Familial ATTR-CM (ATTRm-CM, or FAC)Phase 2NCT03458130

Study of AG10 in Amyloid Cardiomyopathy

A Phase 2 study testing AG10 in people with Familial ATTR-CM (ATTRm-CM, or FAC) and Wild-type ATTR-CM (ATTRwt-CM), run by Eidos Therapeutics, a BridgeBio company at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 90 years
Conditions the study is for: Familial ATTR-CM (ATTRm-CM, or FAC), Wild-type ATTR-CM (ATTRwt-CM)
What is being tested?: AG10
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 49 participants
Where: 13 sitesUnited States
Study dates: 27 Apr 2018to 5 Oct 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.
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.

Trial locations and contacts

13 sites in 1 country.

City, postcode or hospital

13 sites in 1 country

United States13 sites

Cedars-Sinai Medical Center
Beverly Hills, California, 90211
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Boston University
Boston, Massachusetts, 02127
Medical University of South Carolina
Charleston, South Carolina, 29424
Northwestern University
Chicago, Illinois, 60611
Cleveland Clinic
Cleveland, Ohio, 44195
Yale University
New Haven, Connecticut, 06520
Columbia University
New York, New York, 10032
Stanford University
Palo Alto, California, 94304
Oregon Health & Science University
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84132
University of California San Francisco
San Francisco, California, 94143

Other trials in United States

About this study

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

Read the 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.

Conditions: Familial ATTR-CM (ATTRm-CM, or FAC), Wild-type ATTR-CM (ATTRwt-CM)
Being tested: AG10, Placebo Oral Tablet

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AG10Drug
TTR stabilizer
Placebo Oral TabletDrug
Nonactive control

Study groups in NCT03458130
Study group	Role	What they receive
AG10 Low Dose	Active comparator	AG10 400mg tablets twice daily for 28 days Receives: Drug: AG10
AG10 High Dose	Active comparator	AG10 800mg tablets twice daily for 28 days Receives: Drug: AG10
Placebo	Placebo comparator	Placebo tablets twice daily for 28 days Receives: Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Diastolic Blood Pressure
Change in Diastolic Blood Pressure from Baseline to Day 28 (Postdose)
Measured: Baseline to Day 28
Change in Heart Rate
Change in Heart Rate from Baseline to Day 28 (Postdose)
Measured: Baseline to Day 28
Change in Respiratory Rate
Change in Respiratory Rate from Baseline to Day 28 (Postdose)
Measured: Baseline to Day 28
Change in Temperature
Change in Temperature from Baseline to Day 28
Measured: Baseline to Day 28
Change in Systolic Blood Pressure
Change in Systolic Blood Pressure from Baseline to Day 28
Measured: Baseline to Day 28

Secondary outcomes (2)

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.
Measured: 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
Measured: Day 14 and Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Apr 20185 Oct 2018

First posted8 Mar 2018
Study start27 Apr 2018
Primary completion5 Oct 2018
Study completion5 Oct 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Familial ATTR-CM (ATTRm-CM, or FAC)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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 blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 49 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03458130
Sponsor's protocol ID: AG10-201
Status last verified: Oct 2022
First submitted: 7 Feb 2018
Last updated: 16 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Testani JM, Judge DP, Borlaug BA, Cherney D, Cox ZL, Gillmore JD, Lewis JB, Adler SH, Cao X, Castano A, Fox JC, Katz L, Mathur V, Xiong K, Butler J, Masri A. Effects of Acoramidis on Kidney Function in Transthyretin Amyloid Cardiomyopathy. Circ Heart Fail. 2026 Jul 2:e014656. doi: 10.1161/CIRCHEARTFAILURE.126.014656. Online ahead of print.
PubMed 42389794
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.
PubMed 30885685

Study at a glance

From the registry record, last updated by the sponsor on 16 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03458130
Acronym / sponsor ID: AG10-201
Conditions: Familial ATTR-CM (ATTRm-CM, or FAC), Wild-type ATTR-CM (ATTRwt-CM)
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 49 participants (actual)
Lead sponsor: Eidos Therapeutics, a BridgeBio companyIndustry (pharma, biotech, devices)
Study start: 27 Apr 2018 (actual)
Primary completion: 5 Oct 2018 (actual)
Study completion: 5 Oct 2018 (actual)
First posted: 8 Mar 2018 (actual)
Results: Posted 16 Nov 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3
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.

Arm	Type	Receives
AG10 Low Dose	Active comparator	Drug: AG10AG10 400mg tablets twice daily for 28 days
AG10 High Dose	Active comparator	Drug: AG10AG10 800mg tablets twice daily for 28 days
Placebo	Placebo comparator	Drug: Placebo Oral TabletPlacebo tablets twice daily for 28 days

Who may qualify

Ages: 18 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (16 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AG10TTR stabilizer	Drug	AG10 High Dose, AG10 Low Dose
Placebo Oral TabletNonactive control	Drug	Placebo

Primary outcome

Change in Diastolic Blood Pressure
Time frame: Baseline to Day 28
Change in Diastolic Blood Pressure from Baseline to Day 28 (Postdose)
Change in Heart Rate
Time frame: Baseline to Day 28
Change in Heart Rate from Baseline to Day 28 (Postdose)
Change in Respiratory Rate
Time frame: Baseline to Day 28
Change in Respiratory Rate from Baseline to Day 28 (Postdose)
Change in Temperature
Time frame: Baseline to Day 28
Change in Temperature from Baseline to Day 28
Change in Systolic Blood Pressure
Time frame: Baseline to Day 28
Change in Systolic Blood Pressure from Baseline to Day 28

2 secondary outcomes

Number of Participants With Threshold Levels of Overall % Stabilization >= 95% and >= 99% by Fluorescent Probe Exclusion (FPE)
Time frame: Day 1 to Day 28
Pharmacokinetic (PK): Steady State Trough Concentration of AG10
Time frame: Day 14 and Day 28

Results and safety

Results posted to the registry on 16 Nov 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AG10 400mg	16	16
AG10 800mg	16	16
Placebo	17	17

Primary outcome: Change in Diastolic Blood Pressure

Time frame: Baseline to Day 28. Mean (Standard Deviation). Unit: mm Hg

Measure	AG10 400mg n = 16	AG10 800mg n = 16	Placebo n = 17
Change in Diastolic Blood Pressure from Baseline to Day 28 (Predose)	-3.1 (10.06)	-3.3 (11.19)	-4.3 (7.78)
Change in Diastolic Blood Pressure from Baseline to Day 28 (Postdose)	-2.6 (9.66)	0.3 (8.54)	-4.9 (9.17)

Primary outcome: Change in Heart Rate

Time frame: Baseline to Day 28. Mean (Standard Deviation). Unit: beats/minute

Measure	AG10 400mg n = 16	AG10 800mg n = 16	Placebo n = 17
Change in heart rate from Baseline to Day 28 (Predose)	-2.7 (6.88)	-3.8 (6.55)	-0.4 (6.34)
Change in heart rate from Baseline to Day 28 (Postdose)	-7.3 (9.84)	-4.9 (5.84)	-1.1 (8.89)

Primary outcome: Change in Respiratory Rate

Time frame: Baseline to Day 28. Mean (Standard Deviation). Unit: breaths/minute

Measure	AG10 400mg n = 16	AG10 800mg n = 16	Placebo n = 17
Change in Respiratory Rate from Baseline to Day 28 (Predose)	-0.1 (2.23)	-0.8 (3.12)	-0.4 (2.35)
Change in Respiratory Rate from Baseline to Day 28 (Postdose)	-0.7 (1.68)	-1.1 (3.11)	-1.1 (2.93)

Primary outcome: Change in Temperature

Time frame: Baseline to Day 28. Mean (Standard Deviation). Unit: degrees Celsius

Measure	AG10 400mg n = 16	AG10 800mg n = 16	Placebo n = 17
Change in Temperature from Baseline to Day 28 (Predose)	0.17 (0.793)	0.06 (0.316)	-0.08 (0.506)
Change in Temperature from Baseline to Day 28 (Postdose)	0.22 (0.781)	-0.02 (0.357)	0.02 (0.194)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Onset date on or after first dose of study drug and not more than 30 days after last dose of study drug, up to day 58.. Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AG10 400mg	1 of 16 (6.3%)	10 of 16 (62.5%)	0 of 16
AG10 800mg	0 of 16 (0%)	11 of 16 (68.8%)	0 of 16
Placebo	2 of 17 (11.8%)	15 of 17 (88.2%)	0 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42389794Testani JM, Judge DP, Borlaug BA, Cherney D, Cox ZL, Gillmore JD, Lewis JB, Adler SH, Cao X, Castano A, Fox JC, Katz L, Mathur V, Xiong K, Butler J, Masri A. Effects of Acoramidis on Kidney Function in Transthyretin Amyloid Cardiomyopathy. Circ Heart Fail. 2026 Jul 2:e014656. doi: 10.1161/CIRCHEARTFAILURE.126.014656. Online ahead of print.
Derived from this study: PubMed 30885685Judge 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.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MARK MCGOVERN, RN study director

Eidos Therapeutics, a BridgeBio company

13 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AG10 in people with Familial ATTR-CM (ATTRm-CM, or FAC) and Wild-type ATTR-CM (ATTRwt-CM), run by Eidos Therapeutics, a BridgeBio company at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Diastolic Blood Pressure (time frame: Baseline to Day 28). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03458130, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2022.