An Open-Label Extension and Safety Monitoring Study of Acoramidis(AG10) in Participants with Symptomatic Transthyretin Amyloid Cardiomyopathy Who Completed the Phase 3 ATTRibute-CM Trial (AG10301)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eidos Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

14 Feb 2022 → ongoing

Decision date (initial)

2024-08-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Eidos Therapeutics, Inc

External identifiers

EU CT number

2024-515092-36-00

EudraCT number

2020-005643-22

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess safety and tolerability of acoramidis in participants with symptomatic transthyretin amyloid cardiomyopathy (ATTR-CM)

Secondary objectives 2

1. 1. To evaluate the effect of acoramidis on: all-cause mortality (ACM) and cardiovascular (CV) mortality; the 6-minute walk test (6MWT); health-related quality of life (QoL) Kansas City Cardiomyopathy Questionnaire (KCCQ); the frequency of CV-related hospitalization (CVH)
2. 2. To assess the pharmacodynamic (PD) effects of acoramidis as assessed by •circulating TTR concentration as an in vivo biomarker of stabilization and •established ex vivo assays of TTR stabilization

Conditions and MedDRA coding

Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Completed 30 months of the blinded study treatment in Study AG10301 and the Study AG10-301 Month 30 visit including assessments and procedures.
2. 2. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
3. 3. Women of childbearing potential (WOCBP) who engage in heterosexual intercourse must agree to use a highly effective method of contraception beginning with enrollment and continuing for 30 days after the last dose of acoramidis. Female participants using oral contraceptives must agree to use an additional birth control method. While not considered highly effective, a double-barrier method is acceptable. A male participant who is sexually active with a women of childbearing potential and has not had a vasectomy must agree to use a double-barrier method of birth control.

Exclusion criteria 11

1. 1. Has hemodynamic instability, that in the judgment of the Investigator, would pose too great a risk for participation in the study.
2. 2. Has had a heart and/or liver transplant within the year prior to Day 1.
3. 3. Has had implantation of a cardiac mechanical assist device (CMAD).
4. 4. Has confirmed diagnosis of light-chain (AL) amyloidosis at any time during Study AG10-301.
5. 5. Is on dialysis or has a degree of renal impairment that in the opinion of the Investigator might jeopardize the participant's safety, increase their risk from participation, or interfere with the study.
6. 6. Known hypersensitivity to acoramidis, its metabolites, or formulation excipients.
7. 7. At the end of Study AG10-301 or at Day 1 of Study AG10-304 (or any time during the study), participant is on prohibited medication.
8. 8. Females who are pregnant or breastfeeding. A negative urine pregnancy test at the Day 1 visit and at each study visit are required for WOCBP.
9. 9. In the judgment of the Investigator or Medical Monitor, has any clinically important ongoing medical condition or laboratory abnormality or condition that might jeopardize the participant's safety, increase their risk from participation, or interfere with the study.
10. 10. Participation in another interventional clinical trial (with the exception of Study AG10-301) within 30 days prior to dosing. Participation in observational and/or registry studies should be discussed with the Medical Monitor.
11. 11. Has any condition that in the opinion of the Investigator or Medical Monitor would preclude compliance with the study protocol such as a history of substance abuse, alcoholism, or a psychiatric condition.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety parameters to be assessed: treatment- emergent serious adverse events (SAEs) and adverse events (AEs), AEs leading to treatment discontinuation, abnormal physical examination findings of clinical relevance, abnormal vital signs of clinical relevance, abnormal electrocardiogram (ECG) parameters of clinical relevance, and changes in clinical safety laboratory parameters of clinical relevance

Secondary endpoints 6

1. All-cause mortality and CV mortality
2. Change from Baseline in distance walked during the 6MWT (6MWD)
3. Change from Baseline in KCCQ Overall Summary Score (KCCQ-OS)
4. CV-related hospitalization
5. Change from baseline in TTR level (an in vivo measure of TTR stabilization)
6. TTR stabilization measured in established ex vivo assays (FPE and D39Western blot) in the PK-PD substudy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eidos Therapeutics Inc.

Sponsor organisation

Eidos Therapeutics Inc.

Address

1800 Owens Street Suite C1200

City

San Francisco

Postcode

94158-2584

Country

United States

Scientific contact point

Organisation

Eidos Therapeutics Inc.

Contact name

Clinical Operations

Public contact point

Organisation

Eidos Therapeutics Inc.

Contact name

Clinical Operations

Third parties 8

Locations

9 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications