This prospective, randomized, multicenter, double-blind, parallel group, placebo-controlled, dose-ranging study will evaluate the safety, tolerability, PK (Pharmacokinetic) and PD (Pharmacodynamic) of AG10 compared to placebo administered on a background of stable heart failure therapy. Screening and randomization will be followed by a 28-day blinded, placebo-controlled treatment period.
A Phase 2, Randomized, Placebo-controlled, Dose-ranging Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AG10 in Patients with Symptomatic Transthyretin Amyloid Cardiomyopathy. The primary objective of this study is to evaluate the safety and tolerability of AG10 administered to adult patients with symptomatic transthyretin amyloid cardiomyopathy (ATTRCM). This study will be a Phase 2, randomized, placebo-controlled, dose-ranging study in 45 male and/or female patients with symptomatic ATTR-CM aged 18 through 90 years. If all doses are well tolerated, the duration of each patient's participation in the study will be 28 days of treatment. In addition, there will be a 28-day screening period before treatment and a 30-day follow-up period before the final Follow-up Visit. This prospective, randomized, multicenter, double-blind, parallel group, placebo-controlled, dose-ranging study will evaluate the safety, tolerability, PK and PD of AG10 compared to placebo administered on a background of stable heart failure therapy. Screening and randomization will be followed by a 28-day blinded, placebo-controlled treatment period. secondary objectives of this study are: to characterize the pharmacokinetics (PK) of AG10 administered orally twice daily in patients with symptomatic ATTRCM, and to describe the 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 Pharmacokinetic Pharmacodynamic (PKPD) relationship of AG10 in adult patients with symptomatic ATTRCM. Eligible patients will be randomized in a 1:1:1 ratio to placebo or one of two different doses of AG10 administered twice daily. A minimum of 30% of patients enrolled will be mutant ATTR-CM.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
49
TTR stabilizer
Nonactive control
Cedars-Sinai Medical Center
Beverly Hills, California, United States
Stanford University
Palo Alto, California, United States
University of California San Francisco
San Francisco, California, United States
Change in Diastolic Blood Pressure
Change in Diastolic Blood Pressure from Baseline to Day 28 (Postdose)
Time frame: Baseline to Day 28
Change in Heart Rate
Change in Heart Rate from Baseline to Day 28 (Postdose)
Time frame: Baseline to Day 28
Change in Respiratory Rate
Change in Respiratory Rate from Baseline to Day 28 (Postdose)
Time frame: Baseline to Day 28
Change in Temperature
Change in Temperature from Baseline to Day 28
Time frame: Baseline to Day 28
Change in Systolic Blood Pressure
Change in Systolic Blood Pressure from Baseline to Day 28
Time frame: Baseline to Day 28
Number of Participants With Threshold Levels of Overall % Stabilization >= 95% and >= 99% by Fluorescent Probe Exclusion (FPE)
In specialized lab tests on patient samples that measure the stability of the healthy form of TTR, both doses of AG10 were able to reach near complete stabilization.
Time frame: Day 1 to Day 28
Pharmacokinetic (PK): Steady State Trough Concentration of AG10
Non-fluctuating minimal amount of AG10 in blood at Day 14 and Day 28
Time frame: Day 14 and Day 28
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