Clinical trial NCT03536767: Open-Label Study of AG10 in Patients with Cardiomyopathy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Amyloid Cardiomyopathy
Lead sponsor: Eidos Therapeutics, a BridgeBio company
Sponsor class: INDUSTRY
First posted: 2018-05-25
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Assessment of long-term safety and tolerability: Incidence of each treatment-emergent adverse events
timeFrame: up to 60 Months or study completion by recommendation from safety monitoring committee
Secondary outcomes:
measure: AG10 Pharmacokinetics AUC
timeFrame: up to 60 Months or study completion by recommendation from safety monitoring committee
measure: AG10 Pharmacodynamic Assessments of TTR stabilization by Fluorescent Polarization Exclusion Assay
timeFrame: up to 60 Months or study completion by recommendation from safety monitoring committee
measure: AG10 Pharmacodynamic Assessments of TTR stabilization by Western Blot
timeFrame: up to 60 Months or study completion by recommendation from safety monitoring committee
measure: AG10 Pharmacodynamic Assessments: prealbumin
timeFrame: up to 60 Months or study completion by recommendation from safety monitoring committee
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Columbia University
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
References: