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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT06128629
Recruitment Status : Recruiting
First Posted : November 13, 2023
Last Update Posted : May 14, 2024
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 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)
Actual Study Start Date : December 13, 2023
Estimated Primary Completion Date : December 2027
Estimated Study Completion Date : April 2028

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

Primary Outcome Measures :
  1. Composite outcome of cardiovascular (CV) mortality and CV events [ Time Frame: 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 :
  1. Change in baseline to month 18 in serum TTR [ Time Frame: Baseline, Month 18 ]
  2. Change from baseline to month 18 in KCCQ-OS score [ Time Frame: Baseline, Month 18 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT06128629

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Contact: Trial Manager at Intellia 1-857-285-6200 ext 6

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Sponsors and Collaborators
Intellia Therapeutics
Regeneron Pharmaceuticals
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Responsible Party: Intellia Therapeutics Identifier: NCT06128629    
Other Study ID Numbers: ITL-2001-CL-301
First Posted: November 13, 2023    Key Record Dates
Last Update Posted: May 14, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Intellia Therapeutics:
TTR-mediated amyloidosis
Amyloidosis, Hereditary
Amyloidosis, Hereditary, Transthyretin-Related Amyloidosis
Transthyretin amyloid cardiomyopathy
TTR cardiomyopathy
Wild-type TTR
Amyloidosis, Wild Type
Additional relevant MeSH terms:
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Amyloid Neuropathies, Familial
Heart Diseases
Cardiovascular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Amyloid Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors