MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)

Phase 3

Recruiting

• Conditions: Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
• Interventions: Biological: NTLA-2001; Drug: Placebo

• Registration Number: NCT06128629
• Lead Sponsor: Intellia Therapeutics

Brief Summary

To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.

Detailed Description

This is a multinational, multicenter, double-blind, placebo-controlled study in approximately 765 participants, who will be randomized to receive a single infusion of either NTLA-2001 or placebo.

Study Timeline

• Study First Submitted: 2023-11-08
• Study First Submitted QC: 2023-11-08
• Study First Posted: 2023-11-13
• Study Start: 2023-12-13
• Status Verified: 2025-06
• Last Update Submitted: 2025-07-28
• Last Update Posted: 2025-07-30
• Primary Completion: 2027-12
• Study Completion: 2028-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 765

Inclusion Criteria

• Documented diagnosis of ATTR amyloidosis with cardiomyopathy
• Medical history of heart failure (HF)
• Symptoms of HF are optimally managed and clinically stable within 28 days prior to administration of study intervention
• Screening NT-proBNP, a blood marker of HF severity, greater than or equal to 600 pg/mL and less than 10,000 pg/mL

Exclusion Criteria

• New York Heart Association (NYHA) Class IV HF
• Polyneuropathy Disability score of IV (confined to wheelchair or bed)
• Has hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
• History of active malignancy within 3 years prior to screening
• RNA silencer therapy (patisiran, inotersen and/or eplontersen) within 12 months prior to dosing. Any prior vutrisiran use is not allowed
• Initiation of tafamidis or acoramidis within 56 days prior to study dosing
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2
• Liver failure
• Uncontrolled blood pressure
• Unable or unwilling to take vitamin A supplementation for the duration of the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NTLA-2001	NTLA-2001	Single intravenous (IV) infusion of NTLA-2001
Placebo	Placebo	Single IV infusion of normal saline

Primary Outcome Measures

Name	Time	Method
Composite outcome of cardiovascular (CV) mortality and CV events	Maximum study duration is dependent on event rates and is estimated to be at least 18 months and up to 48 months

Secondary Outcome Measures

Name	Time	Method
Change in baseline to month 18 in serum TTR	Baseline, Month 18
Change from baseline to month 18 in KCCQ-OS score	Baseline, Month 18

Trial Locations

Locations (125)

Mayo Clinic - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Cleveland Clinic of Florida; 🇺🇸 Weston, Florida, United States

Baylor Scott and White - The Heart Hospital Baylor Plano; 🇺🇸 Plano, Texas, United States

INOVA Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

ICBA; 🇦🇷 Buenos Aires, Argentina

Centre Hospitalier Regional de la Citadelle; 🇧🇪 Liège, Belgium

Centro de Pesquisa NUPEC - Instituto Orizonti em Belo Horizonte; 🇧🇷 Belo Horizonte, Brazil

Complexo Hospitalar de Niterói (CHN-DASA); 🇧🇷 Niterói, Brazil

CAPED - Centro Avancado de Pesquisa; 🇧🇷 Ribeirão Preto, Brazil

Hospital Israelita Albert Einstein; 🇧🇷 São Paulo, Brazil

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