MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
- Conditions
- Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
- Interventions
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 765
- 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
- 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
- Liver failure
- Uncontrolled blood pressure
- Unable or unwilling to take vitamin A supplementation for the duration of the study
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 (102)
AP-HP Hopital Henri Mondor
🇫🇷Créteil, France
AP-HM - Hopital de la Timone
🇫🇷Marseille, France
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
AP-HP Hopital Bichat - Claude Bernard
🇫🇷Paris, France
Charite Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
Rigshospitalet
🇩🇰Copenhagen, Denmark
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes, France
Aarhus University Hospital
🇩🇰Aarhus, Denmark
CHU de Toulouse - Hopital Rangueil
🇫🇷Toulouse, France
University of Arizona
🇺🇸Tucson, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Western Greater Los Angeles VA Medical Center
🇺🇸Los Angeles, California, United States
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
Indiana University Health
🇺🇸Indianapolis, Indiana, 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
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
St. Luke's Hospital
🇺🇸Kansas City, Missouri, 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
Duke University Medical Center
🇺🇸Durham, North Carolina, 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
Virginia Commonwealth University - Department of Internal Medicine
🇺🇸Richmond, Virginia, United States
Fundacion Favalro
🇦🇷Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Fundacion Favaloro
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Hospital Privado de Rosario
🇦🇷Rosario, 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
The Alfred Hospital
🇦🇺Melbourne, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Medizinische Universitaet Innsbruck
🇦🇹Innsbruck, Austria
Universitaesklinikum St. Poelten
🇦🇹St. Polten, Austria
Antwerp University Hospital
🇧🇪Edegem, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
🇧🇷Ribeirão Preto, Brazil
Instituto Dante Pazzanese de Cardiologia
🇧🇷São Paulo, Brazil
PSEG Centro de Pesquisa Clinica S.A.
🇧🇷São Paulo, Brazil
Alberta Health Services - University of Calgary
🇨🇦Calgary, Alberta, Canada
Vancouver Coastal Health Research Institute
🇨🇦Vancouver, British Columbia, Canada
University Health Network - Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czechia
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Würzburg, Germany
Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika
🇭🇺Budapest, Hungary
Rambam Health Care Campus
🇮🇱Haifa, Israel
Hadassah University Hospital, Ein Karem
🇮🇱Jerusalem, Israel
Sheba Medical Center
🇮🇱Tel HaShomer, Israel
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
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
🇲🇽Ciudad de mexico, Mexico
University Medical Center
🇳🇱Groningen, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
New Zealand Clinical Research
🇳🇿Christchurch, New Zealand
Oslo University Hospital - Rikshospitalet
🇳🇴Oslo, Norway
Centro Hospitalar Universitario de Lisboa Norte
🇵🇹Lisbon, Portugal
Centro Hospitalar Universitario do Porto
🇵🇹Porto, Portugal
National Heart Centre
🇸🇬Singapore, Singapore
National University Hospital
🇸🇬Singapore, Singapore
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Universitario Son Llatzer
🇪🇸Palma De Mallorca, 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