Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM) MedDRA version: 20.0 Level: LLT Classification code 10002020 Term: Amyloid cardiomyopathy System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: Acoramidis (AG10)
Product Code: AG10
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Acoramidis
CAS Number: 1446711-81-4
Other descriptive name: 3-(3-(3,5-DIMETHYL-1H-PYRAZ
Sponsors
Eidos Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible to participate in this OLE study, participants must meet all the following criteria: 1. Completed 30 months of the blinded study treatment in Study AG10-301 and the Study AG10-301 Month 30 visit including assessments and procedures. 2. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. 3. Female participants of childbearing potential 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 female of childbearing potential and has not had a vasectomy must agree to use a double-barrier method of birth control. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 535
Exclusion criteria
Exclusion criteria: Participants who meet any of the following criteria at the Day 1 visit will not be eligible to participate in the study: 1. Has hemodynamic instability, that in the judgment of the Investigator, would pose too great a risk for participation in the study. 2. Has had a heart and/or liver transplant within the year prior to Day 1. 3. Has had implantation of a cardiac mechanical assist device (CMAD). 4. Has confirmed diagnosis of light-chain (AL) amyloidosis at any time during Study AG10-301. 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. Known hypersensitivity to acoramidis, its metabolites, or formulation excipients. 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. Females who are pregnant or breastfeeding. A negative urine pregnancy test at the Day 1 visit and at each study visit are required for female participants of childbearing potential. 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. 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. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess safety and tolerability of acoramidis in participants with symptomatic transthyretin amyloid cardiomyopathy (ATTR-CM) ;Secondary Objective: - 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) - 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 ;Primary end point(s): 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;Timepoint(s) of evaluation of this end point: AEs: Month 0-60; ET, unscheduled visit Physical examination, Vital signs, ECG: Day 1, Month 1, Month 6-60 every 6 months, Month 61; ET, unscheduled visit, 30 days post last dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - All-cause mortality and CV mortality - Change from Baseline in distance walked during the 6MWT (6MWD) - Change from Baseline in KCCQ Overall Summary Score (KCCQ-OS) - CV-related hospitalization - Change from baseline in TTR level (an in vivo measure of TTR stabilization) - TTR stabilization measured in established ex vivo assays (FPE and Western blot) in the PK-PD substudy ;Timepoint(s) of evaluation of this end point: - All-cause mortality and CV mortality: Month 0-61 - Distance walked during the 6MWT: Day 1, Month 6, 12, 18, 24, 30, 36, 42, 48, 54, 60; ET, unscheduled visit - KCCQ will be obtained on Day 1, Month 1, Month 6, and every 6 months up to Month 60 during the study. KCCQ should be completed prior to the EQ-5D-5L and prior to conduction of the 6MWT at those visits during which a 6MWT is performed - CV-related hospitalization will be summarized by number of patients who have at least one CV-related hospitalization and the frequency of CV-related hospitalization; cumulative frequency of CV-related hospitalization: Month 0-61 | — |
Countries
Australia, Belgium, Brazil, Canada, Czechia, Czech Republic, Denmark, Greece, Ireland, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactClinical Operations
Eidos Therapeutics, Inc.
Outcome results
None listed