Open-Label Study of AG10 in Patients With Cardiomyopathy

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Amyloid Cardiomyopathy
• Intervention / Treatment: Drug: AG10

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 until Month 54. After the Month 54 Visit, study visits will be every 6 months. There will be one follow-up visit approximately 30 days 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 Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29424
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Open-Label	Drug: AG10; AG10 800mg twice daily, oral administration; Other Names: TTR Stabilizer

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Eidos Therapeutics, a BridgeBio company

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 8, 2018
• Primary Completion (ANTICIPATED): July 1, 2027
• Study Completion (ANTICIPATED): July 1, 2027

Study Registration Dates

• First Submitted: May 11, 2018
• First Submitted That Met QC Criteria: May 23, 2018
• First Posted (ACTUAL): May 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 3, 2023
• Last Update Submitted That Met QC Criteria: February 1, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiomyopathies
• Other Study ID Numbers: AG10-202

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