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

Purpose

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

Condition

  • Transthyretin Amyloidosis (ATTR) with Cardiomyopathy

Eligibility

Eligible Ages
Between 18 Years and 90 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Participants will be randomized in a 2:1 ratio to NTLA-2001 or placebo
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
NTLA-2001 		Single intravenous (IV) infusion of NTLA-2001
  • Biological: NTLA-2001
    NTLA-2001 (55mg) by IV infusion
Placebo Comparator
Placebo 		Single IV infusion of normal saline
  • Drug: Placebo
    Normal saline (0.9% NaCl) by IV infusion

Recruiting Locations

Boston University School of Medicine
Boston, Massachusetts 02118

More Details

Status
Recruiting
Sponsor
Intellia Therapeutics

Study Contact

Trial Manager at Intellia
1-857-285-6200
medicalinformation@intelliatx.com

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.