Back to resultsAn Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
Primary Purpose
Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Eplontersen
Sponsored by
About this trial
This is an interventional treatment trial for Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM) focused on measuring Amyloidosis
Eligibility Criteria
Inclusion Criteria: Satisfactory completion of Treatment Period and the End of Treatment Visit of the Index Study (ION-682884-CS2) OR diagnosis of ATTR-CM and satisfactory participation on ISIS 420915- CS101 study as judged by the Investigator and Sponsor. Investigator is willing to treat the participant with open-label eplontersen. Willingness to adhere to vitamin A supplementation per protocol. Exclusion Criteria: Permanently discontinued study drug administration while participating in the Index Study (ION 682884-CS2) or IST (ISIS 420915-CS101 Study). Have any new condition or worsening of an existing condition that in the opinion of the Investigator or Sponsor would make the participant unsuitable for enrolment, or which could interfere with the participant participating in or completing the study, including the need for treatment with medications disallowed in the Index Study.
Sites / Locations
- Indiana University Health University HospitalRecruiting
- University of Maryland Medical CenterRecruiting
- Oregon Health and Science UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Eplontersen
Arm Description
Eplontersen will be administered once every month by sub-cutaneous (SC) injection for up to 36 months or 6 months after eplontersen is approved and available in the site's country, whichever occurs first.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Change From Baseline in Platelet Count
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
Change From Baseline in AST
Change From Baseline in ALT
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters
Number of Participants With Clinically Significant Changes From Baseline in Thyroid-Stimulating Hormone (TSH)
Percentage of Participants With Anti-Drug Antibodies (ADA)
Secondary Outcome Measures
Change From Baseline in Transthyretin (TTR) Serum Levels
Change From Baseline in 6-minute Walk Test (6MWT)
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)
Change From Baseline in Short Form Health Survey Questionnaire (SF-36)
Change From Baseline in 5 Level EuroQol - 5 Dimension (EQ-5D-5L)
Change From Baseline in Biomarker: N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)
Change From Baseline in Biomarker: High Sensitivity Cardiac Troponin T (hs-cTnT)
Full Information
NCT ID
NCT05667493
First Posted
July 12, 2022
Last Updated
May 23, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT05667493
Brief Title
An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
Official Title
An Open-Label Extension Study to Assess the Long-Term Safety of Eplontersen (ION-682884) in Patients With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2022 (Actual)
Primary Completion Date
April 2029 (Anticipated)
Study Completion Date
August 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of extended dosing with eplontersen in participants with ATTR-CM.
Detailed Description
This is a multicenter, open-label, Phase 3 study in up to approximately 1400 participants. Eligible participants will receive eplontersen once every 4 weeks for up to 36 months or 6 months after eplontersen is approved and available in the site's country, whichever occurs first. Participants will also receive daily supplemental doses of the recommended daily allowance (RDA) of vitamin A. This study will consist of the following periods: less than or equal to (≤) 10-week screening assessment period, up to 36-month treatment period, and up to 6-month post-treatment evaluation period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Keywords
Amyloidosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1400 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Eplontersen
Arm Type
Experimental
Arm Description
Eplontersen will be administered once every month by sub-cutaneous (SC) injection for up to 36 months or 6 months after eplontersen is approved and available in the site's country, whichever occurs first.
Intervention Type
Drug
Intervention Name(s)
Eplontersen
Other Intervention Name(s)
ION-682884
Intervention Description
Eplontersen will be administered by SC injection.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Time Frame
Baseline up to 36 months
Title
Change From Baseline in Platelet Count
Time Frame
Baseline up to 36 months
Title
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Time Frame
Baseline up to 36 months
Title
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
Time Frame
Baseline up to 36 months
Title
Change From Baseline in AST
Time Frame
Baseline up to 36 months
Title
Change From Baseline in ALT
Time Frame
Baseline up to 36 months
Title
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters
Time Frame
Baseline up to 36 months
Title
Number of Participants With Clinically Significant Changes From Baseline in Thyroid-Stimulating Hormone (TSH)
Time Frame
Baseline up to 36 months
Title
Percentage of Participants With Anti-Drug Antibodies (ADA)
Time Frame
Baseline up to 36 months
Secondary Outcome Measure Information:
Title
Change From Baseline in Transthyretin (TTR) Serum Levels
Time Frame
Baseline up to 36 months
Title
Change From Baseline in 6-minute Walk Test (6MWT)
Time Frame
Baseline up to 36 months
Title
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame
Baseline up to 36 months
Title
Change From Baseline in Short Form Health Survey Questionnaire (SF-36)
Time Frame
Baseline up to 36 months
Title
Change From Baseline in 5 Level EuroQol - 5 Dimension (EQ-5D-5L)
Time Frame
Baseline up to 36 months
Title
Change From Baseline in Biomarker: N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)
Time Frame
Baseline up to 36 months
Title
Change From Baseline in Biomarker: High Sensitivity Cardiac Troponin T (hs-cTnT)
Time Frame
Baseline up to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Satisfactory completion of Treatment Period and the End of Treatment Visit of the Index Study (ION-682884-CS2) OR diagnosis of ATTR-CM and satisfactory participation on ISIS 420915- CS101 study as judged by the Investigator and Sponsor.
Investigator is willing to treat the participant with open-label eplontersen.
Willingness to adhere to vitamin A supplementation per protocol.
Exclusion Criteria:
Permanently discontinued study drug administration while participating in the Index Study (ION 682884-CS2) or IST (ISIS 420915-CS101 Study).
Have any new condition or worsening of an existing condition that in the opinion of the Investigator or Sponsor would make the participant unsuitable for enrolment, or which could interfere with the participant participating in or completing the study, including the need for treatment with medications disallowed in the Index Study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ionis Pharmaceuticals
Phone
(844) 520-3239
Email
ionisATTRCM2study@clinicaltrialmedia.com
Facility Information:
Facility Name
Indiana University Health University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
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