Site
      • Palermo, Italy, 90146
        • Ionis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Ionis Investigative Site
      • Groningen, Netherlands, 9713 GZ
        • Ionis Investigative Site
  • Poland
      • Kraków, Poland, 31-503
        • Ionis Investigative Site
  • Spain
      • Barcelona, Spain, 08035
        • Ionis Investigative Site
      • Barcelona, Spain, 8907
        • Ionis Investigative Site
      • Madrid, Spain, 28046
        • Ionis Investigative Site
      • Sevilla, Spain, 41013
        • Ionis Investigative Site
      • Valencia, Spain, 46026
        • Ionis Investigative Site
  • Turkey
      • Ankara, Turkey, 6230
        • Ionis Investigative Site
      • Istanbul, Turkey, 34093
        • Ionis Investigative Site
      • İzmir, Turkey, 35100
        • Ionis Investigative Site
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
        • Ionis Investigative Site
      • Bristol, United Kingdom, BS10 5NB
        • Ionis Investigative Site
      • London, United Kingdom, E1 1FR
        • Ionis Investigative Site
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85251
        • Ionis Investigative Site
    • California
      • San Diego, California, United States, 92122
        • Ionis Investigative Site
      • Santa Monica, California, United States, 90404
        • Ionis Investigative Site
      • Walnut Creek, California, United States, 94598
        • Ionis Investigative Site
    • Colorado
      • Colorado Springs, Colorado, United States, 80907
        • Ionis Investigative Site
    • Florida
      • Tampa, Florida, United States, 33613
        • Ionis Investigative Site
    • Kansas
      • Kansas City, Kansas, United States, 66205
        • Ionis Investigative Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Ionis Investigative Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Ionis Investigative Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Ionis Investigative Site
    • Ohio
      • Columbus, Ohio, United States, 43235
        • Ionis Investigative Site
      • Toledo, Ohio, United States, 43617
        • Ionis Investigative Site
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Ionis Investigative Site
    • Texas
      • Dallas, Texas, United States, 75231
        • Ionis Investigative Site
    • Utah
      • Murray, Utah, United States, 84107
        • Ionis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 1 to Week 25
Time Frame: Week 1 to Week 25
Week 1 to Week 25

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) From Week 5 to Week 25
Time Frame: Week 5 to Week 25
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
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
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
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
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.
Week 25
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.
Week 25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ionis Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 3, 2021

Primary Completion (Actual)

November 6, 2023

Study Completion (Actual)

November 9, 2023

Study Registration Dates

First Submitted

November 18, 2021

First Submitted That Met QC Criteria

November 18, 2021

First Posted (Actual)

December 1, 2021

Study Record Updates

Last Update Posted (Estimated)

January 3, 2024

Last Update Submitted That Met QC Criteria

December 29, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISIS 721744-CS5
  • 2021-002571-19 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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.

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