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

Intellia Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: Transthyretin Amyloidosis (ATTR) with Cardiomyopathy

Treatments: Drug: Placebo; Biological: NTLA-2001

Study type: Interventional

Funder types: Industry

Identifiers

NCT06128629

ITL-2001-CL-301

Details and patient eligibility

About

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

Full 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.

Enrollment: 765 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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 1000 pg/mL (or greater than or equal to 2000 pg/mL if participant has known atrial fibrillation)

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 within 6 months 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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765 participants in 2 patient groups, including a placebo group

NTLA-2001

Experimental group

Description:

Single intravenous (IV) infusion of NTLA-2001

Treatment:

Biological: NTLA-2001

Placebo

Placebo Comparator group

Description:

Single IV infusion of normal saline

Treatment:

Drug: Placebo