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

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)

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06128629

Enrollment

1200

Registered

2023-11-13

Start date

2023-12-13

Completion date

2028-04-01

Last updated

2026-03-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Keywords

TTR, Amyloidosis, Cardiomyopathy, NTLA-2001, ATTR-CM, Transthyretin, ATTR, TTR-mediated amyloidosis, Amyloidosis, Hereditary, Amyloidosis, Hereditary, Transthyretin-Related Amyloidosis, Transthyretin amyloid cardiomyopathy, TTR cardiomyopathy, Wild-type TTR, V122I, Amyloidosis, Wild Type, CRISPR/Cas9

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 1200 participants, who will be randomized to receive a single infusion of either NTLA-2001 or placebo.

Interventions

BIOLOGICALNTLA-2001

NTLA-2001 (55mg) by IV infusion

DRUGPlacebo

Normal saline (0.9% NaCl) by IV infusion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Intervention model description

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

Eligibility

Sex/Gender

ALL

Age

18 Years to 90 Years

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 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 * History of liver disease * Uncontrolled blood pressure * Unable or unwilling to take vitamin A supplementation for the duration of the study

Design outcomes

Primary

Measure	Time frame
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 approximately 5 years

Secondary

Measure	Time frame
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

Countries

Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Norway, Portugal, Singapore, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

CONTACTTrial Manager at Intellia

medicalinformation@intelliatx.com1-857-285-6200

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 28, 2026