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

Sponsor

Intellia Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06128629

Collaborator

Regeneron Pharmaceuticals (Industry)

765

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy	Biological: NTLA-2001 Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

765 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized in a 2:1 ratio to NTLA-2001 or placeboParticipants will be randomized in a 2:1 ratio to NTLA-2001 or placebo

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

MAGNITUDE: A Phase 3, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2027

Anticipated Study Completion Date :

Apr 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts 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