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

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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

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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

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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

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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

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

Additional relevant MeSH terms:

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Cardiomyopathies; Heart Diseases; Cardiovascular Diseases