Study of AG10 in Amyloid Cardiomyopathy
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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 :
Completed
First Posted : March 8, 2018
Last Update Posted : November 20, 2019
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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 |
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 |
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 |
Actual Primary Completion Date : | October 5, 2018 |
Actual Study Completion Date : | October 5, 2018 |

Arm | Intervention/treatment |
---|---|
Active Comparator: AG10 Low Dose
Low dose group
|
Drug: AG10
TTR stabilizer |
Active Comparator: AG10 High Dose
High dose group
|
Drug: AG10
TTR stabilizer |
Placebo Comparator: Placebo |
Drug: Placebo Oral Tablet
Nonactive control |
- 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).

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Ages Eligible for Study: | 18 Years to 90 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
- Be a male or female ≥18 to ≤90 years of age.
- Have an established diagnosis of ATTR-CM with either wild-type transthyretin or a variant transthyretin genotype (assessed by genotyping, with patients with concurrent monoclonal gammopathy of undetermined significance requiring a confirmatory test using mass spectrometry) as defined by either positive endomyocardial biopsy or positive technetium pyrophosphate scan.
- Have a history of heart failure evidenced by at least one prior hospitalization for heart failure or clinical evidence of heart failure (without hospitalization) requiring medical management.
- Have NYHA Class II-III symptoms.
- Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use appropriate method(s) of contraception.
- For patients taking cardiovascular medical therapy, with the exception of diuretic dosing, must be on stable doses (defined as no greater than 50% dose adjustment and no categorical changes of medications) for at least 2 weeks prior to Screening.
Exclusion Criteria:
- Acute myocardial infarction, acute coronary syndrome or coronary revascularization within 90 days prior to Screening.
- Experienced stroke within 90 days prior to Screening.
- Has hemodynamic instability at Screening or Randomization that, in the judgment of the PI, would pose too great a risk for participation in the study.
- Has estimated glomerular filtration rate (GFR) <30 mL/min/1.73 m2 at Screening.
- Is likely to undergo heart transplantation within the next year.
- Has confirmed diagnosis of light-chain amyloidosis.
- Has abnormal liver function tests at Screening, defined as ALT or AST >3 × upper limit of normal (ULN) or total bilirubin >2 × ULN.
- Has abnormalities in clinical laboratory tests at Screening or Randomization that, in the judgment of the PI, would pose too great a risk for participation in the study.
- Known hypersensitivity to study drug (AG10 or placebo), its metabolites, or formulation excipient
- Current treatment with diflunisal, tafamidis, green tea, doxycycline, TUDCA/Ursodiol, Patisiran or Inotersen within 14 days or 5 half-lives of the prior investigational agent (whichever is longer) prior to Screening.
- Females who are pregnant or breastfeeding. Lactating females must agree to discontinue nursing before the study drug is administered. A negative serum pregnancy test at Screening and a negative urine pregnancy test at Randomization visit are required for female patients of childbearing potential.
- In the judgment of the investigator, has any clinically significant ongoing medical condition that might jeopardize the patient's safety or interfere with the study, including participation in another investigational drug or investigational device study within the 30 days prior to Screening with potential residual effects that might confound the results of this study.
- Has any laboratory abnormality or condition that, in the investigator's opinion, could adversely affect the safety of the patient or impair the assessment of study results.
- Has any condition that, in the opinion of the investigator, would preclude compliance with the study protocol such as a history of substance abuse, alcoholism or a psychiatric condition.
- Has participated in another investigational study within 14 days or 5 half-lives of the prior investigational agent (whichever is longer) prior to screening. Exceptions can be made in the case of observational and/or registry studies upon consultation with the Medical Monitor.
- Current treatment with, or chronic use of, a proton pump inhibitor (PPI) or histamine-receptor 2 (H2) antagonist within 14 days or 5 half-lives of the prior agent (whichever is longer) prior to Screening.

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 | |
Stanford University | |
Palo Alto, California, United States, 94304 | |
University of California San Francisco | |
San Francisco, California, United States, 94143 | |
United States, Connecticut | |
Yale University | |
New Haven, Connecticut, United States, 06520 | |
United States, Illinois | |
Northwestern University | |
Chicago, Illinois, United States, 60611 | |
United States, Massachusetts | |
Brigham and Women's Hospital | |
Boston, Massachusetts, United States, 02115 | |
Boston University | |
Boston, Massachusetts, United States, 02127 | |
United States, Minnesota | |
Mayo Clinic | |
Rochester, Minnesota, United States, 55905 | |
United States, New York | |
Columbia University | |
New York, New York, United States, 10032 | |
United States, Ohio | |
Cleveland Clinic | |
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 |
Responsible Party: | Eidos Therapeutics, a BridgeBio company |
ClinicalTrials.gov Identifier: | NCT03458130 |
Other Study ID Numbers: |
AG10-201 |
First Posted: | March 8, 2018 Key Record Dates |
Last Update Posted: | November 20, 2019 |
Last Verified: | June 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Cardiomyopathies Heart Diseases Cardiovascular Diseases |