Open-Label Safety Study of Acoramidis (AG10) in Symptomatic ATTR Participants

Study Overview
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Brief Summary
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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 (AG10-301)

Detailed Description
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The primary objective of this prospective multi-center, open-label study is to evaluate the long-term safety and tolerability of acoramidis in the context of background heart failure therapy. Selected secondary efficacy endpoints and exploratory pharmacokinetic, pharmacodynamic/biomarker endpoints may also be assessed. All participants who complete 30 months of blinded study treatment and the Month 30 assessments of the double-blind treatment period of the Phase 3 ATTRibute-CM trial (AG10-301) may be eligible to participate in this Open Label Extension (OLE) study of acoramidis. The Day 1 visit in Study AG10-304 may be the same day as the Month 30 visit in Study AG10-301. Under these circumstances, the last dose of Investigational Medicinal Product (IMP) in Study AG10-301 will be the night before the day of the Month 30 visit and the first dose of acoramidis in Study AG10-304 will be during the Study AG10-304 Day 1 visit after baseline assessments have been completed. Currently, tafamidis is approved for the treatment of ATTR-CM in some regions. Participants are not allowed to be treated with tafamidis or any other ATTR-CM-specific approved or investigational treatments, or therapies used off-label or as non-prescription supplements for ATTR-CM at any time during the study. If participants choose treatment with a prohibited medication, they may be asked to discontinue acoramidis and they may be asked to discontinue/withdraw from the study. Under these circumstances, participants will be asked to complete an early termination visit, and a follow-up visit prior to discontinuation/withdrawal. Participants are not permitted to participate in another interventional clinical trial (with the exception of Study AG10-301) within 30 days prior to dosing and throughout Study AG10-304. Participants who choose to participate in another interventional clinical trial may be asked to withdraw from acoramidis and/or the study. In such cases, participants will be asked to complete an early termination visit and a follow-up visit. Participation in observational and/or registry studies should be discussed with the Medical Monitor.

Official Title
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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 (AG10-301)

Conditions
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Amyloid Cardiomyopathy, Transthyretin-Related

Intervention / Treatment
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* Drug: Acoramidis (AG10)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed 30 months of the blinded study treatment in Study AG10-301 and the Study AG10-301 Month 30 visit including assessments and procedures. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. 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. Exclusion Criteria: Acute myocardial infarction, acute coronary syndrome or coronary revascularization within 90 days prior to Day 1 stroke or transient ischemic attack (TIA) within 90 days prior to Day 1. Has hemodynamic instability, that in the judgment of the Investigator, would pose too great a risk for participation in the study. Has had a heart and/or liver transplant or is on the heart transplantation list within the year prior to Day 1 Has had implantation of a cardiac mechanical assist device (CMAD) or is scheduled for implantation of a CMAD Has confirmed diagnosis of light-chain (AL) amyloidosis at any time during Study AG10-301. Has estimated glomerular filtration rate (eGFR) by modification of diet for renal disease (MDRD) formula < 15 mL/min/1.73 m2 at Month 27 of Study AG10-301 or at any subsequent central lab value prior to Day 1. Known hypersensitivity to acoramidis, its metabolites, or formulation excipients. 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. 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. 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. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label study extension study from the AG10-301 double-blind study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AG10<br>Open-label study all participants will receive AG10 during this study. | Drug: Acoramidis (AG10)<br>* Acoramidis (AG10) twice daily<br>* Other names: ALXN 2060;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent Adverse Events [Safety and Tolerability] | Incidence of each treatment-emergent adverse events measured over 60 Months or study completion | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate all-cause mortality and cardiovascular mortality | Assessment of All-cause mortality and CV mortality during study period | 60 months | 
| Evaluate the effect of acoramidis on the 6-minute walk test (6MWT) | Change from Baseline in distance walked during the 6MWT during study period | 60 months | 
| Evaluate the effect of acoramidis on health-related quality of life Kansas City Cardiomyopathy Questionnaire | Change from Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score during study period [scale is scored from 0-100, where 0=Poor, 100=Excellent] | 60 months | 
| Evaluate the effect of acoramidis on the frequency of CV-related hospitalization | assess CV-related hospitalization during the study period | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ATTR-CM