An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)

• Sponsor: Ionis Pharmaceuticals, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05667493
• Collaborator: AstraZeneca (Industry)
• Enrollment: 1,400
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 80
• Patients Per Site Per Month: 17.5

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)	Drug: Eplontersen	Phase 3

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 1400 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Nov 30, 2022
• Anticipated Primary Completion Date: Apr 1, 2029
• Anticipated Study Completion Date: Aug 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eplontersen 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.	Drug: Eplontersen; Eplontersen will be administered by SC injection.; Other Names: ION-682884

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Baseline up to 36 months]

2. Change From Baseline in Platelet Count [Baseline up to 36 months]

3. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) [Baseline up to 36 months]

4. Change From Baseline in Urine Protein Creatinine Ratio (UPCR) [Baseline up to 36 months]

5. Change From Baseline in AST [Baseline up to 36 months]

6. Change From Baseline in ALT [Baseline up to 36 months]

7. Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters [Baseline up to 36 months]

8. Number of Participants With Clinically Significant Changes From Baseline in Thyroid-Stimulating Hormone (TSH) [Baseline up to 36 months]

9. Percentage of Participants With Anti-Drug Antibodies (ADA) [Baseline up to 36 months]

Secondary Outcome Measures

1. Change From Baseline in Transthyretin (TTR) Serum Levels [Baseline up to 36 months]

2. Change From Baseline in 6-minute Walk Test (6MWT) [Baseline up to 36 months]

3. Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) [Baseline up to 36 months]

4. Change From Baseline in Short Form Health Survey Questionnaire (SF-36) [Baseline up to 36 months]

5. Change From Baseline in 5 Level EuroQol - 5 Dimension (EQ-5D-5L) [Baseline up to 36 months]

6. Change From Baseline in Biomarker: N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP) [Baseline up to 36 months]

7. Change From Baseline in Biomarker: High Sensitivity Cardiac Troponin T (hs-cTnT) [Baseline up to 36 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 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.

2. Investigator is willing to treat the participant with open-label eplontersen.

3. Willingness to adhere to vitamin A supplementation per protocol.

Exclusion Criteria:

1. Permanently discontinued study drug administration while participating in the Index Study (ION 682884-CS2) or IST (ISIS 420915-CS101 Study).

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Health University Hospital	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Ionis Pharmaceuticals, Inc.
• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ionis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT05667493
• Other Study ID Numbers: ION-682884-CS12; 2022-000826-74
• First Posted: Dec 28, 2022
• Last Update Posted: Jan 17, 2023
• Last Verified: Jan 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• 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.: Amyloidosis
• Additional relevant MeSH terms: Cardiomyopathies; Amyloidosis

Study Results

No Results Posted as of Jan 17, 2023