Study of AG10 in Amyloid Cardiomyopathy
Condition: Familial ATTR-CM (ATTRm-CM, or FAC); Wild-type ATTR-CM (ATTRwt-CM)
MeSH terms: Cardiomyopathies
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): AG10; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): TTR stabilizer; Nonactive control
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A randomized, doubleblind, placebo-controlled, dose-ranging design is considered to be the most appropriate study design for meeting this objective. On the basis of information gained from previous clinical experience with AG10, the doses used in this study will be selected to determine the dose with the better safety and tolerability profile.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment