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

Phase 3

Recruiting

• Conditions: Transthyretin Amyloidosis (ATTR) with Cardiomyopathy
• Interventions: Biological: NTLA-2001; Drug: Placebo

• Registration Number: NCT06128629
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2023-11-08
• Study First Submitted QC: 2023-11-08
• Study First Posted: 2023-11-13
• Study Start: 2023-12-13
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-19
• Primary Completion: 2027-12
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 765

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)

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NTLA-2001	NTLA-2001	Single intravenous (IV) infusion of NTLA-2001
Placebo	Placebo	Single IV infusion of normal saline

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (70)

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

Virginia Commonwealth University - Department of Internal Medicine; 🇺🇸 Richmond, Virginia, United States

Fundacion Favalro; 🇦🇷 Buenos Aires, Argentina

The Canberra Hospital; 🇦🇺 Garran, Australian Capital Territory, Australia

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Cairns Hospital; 🇦🇺 Cairns, Queensland, Australia

Eastern Health - Box Hill Hospital; 🇦🇺 Box Hill, Victoria, Australia

Fiona Stanley Hospital; 🇦🇺 Perth, Western Australia, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Alberta Health Services - University of Calgary; 🇨🇦 Calgary, Alberta, Canada

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

CHU Rennes - Hopital Pontchaillou; 🇫🇷 Rennes, France

CHU de Toulouse - Hopital Rangueil; 🇫🇷 Toulouse, France

Universitaetsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Azienda Ospedaliero-Universitaria Careggi; 🇮🇹 Firenze, Italy

Ospedale Policlinico San Martino IRCCS; 🇮🇹 Genova, Italy

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy

Azienda sanitaria universitaria Giuliano Isontina (ASU GI) - Ospedale di Cattinara; 🇮🇹 Trieste, Italy

New Zealand Clinical Research; 🇳🇿 Christchurch, New Zealand

National University Hospital; 🇸🇬 Singapore, Singapore

Hospital Universitari de Bellvitge; 🇪🇸 Barcelona, Spain

Hospital Universitario Puerta de Hierro; 🇪🇸 Majadahonda, Spain

Hospital Universitario Virgen de la Victoria; 🇪🇸 Málaga, Spain

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

University Hospital of Umea; 🇸🇪 Umea, Sweden

Far Eastern Memorial Hospital; 🇨🇳 New Taipei City, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Taipai Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Synexus Midlands Clinical Research Centre; 🇬🇧 Birmingham, United Kingdom

Synexus Wales Clinical Research Centre; 🇬🇧 Cardiff, United Kingdom

Synexus Scotland Clinical Research Centre; 🇬🇧 Glasgow, United Kingdom

Synexus Hexham Clinical Research Centre; 🇬🇧 Hexham, United Kingdom

Synexus Merseyside Clinical Research Centre; 🇬🇧 Liverpool, United Kingdom

Richmond Pharmacology; 🇬🇧 London, United Kingdom

Synexus Manchester Clinical Research Centre; 🇬🇧 Manchester, United Kingdom

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands

Centro Hospitalar Universitario de Lisboa Norte; 🇵🇹 Lisbon, Portugal

Centro Hospitalar Universitario do Porto; 🇵🇹 Porto, Portugal

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Western Greater Los Angeles VA Medical Center; 🇺🇸 Los Angeles, California, United States

Indiana University Health; 🇺🇸 Indianapolis, Indiana, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Hospital Italiano de Buenos Aires; 🇦🇷 Buenos Aires, Argentina

McGill University Health Centre; 🇨🇦 Montréal, Canada

Vancouver Coastal Health Research Insitute; 🇨🇦 Vancouver, Canada

AP-HP Hopital Henri Mondor; 🇫🇷 Créteil, France

Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika; 🇭🇺 Budapest, Hungary

Stanford University; 🇺🇸 Palo Alto, California, United States

University of Colorado Denver; 🇺🇸 Denver, Colorado, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

MedStar Washington Hospital Center - MedStar Heart and Vascular Institute; 🇺🇸 Washington, District of Columbia, United States

Emory University School of Medicine; 🇺🇸 Atlanta, Georgia, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Kentucky Gill Heart Institute; 🇺🇸 Lexington, Kentucky, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Boston University School of Medicine; 🇺🇸 Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

New York University (NYU) School of Medicine - Langone Medical Center; 🇺🇸 New York, New York, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Oregon Health and Science University (OHSU); 🇺🇸 Portland, Oregon, United States

Penn Presbyterian Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States