Open-Label Study of AG10 in Patients With Cardiomyopathy

• Sponsor: Eidos Therapeutics
• Information provided by (Responsible Party): Eidos Therapeutics

Study Description

Brief Summary:

This prospective, multicenter open-label study will evaluate the long-term safety, tolerability, PK and PD of AG10 administered on a background of stable heart failure therapy.

Condition or disease	Intervention/treatment	Phase
Amyloid Cardiomyopathy	Drug: AG10	Phase 2

Detailed Description:

An Open-Label Extension and Safety Monitoring Study of Patients with Symptomatic Transthyretin Cardiomyopathy Who Have Completed the Phase II Study AG10-201

The primary objective of this study is to evaluate the long-term safety and tolerability of AG10 administered to adult patients with symptomatic transthyretin amyloid cardiomyopathy (ATTR-CM) in patients who have completed the study AG10-201.

This study will be an Open-Label Extension and Safety Monitoring Study of up to 55 male and/or female patients with symptomatic ATTR-CM aged 18 through 90 years, who have completed the Phase II Study AG10-201. Enrollment into the study will be followed by visits at Day 14, Day 45, 3 Months and every 3 months thereafter. There will be one 7 to 14-day follow-up visit after last dose.

If all doses are well tolerated, the duration of each patient's participation in the study will continue based on periodic recommendations of the AG10 Data Monitoring Committee (DMC) and/or registration of the product for the treatment of symptomatic ATTR-CM.

The secondary objectives of this study are to characterize the pharmacokinetics (PK) of AG10 administered orally twice daily in patients with symptomatic ATTR-CM, and to describe the long-term pharmacodynamic (PD) properties of AG10 as assessed by established assays of transthyretin (TTR) stabilization, including Fluorescent Probe Exclusion (FPE) assay and Western blot, and to describe the PK-PD relationship of AG10 in adult patients with symptomatic ATTR-CM.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 55 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Extension and Safety Monitoring Study of Patients With Symptomatic Transthyretin Cardiomyopathy Who Have Completed the Phase II Study AG10-201
• Actual Study Start Date: August 8, 2018
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Open-Label	Drug: AG10; AG10 800mg twice daily, oral administration; Other Name: TTR Stabilizer

Outcome Measures

Primary Outcome Measures :

1. Assessment of long-term safety and tolerability: Incidence of each treatment-emergent adverse events [ Time Frame: up to 60 Months or study completion by recommendation from safety monitoring committee ]
   Incidence of each treatment-emergent adverse events

Secondary Outcome Measures :

1. AG10 Pharmacokinetics AUC [ Time Frame: up to 60 Months or study completion by recommendation from safety monitoring committee ]
   Area under the plasma concentration-time curve (AUC)
2. AG10 Pharmacodynamic Assessments of TTR stabilization by Fluorescent Polarization Exclusion Assay [ Time Frame: up to 60 Months or study completion by recommendation from safety monitoring committee ]
   AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Fluorescent Polarization Exclusion Assay (FPE)
3. AG10 Pharmacodynamic Assessments of TTR stabilization by Western Blot [ Time Frame: up to 60 Months or study completion by recommendation from safety monitoring committee ]
   AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot)
4. AG10 Pharmacodynamic Assessments: prealbumin [ Time Frame: up to 60 Months or study completion by recommendation from safety monitoring committee ]
   AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Completed participation in study AG10-201.
2. Willing and able to comply with the study medication regimen and all study requirements.
3. The ability to understand and provide informed consent, which must be obtained prior to initiation of study participation.
4. Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use effective method(s) of contraception.

Exclusion Criteria:

1. Hemodynamic instability that would pose too great a risk to the subject.
2. Abnormalities in clinical laboratory tests that would pose too great a risk to the subject.
3. Any clinically significant ongoing medical condition or any laboratory abnormality or condition that could adversely affect the safety of the patient.
4. Known hypersensitivity to study drug (AG10), its metabolites, or formulation excipients.
5. Likely to undergo heart transplantation or placement of a mechanical circulatory device within the next year.
6. Receiving current treatment with diflunisal, tafamidis, green tea, doxycycline, TUDCA/Ursodiol, patisiran, inotersen or any other investigational ATTR agent within 14 days or 5 half-lives of the prior investigational agent (whichever is longer) prior to dosing with study drug.
7. Females who are pregnant or breastfeeding. Lactating females must agree to discontinue nursing before the study drug is administered.

Contacts and Locations

Locations

United States, California

Stanford University

Palo Alto, California, United States, 94304

University of California San Francisco

San Francisco, California, United States, 94143

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06520

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, New York

Columbia University

New York, New York, United States, 10032

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29424

Sponsors and Collaborators

Eidos Therapeutics

More Information

• Responsible Party: Eidos Therapeutics
• ClinicalTrials.gov Identifier: NCT03536767 History of Changes
• Other Study ID Numbers: AG10-202
• First Posted: May 25, 2018
• Last Update Posted: April 16, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases