Study of AG10 in Amyloid Cardiomyopathy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03458130|
Recruitment Status : Active, not recruiting
First Posted : March 8, 2018
Last Update Posted : June 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Familial ATTR-CM (ATTRm-CM, or FAC) and Wild-type ATTR-CM (ATTRwt-CM)||Drug: AG10 Drug: Placebo Oral Tablet||Phase 2|
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 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 (Clinical Trial)|
|Actual Enrollment :||49 participants|
|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)|
|Official Title:||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|
|Actual Study Start Date :||April 27, 2018|
|Estimated Primary Completion Date :||September 28, 2018|
|Estimated Study Completion Date :||September 28, 2018|
Active Comparator: AG10 Low Dose
Low dose group
Active Comparator: AG10 High Dose
High dose group
|Placebo Comparator: Placebo||
Drug: Placebo Oral Tablet
- Assessment of safety and tolerability [ Time Frame: 28 Days ]Incidence of each treatment-emergent adverse events
- AG10 Pharmacokinetics AUC [ Time Frame: 28 Days ]Area under the plasma concentration-time curve (AUC)
- AG10 Pharmacodynamic Assessments of TTR stabilization by Fluorescent Polarization Exclusion Assay [ Time Frame: 28 Days ]AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Fluorescent Polarization Exclusion Assay (FPE)
- AG10 Pharmacodynamic Assessments of TTR stabilization by Western Blot [ Time Frame: 28 Days ]AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot)
- AG10 Pharmacodynamic Assessments: prealbumin [ Time Frame: 28 Days ]AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03458130
|United States, California|
|Cedars-Sinai Medical Center|
|Beverly Hills, California, United States, 90211|
|Palo Alto, California, United States, 94304|
|University of California San Francisco|
|San Francisco, California, United States, 94143|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06520|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Boston, Massachusetts, United States, 02127|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|New York, New York, United States, 10032|
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|United States, South Carolina|
|Medical University of South Carolina|
|Charleston, South Carolina, United States, 29424|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84132|