A Phase 3 Study of ALXN2060 in Japanese Participants With Symptomatic ATTR-CM

Study Overview
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Brief Summary
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This prospective study is designed to evaluate the efficacy, safety, and tolerability of ALXN2060 (also known as AG10), as well as to establish its pharmacokinetic and pharmacodynamic profile in Japanese participants with symptomatic ATTR-CM administered on a background of stable heart failure therapy.

Detailed Description
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Participants will receive ALXN2060 for 12 months (Part A). Following the last visit (Month 12) of Part A, participants will continue the study in Part B, which will last for an additional 18 months (30 months from Day 1), during which all participants will continue to receive oral treatment with ALXN2060. Following completion of Month 30 assessments in Part B, participants will be offered the opportunity to continue to receive ALXN2060 in the Extension Period, which will last until ALXN2060 is approved in Japan or for up to 24 additional months, whichever occurs first.

Official Title
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A Phase 3, Prospective, Multicenter, Open Label, 2-Part Study of the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of ALXN2060 in Japanese Participants With Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Conditions
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Symptomatic Transthyretin Amyloid Cardiomyopathy

Intervention / Treatment
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* Drug: ALXN2060


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of ATTR-CM with either wild-type TTR or a variant TTR genotype. History of heart failure evidenced by at least 1 prior hospitalization for heart failure or clinical evidence of heart failure without prior heart failure hospitalization manifested by signs or symptoms of volume overload or elevated pressures or heart failure symptoms that required or requires ongoing treatment with a diuretic. New York Heart Association Class I-III symptoms due to ATTR-CM. On stable doses of cardiovascular medical therapy. Completed ≥ 150 meters on the 6MWT on 2 tests prior to Day 1. Left ventricular (LV) wall (interventricular septum or LV posterior wall) thickness ≥ 12 millimeters. Biomarkers of myocardial wall stress: N-terminal pro-brain-type natriuretic pep (NT-proBNP) level ≥ 300 picograms/milliliter (pg/mL). Exclusion Criteria: Acute myocardial infarction, acute coronary syndrome or coronary revascularization, or experienced stroke or transient ischemic attack within 90 days prior to screening. Hemodynamic instability at screening. Likely to undergo heart transplantation within a year of screening. Current treatment with marketed drug products and other investigational agents for the treatment of ATTR-CM. Current treatment with calcium channel blockers with conduction system effects (for example, verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed. Confirmed diagnosis of light-chain (AL) amyloidosis. Biomarkers of myocardial wall stress: NT-ProBNP ≥ 8,500 pg/mL. Measure of kidney function, estimated glomerular filtration rate by Modification of Diet in Renal Disease formula < 30 mL/minute/1.73 meters squared.

Ages Eligible for Study
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Minimum Age: 20 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN2060<br>Participants will receive ALXN2060. | Drug: ALXN2060<br>* ALXN2060 tablets will be administered twice daily at a dose of 800 milligrams.<br>* Other names: Acoramidis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline To Month 12 Of Treatment In Distance Walked During The Six-minute Walk Test (6MWT) |  | Baseline, Month 12 | 
| All-cause Mortality And Cardiovascular-related Hospitalization Over A 30-month Period |  | Baseline through Month 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline To Month 30 Of Treatment In Distance Walked During The 6MWT |  | Baseline, Month 30 | 
| Change From Baseline To Month 12 Of Treatment In The Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) |  | Baseline, Month 12 | 
| Change From Baseline To Month 30 Of Treatment In The KCCQ-OS |  | Baseline, Month 30 | 
| Incidence Of Treatment-emergent Serious Adverse Events (SAEs) And Adverse Events (AEs) |  | Baseline through Month 12 | 
| Incidence Of Treatment-emergent SAEs And AEs |  | Baseline through Month 30 | 
| Change From Baseline To Day 28 In Transthyretin (TTR) Stabilization |  | Baseline, Day 28 | 
| Change From Baseline To Month 30 In TTR Stabilization |  | Baseline, Month 30 |