Extension Study of ACT-EARLY

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], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-02-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Eidos Therapeutics Inc., a BridgeBio company

External identifiers

EU CT number

2024-513676-18-00

WHO UTN

U1111-1323-6219

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic

To evaluate the long-term safety and tolerability of acoramidis in participants with newly diagnosed ATTR-CM

Secondary objectives 7

1. 1. To evaluate the effect of acoramidis on all-cause mortality (ACM) and cardiovascular mortality (CVM)
2. 2. To evaluate the effect of acoramidis on cardiovascular-related hospitalization (CVH)
3. 3. To evaluate the effect of acoramidis on heart failure (HF) events, where HF events are described as: Outpatient HF event (O-HF), or Urgent visit for HF (UV-HF), or Hospitalization for HF (H-HF), or New Onset of HF (NOHF)
4. 4. To evaluate the effect of acoramidis on symptomatic ATTR-CM
5. 5. To evaluate the effect of acoramidis on arrhythmic and cardiac conduction complications
6. 6. To evaluate the effect of acoramidis on musculoskeletal complications
7. 7. To evaluate the effect of acoramidis on objective imaging and biomarker measures of interest

Conditions and MedDRA coding

Transthyretin Amyloidosis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Participants must have completed the AG10-501 study (ACT-EARLY study) within the past 60 calendar days with a diagnosis of ATTR-CM (based on the AG10-501 protocol definition of ATTR-CM).
2. 2. Participant must be willing and able to give signed informed consent for participation in the study. Informed consent must be obtained prior to initiation of study procedures.
3. 3. Agree to the use of highly effective contraception: a. FEMALE: WOCBP (defined as all women physiologically capable of becoming pregnant) who engage in heterosexual intercourse must agree to use a highly effective method of contraception from Day 1 and continuing for 30 calendar days after the last dose of study drug. (see Section 8.3.6). b. MALE: A male participant who has not had a vasectomy and is sexually active with a female of childbearing potential must agree to use a double-barrier method of birth control during the study and continue for 30 calendar days after the last dose of study drug. Males must agree to refrain from sperm donation for a minimum of 30 calendar days post the last dose of the study drug.

Exclusion criteria 12

1. 1. Participants who completed the AG10-501 study with a diagnosis of ATTR-PN only or who permanently discontinued IMP prior to diagnosis of ATTR-CM in AG10-501.
2. 2. History of light-chain amyloidosis (AL) or another non-TTR amyloid subtype (eg, ApoA 1, gelsolin).
3. 3. History of a monoclonal paraprotein or abnormal light chains in serum or urine (ie, MGUS) in which AL has not been ruled out.
4. 4. Stage IV or V chronic kidney disease (corresponding to an eGFR ≤ 29 mL/min/1.73 m2), or undergoing renal dialysis, or recipient of a kidney transplant.
5. 5. Active malignancy, except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix that has been successfully treated. In the event a participant developed a low-grade and treatable malignancy in the AG10-501 study (eg, low-grade, localized prostate cancer) and the decision by the Investigator at that time was to continue the participant in the AG10-501 study, that participant may still qualify for Study AG10504 after documentation with the Medical Monitor.
6. 6. History of any organ transplant (with the exception of corneal transplant).
7. 7. Known hypersensitivity to acoramidis or any of the excipients within the study drug.
8. 8. Treatment for ATTR-CM with any ATTR-oriented on- or off-label or OTC product.
9. 9. Female participants who are pregnant or breastfeeding. A negative urine pregnancy test on Day 1 prior to dosing is required for WOCBP. A positive urine dipstick pregnancy test will need to be confirmed with a serum test and participants cannot commence AG10-504 study unless the serum test results return negative.
10. 10. In the judgment of the Investigator or Medical Monitor, has any clinically relevant ongoing medical condition or laboratory abnormality or other condition that might jeopardize the participant’s safety, increase the participant’s risk from participation, interfere with the study, or confound study results.
11. 11. Participation in another investigational clinical trial. Participation in observational and/or registry studies must be discussed with the Medical Monitor.
12. 12. Major surgery planned during the next 6 months. For participants who may have required major surgery during their participation in the AG10-501 study and the decision by the Investigator at that time was to continue the participant in the AG10-501 study, that participant may still qualify for Study AG10-504 provided study participation does not interfere with the surgical care plan and vice versa.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants with: treatment-emergent AEs and SAEs, AEs leading to treatment discontinuation, abnormal physical examination findings of clinical relevance, abnormal vital signs of clinical relevance, abnormal ECG parameters ofclinical relevance, changes in clinical safety laboratory parameters of potential concern

Secondary endpoints 7

1. 1. All-cause mortality and cardiovascular mortality
2. 2. Cardiovascular-related hospitalization
3. 3. Participants with: • Any HF event: O-HF and/or UV-HF and/or H-HF • UV-HF and/or H-HF • O-HF • UV-HF • H-HF • NOHF
4. 4. Development of symptomatic ATTR-CM as defined by the investigator
5. 5. New arrhythmia and cardiac conduction complications (not otherwise attributable to a non-amyloid cause) as defined by: • New onset of atrial fibrillation or atrial flutter and/or • Sustained ventricular tachycardia or sudden cardiac death and/or • New onset 1st or 2nd degree atrioventricular block and/or • Conduction disease requiring temporary transvenous or permanent pacemaker implantation
6. 6. New diagnosis of or therapeutic surgery (not otherwise attributable to a non-amyloid cause) for: • Carpal tunnel syndrome and/or • Brachial biceps tendon rupture or Achilles tendon rupture and/or • Lumbar spinal stenosis and/or • Hip and knee osteoarthritis and/or • Trigger finger and/or • Rotator cuff osteoarthritis
7. 7. Change from baseline in: o Echocardiographic and strain parameters that estimate myocardial structure and function o NT-proBNP and hsTnI

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

Adam Castano

Public contact point

Organisation

Eidos Therapeutics Inc.

Contact name

Janine Dolan

Third parties 6

Locations

11 EU/EEA countries · 34 investigational sites

By country

Investigational sites

Results and documents

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

Documents 86 files

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

Application history

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