Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy

(ATTRibute-CM Trial)

Recruiting at 102 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eidos Therapeutics, a BridgeBio company

Must not be taking: Calcium channel blockers

Disqualifiers: Acute myocardial infarction, Stroke, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 30 months

632 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications for ATTR-CM and calcium channel blockers like verapamil and diltiazem. However, you can continue using dihydropyridine calcium channel blockers and digitalis if needed for specific heart conditions.

What safety data exists for the treatment known as acoramidis or Placebo Oral Tablet?

The available research articles do not provide specific safety data for acoramidis or Placebo Oral Tablet. They discuss general drug safety databases and adverse drug reactions but do not mention these treatments directly. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests acoramidis, a pill taken regularly, in patients with ATTR-CM, a heart condition caused by protein buildup. The drug aims to prevent these proteins from clumping together and damaging the heart.

Eligibility Criteria

Inclusion Criteria

You have had heart failure in the past and were hospitalized for it, or you currently have symptoms and are being treated with a diuretic medication.

You have symptoms of heart disease categorized as NYHA Class I-III due to ATTR cardiomyopathy.

On stable doses of cardiovascular medical therapy

Exclusion Criteria

You are taking certain types of calcium channel blockers that affect your heart's conduction system, such as verapamil or diltiazem. However, if you are taking dihydropyridine calcium channel blockers or digitalis to manage atrial fibrillation with rapid ventricular response, you may be eligible.

Biomarkers of myocardial wall stress, NT-proBNP level ≥8500 pg/mL at screening

Measure of kidney function, eGFR by MDRD formula <15 mL/min/1.73 m2

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acoramidis HCl 800 mg or placebo twice daily for 30 months

30 months

Regular visits every 3 months for PK-PD substudy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of acoramidis treatment long-term without placebo

Long-term

Treatment Details

Interventions

• acoramidis
• Placebo Oral Tablet

Participant Groups

Group I: acoramidis HCl 800 mg Experimental Treatment 1 Intervention

Subjects will receive acoramidis HCl 800 mg twice daily. 6MWT primary outcome will be assessed at the end of 12 months. The hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP levels, and change from baseline in distance walked on the 6MWT will be assessed after 30 months of treatment.

Group II: Placebo Placebo Group 1 Intervention

Subjects will receive placebo to match twice daily. 6MWT primary outcome will be assessed at the end of 12 months. The hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP levels, and change from baseline in distance walked on the 6MWT will be assessed after 30 months of treatment.

Who Is Running the Clinical Trial?

Eidos Therapeutics, a BridgeBio company

Lead Sponsor

Trials

12

Recruited

2,400+

Findings from Research

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

The DIMDI provides comprehensive databases that contain valuable information on adverse drug reactions, which can help healthcare professionals and researchers understand the safety profiles of various medications.

Access to these databases is crucial for monitoring drug safety and improving patient care by identifying potential risks associated with drug treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Information on adverse drug reactions in databases hosted at the German Institute of Medical Documentation and Information (DIMDI)]. Bystrich, E.[2016]

In a clinical development program involving 1684 subjects and 2038 injections, OptiMARK demonstrated a safety profile comparable to Magnevist, with 31% of its injections associated with adverse events.

OptiMARK was found to be safe and well-tolerated, showing fewer adverse events compared to Magnevist (35%) and placebo (48%), indicating its potential as a reliable imaging agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The OptiMARK clinical development program: summary of safety data. Brown, JJ., Kristy, RM., Stevens, GR., et al.[2019]

The Drug Adverse Reaction Database (DART) provides detailed information on 147 confirmed and 89 potential protein targets associated with adverse drug reactions (ADRs), which is crucial for understanding the mechanisms behind these reactions and aiding in drug discovery.

DART includes extensive data on 257 drugs and 1080 ligands, offering insights into their binding properties, physiological functions, and the specific adverse effects they may cause, making it a valuable resource for researchers and developers in pharmacology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Adverse Reaction Target Database (DART) : proteins related to adverse drug reactions. Ji, ZL., Han, LY., Yap, CW., et al.[2018]

The study found a high overlap of safety signals (SDRs) among the EudraVigilance Data Analysis System (EVDAS), FAERS, and VigiBase® databases, with median overlaps of 85% at the Preferred Term level and up to 97.7% when combining High Level Terms with Standardized MedDRA® Queries.

Despite the high overlap, the recall of signals in EVDAS was only about 59.4% to 87.9% of all signals generated across the databases, indicating that while the databases share many similar safety profiles, there are still differences in reporting that can affect signal detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase&#174;. Vogel, U., van Stekelenborg, J., Dreyfus, B., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

[Information on adverse drug reactions in databases hosted at the German Institute of Medical Documentation and Information (DIMDI)]. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

The OptiMARK clinical development program: summary of safety data. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Drug Adverse Reaction Target Database (DART) : proteins related to adverse drug reactions. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase&#174;. [2021]