Study of AG10 in Amyloid Cardiomyopathy

NCT03458130 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AG10-201
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Familial ATTR-CM (ATTRm-CM, or FAC); Wild-type ATTR-CM (ATTRwt-CM)

Outcome Measures

Primary Outcomes (5)

• Change in Diastolic Blood Pressure

  Change in Diastolic Blood Pressure from Baseline to Day 28 (Postdose)

  Baseline to Day 28

• Change in Heart Rate

  Change in Heart Rate from Baseline to Day 28 (Postdose)

  Baseline to Day 28

• Change in Respiratory Rate

  Change in Respiratory Rate from Baseline to Day 28 (Postdose)

  Baseline to Day 28

• Change in Temperature

  Change in Temperature from Baseline to Day 28

  Baseline to Day 28

• Change in Systolic Blood Pressure

  Change in Systolic Blood Pressure from Baseline to Day 28

  Baseline to Day 28

Secondary Outcomes (2)

• Number of Participants With Threshold Levels of Overall % Stabilization >= 95% and >= 99% by Fluorescent Probe Exclusion (FPE)

  Day 1 to Day 28

• Pharmacokinetic (PK): Steady State Trough Concentration of AG10

  Day 14 and Day 28

Study Arms (3)

AG10 Low Dose

ACTIVE COMPARATOR

AG10 400mg tablets twice daily for 28 days

Drug: AG10

AG10 High Dose

ACTIVE COMPARATOR

AG10 800mg tablets twice daily for 28 days

Drug: AG10

Placebo

PLACEBO COMPARATOR

Placebo tablets twice daily for 28 days

Drug: Placebo Oral Tablet

Interventions

AG10 DRUG

TTR stabilizer

AG10 High Dose; AG10 Low Dose

Placebo Oral Tablet DRUG

Nonactive control

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 New York Heart Association (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.

You may not qualify if:

• 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 Principal Investigator (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 Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (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, tauroursodeoxycholic acid (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.

Sponsors & Collaborators

• Eidos Therapeutics, a BridgeBio company: lead

Study Sites (13)

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston University

Boston, Massachusetts, 02127, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29424, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• Judge DP, Heitner SB, Falk RH, Maurer MS, Shah SJ, Witteles RM, Grogan M, Selby VN, Jacoby D, Hanna M, Nativi-Nicolau J, Patel J, Rao S, Sinha U, Turtle CW, Fox JC. Transthyretin Stabilization by AG10 in Symptomatic Transthyretin Amyloid Cardiomyopathy. J Am Coll Cardiol. 2019 Jul 23;74(3):285-295. doi: 10.1016/j.jacc.2019.03.012. Epub 2019 Mar 15.

  PMID: 30885685 DERIVED

Results Point of Contact

• Title: Mark McGovern, Vice President of Clinical Operations
• Organization: Eidos Therapeutics

medinfo@eidostx.com

415-887-1471

Study Officials

• MARK MCGOVERN, RN

  Eidos Therapeutics, a BridgeBio company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 7, 2018
• First Posted: March 8, 2018
• Study Start: April 27, 2018
• Primary Completion: October 5, 2018
• Study Completion: October 5, 2018
• Last Updated: November 16, 2022
• Results First Posted: November 16, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)