Study of ALXN2220 Versus Placebo in Adults With ATTR-CM

Study Overview
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Brief Summary
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The primary objective of this study is to assess the efficacy of ALXN2220 in the treatment of adult participants with ATTR-CM by evaluating the difference between the ALXN2220 and placebo groups as assessed by the composite endpoint of all-cause mortality (ACM) and total cardiovascular (CV) clinical events.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Amyloid Depleter ALXN2220 in Adult Participants With Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Conditions
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Transthyretin Amyloid Cardiomyopathy

Intervention / Treatment
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* Drug: ALXN2220
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Centrally confirmed diagnosis of ATTR-CM with either wild-type or variant TTR genotype End-diastolic interventricular septal wall thickness ≥ 11 mm for women or ≥ 12 mm for men on echocardiography measured at Screening NT-proBNP > 2000 pg/mL at Screening Treatment with a loop diuretic for at least 30 days prior to Screening History of heart failure NYHA Class II-IV at Screening Life expectancy of ≥ 6 months as per the Investigator's judgment Males and females of childbearing ability must use contraception Exclusion Criteria: Known leptomeningeal amyloidosis Known light chain (AL) or secondary amyloidosis (AA), or any other form of systemic amyloidosis Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening Uncontrolled clinically significant cardiac arrhythmia, per Investigator's assessment LVEF < 30% on echocardiography Renal failure requiring dialysis or an eGFR < 20 mL/min/1.73 m2 at Screening Polyneuropathy with PND score IV

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN2220<br>Participants will receive weight-based dose of ALXN2220 via intravenous (IV) infusion every 4 weeks (q4w) for at least 24 months up to a maximum of 48 months. | Drug: ALXN2220<br>* Participants will receive ALXN2220 via IV infusion.<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo via IV infusion q4w for at least 24 months up to a maximum of 48 months. | Drug: Placebo<br>* Participants will receive placebo via IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Events of All-cause Mortality (ACM) and Total Cardiovascular (CV) Clinical Events |  | Month 24 to Month 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Events of ACM and Total Heart Failure (HF) |  | Month 24 to Month 48 | 
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS) at Month 24 |  | Baseline, Month 24 | 
| Time to CV-related Mortality |  | Month 24 to Month 48 | 
| Change from Baseline in Six-minute Walk Test (6MWT) to 24 Months |  | Baseline, Month 24 | 
| Rate of CV Clinical Events |  | Month 24 to Month 48 | 
| Time to ACM |  | Month 24 to Month 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyloid Depleter, ALXN2220, Transthyretin Amyloid Cardiomyopathy, Transthyretin amyloid (ATTR), Transthyretin (TTR), N-terminal pro b-type natriuretic peptide (NT-proBNP), NT-proBNP, Amyloidosis, ATTR-CM