Open-Label Study of AG10 in Patients With Cardiomyopathy

Amyloid Cardiomyopathy Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03536767
• Other study ID #: AG10-202
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 8, 2018
• Est. completion date: July 2027

Study information

• Verified date: February 2023
• Source: Eidos Therapeutics, a BridgeBio company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 55
• Est. completion date: July 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyloid Cardiomyopathy
• Cardiomyopathies

Intervention

Drug:
• AG10
AG10 800mg twice daily, oral administration

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Yale University	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Stanford University	Palo Alto	California
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Eidos Therapeutics, a BridgeBio company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	AG10 Pharmacokinetics AUC	Area under the plasma concentration-time curve (AUC)	up to 60 Months or study completion by recommendation from safety monitoring committee
Secondary	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
Secondary	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
Secondary	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