Transthyretin Amyloidosis (ATTR) With CardiomyopathyPhase 3NCT06128629
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
A Phase 3 study testing NTLA-2001 in people with Transthyretin Amyloidosis (ATTR) With Cardiomyopathy, run by Intellia Therapeutics at 132 sites in 26 countries.
Trial summary
To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
- What is being tested?
- NTLA-2001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,200 participants
- Where
- 132 sitesin 26 countries
- Study dates
- 13 Dec 2023to Apr 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
132 sites in 26 countries. Contact the study team or a site near you to ask about taking part.
132 sites in 26 countries
United States38 sites, 37 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
- Recruiting
Emory University School of Medicine
Atlanta, Georgia, 30322
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Recruiting
Boston University School of Medicine
Boston, Massachusetts, 02118
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
- Recruiting
Northwestern University
Chicago, Illinois, 60611
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Recruiting
Ohio Health Research Institute
Columbus, Ohio, 43214
- Recruiting
Baylor Scott & White Research Institute
Dallas, Texas, 75201
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
- Recruiting
University of Colorado Denver
Denver, Colorado, 80045
- Withdrawn
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
- Recruiting
INOVA Fairfax Hospital
Falls Church, Virginia, 22042
- Recruiting
Baylor College of Medicine
Houston, Texas, 77030
- Recruiting
Houston Methodist Hospital
Houston, Texas, 77030
- Recruiting
Indiana University Health
Indianapolis, Indiana, 46202
- Recruiting
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
- Recruiting
St. Luke's Hospital
Kansas City, Missouri, 64111
- Recruiting
University of Kentucky Gill Heart Institute
Lexington, Kentucky, 40536
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
- Recruiting
Western Greater Los Angeles VA Medical Center
Los Angeles, California, 90073
- Recruiting
Yale University School of Medicine
New Haven, Connecticut, 06510
- Recruiting
New York University (NYU) School of Medicine - Langone Medical Center
New York, New York, 10016
- Recruiting
Columbia University Medical Center
New York, New York, 10032
- Recruiting
Stanford University
Palo Alto, California, 94305
- Recruiting
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
- Recruiting
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
- Recruiting
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15219
- Recruiting
Baylor Scott and White - The Heart Hospital Baylor Plano
Plano, Texas, 75093
- Recruiting
Oregon Health and Science University (OHSU)
Portland, Oregon, 97239
- Recruiting
Virginia Commonwealth University - Department of Internal Medicine
Richmond, Virginia, 23298
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
- Recruiting
University of California, San Diego (UCSD) - Medical Center
San Diego, California, 92103
- Recruiting
University of Arizona
Tucson, Arizona, 85724
- Recruiting
MedStar Washington Hospital Center - MedStar Heart and Vascular Institute
Washington D.C., District of Columbia, 20010
- Recruiting
Cleveland Clinic of Florida
Weston, Florida, 33331
Brazil9 sites, 9 recruiting
- Recruiting
Centro de Pesquisa NUPEC - Instituto Orizonti em Belo Horizonte
Belo Horizonte
- Recruiting
Complexo Hospitalar de Niterói (CHN-DASA)
Niterói
- Recruiting
CAPED - Centro Avancado de Pesquisa
Ribeirão Preto
- Recruiting
HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
Ribeirão Preto
- Recruiting
Cardiopulmonar da Bahia S. A. (Hospital Cardio Pulmonar)
Salvador
- Recruiting
Hospital Israelita Albert Einstein
São Paulo
- Recruiting
Instituto Dante Pazzanese de Cardiologia
São Paulo
- Recruiting
Instituto do Coracao (InCor) do Hospital das Clinicas da FMUSP
São Paulo
- Recruiting
PSEG Centro de Pesquisa Clinica S.A.
São Paulo
Australia8 sites, 7 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide
- Recruiting
Eastern Health - Box Hill Hospital
Box Hill, Victoria
- Withdrawn
Cairns Hospital
Cairns, Queensland
- Recruiting
The Canberra Hospital
Garran, Australian Capital Territory
- Recruiting
The Alfred Hospital
Melbourne
- Recruiting
Fiona Stanley Hospital
Perth, Western Australia
- Recruiting
Westmead Hospital
Westmead, New South Wales
- Recruiting
Princess Alexandra Hospital
Woolloongabba
Italy7 sites, 7 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
Bologna
- Recruiting
Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna
Cona
- Recruiting
Azienda Ospedaliero-Universitaria Careggi
Florence
- Recruiting
Ospedale Policlinico San Martino IRCCS
Genova
- Recruiting
Fondazione IRCCS Policlinico San Matteo
Pavia
- Recruiting
Fondazione Toscana Gabriele Monasterio per la Ricerca Medica
Pisa
- Recruiting
Azienda sanitaria universitaria Giuliano Isontina (ASU GI) - Ospedale di Cattinara
Trieste
United Kingdom7 sites, 1 recruiting
- Active, not recruiting
Synexus Midlands Clinical Research Centre
Birmingham
- Active, not recruiting
Synexus Wales Clinical Research Centre
Cardiff
- Active, not recruiting
Synexus Scotland Clinical Research Centre
Glasgow
- Active, not recruiting
Synexus Hexham Clinical Research Centre
Hexham
- Active, not recruiting
Synexus Merseyside Clinical Research Centre
Liverpool
- Recruiting
Richmond Pharmacology
London
- Active, not recruiting
Synexus Manchester Clinical Research Centre
Manchester
Argentina6 sites, 6 recruiting
- Recruiting
Fundacion Favalro
Buenos Aires
- Recruiting
Hospital Italiano de Buenos Aires
Buenos Aires
- Recruiting
ICBA
Buenos Aires
- Recruiting
Fundacion Favaloro
Ciudad Autonoma de Buenos Aire
- Recruiting
Hospital Italiano de Buenos Aires
Ciudad Autonoma de Buenos Aire
- Recruiting
Hospital Privado de Rosario
Rosario
Spain6 sites, 6 recruiting
- Recruiting
Hospital Universitario de A Coruna
A Coruña
- Recruiting
Hospital Universitari de Bellvitge
Barcelona
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona
- Recruiting
Hospital Universitario Puerta de Hierro
Majadahonda
- Recruiting
Hospital Universitario Virgen de la Victoria
Málaga
- Recruiting
Hospital Universitario Son Llatzer
Palma de Mallorca
Belgium5 sites, 5 recruiting
- Recruiting
AZ Sint-Jan Brugge
Bruges
- Recruiting
Universite Libre de Bruxelles (ULB) - Hopital Erasme
Brussels
- Recruiting
Antwerp University Hospital
Edegem
- Recruiting
UZ Leuven
Leuven
- Recruiting
Centre Hospitalier Regional de la Citadelle
Liège
France5 sites, 5 recruiting
- Recruiting
AP-HP Hopital Henri Mondor
Créteil
- Recruiting
AP-HM - Hopital de la Timone
Marseille
- Recruiting
AP-HP Hopital Bichat - Claude Bernard
Paris
- Recruiting
CHU Rennes - Hopital Pontchaillou
Rennes
- Recruiting
CHU de Toulouse - Hopital Rangueil
Toulouse
Canada4 sites, 4 recruiting
- Recruiting
Alberta Health Services - University of Calgary
Calgary, Alberta
- Recruiting
McGill University Health Centre
Montreal, Quebec
- Recruiting
University Health Network - Toronto General Hospital
Toronto, Ontario
- Recruiting
Vancouver Coastal Health Research Institute
Vancouver, British Columbia
Germany4 sites, 4 recruiting
- Recruiting
Charite Universitaetsmedizin Berlin
Berlin
- Recruiting
Universitaetsklinikum Essen
Essen
- Recruiting
Universitaetsklinikum Heidelberg
Heidelberg
- Recruiting
Universitaetsklinikum Wuerzburg
Würzburg
Japan4 sites, 4 recruiting
- Recruiting
Kumamoto University Hospital
Kumamoto
- Recruiting
National Cerebral and Cardiovascular Center
Osaka
- Recruiting
The University of Tokyo Hospital
Tokyo
- Recruiting
Toyama University Hospital
Toyama
South Korea4 sites
- Withdrawn
Chonnam National University Hospital
Gwangju
- Withdrawn
Samsung Medical Center
Seoul
- Withdrawn
Seoul National University Hospital
Seoul
- Withdrawn
Severance Hospital, Yonsei University Health System
Seoul
Israel3 sites, 3 recruiting
- Recruiting
Rambam Health Care Campus
Haifa
- Recruiting
Hadassah University Hospital, Ein Karem
Jerusalem
- Recruiting
Sheba Medical Center
Tel Litwinsky
Netherlands3 sites, 3 recruiting
- Recruiting
University Medical Center
Groningen
- Recruiting
Erasmus MC
Rotterdam
- Recruiting
Universitair Medisch Centrum Utrecht
Utrecht
Taiwan3 sites, 3 recruiting
- Recruiting
Far Eastern Memorial Hospital
New Taipei City
- Recruiting
National Taiwan University Hospital
Taipei
- Recruiting
Taipai Veterans General Hospital
Taipei
Austria2 sites, 2 recruiting
- Recruiting
Medizinische Universitaet Innsbruck
Innsbruck
- Recruiting
Universitaesklinikum St. Poelten
Sankt Pölten
Denmark2 sites, 2 recruiting
- Recruiting
Aarhus University Hospital
Aarhus
- Recruiting
Rigshospitalet
Copenhagen
New Zealand2 sites, 2 recruiting
- Recruiting
New Zealand Clinical Research
Auckland
- Recruiting
New Zealand Clinical Research
Christchurch
Portugal2 sites, 2 recruiting
- Recruiting
Centro Hospitalar Universitario de Lisboa Norte
Lisbon
- Recruiting
Centro Hospitalar Universitario do Porto
Porto
Singapore2 sites, 2 recruiting
- Recruiting
National Heart Centre
Singapore
- Recruiting
National University Hospital
Singapore
Sweden2 sites, 2 recruiting
- Recruiting
Karolinska University Hospital
Stockholm
- Recruiting
University Hospital of Umea
Umeå
Czechia1 site, 1 recruiting
- Recruiting
Fakultni nemocnice u sv. Anny v Brne
Brno
Hungary1 site, 1 recruiting
- Recruiting
Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika
Budapest
Mexico1 site, 1 recruiting
- Recruiting
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City
Norway1 site, 1 recruiting
- Recruiting
Oslo University Hospital - Rikshospitalet
Oslo
About this study
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)
To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.
Read the 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.
- Being tested
- NTLA-2001, Placebo
- 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
- Medical subject headings
- Amyloidosis, Hereditary, Transthyretin-Related, Amyloidosis, Cardiomyopathies, Amyloidosis, Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NTLA-2001Biological
NTLA-2001 (55mg) by IV infusion
PlaceboDrug
Normal saline (0.9% NaCl) by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| NTLA-2001 | Experimental | Single intravenous (IV) infusion of NTLA-2001 Receives: Biological: NTLA-2001 |
| Placebo | Placebo comparator | Single IV infusion of normal saline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome of cardiovascular (CV) mortality and CV events
Measured: Maximum study duration is dependent on event rates and is estimated to be at least 18 months and up to approximately 5 years
Secondary outcomes (2)
Change in baseline to month 18 in serum TTR
Measured: Baseline, Month 18
Change from baseline to month 18 in KCCQ-OS score
Measured: Baseline, Month 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start13 Dec 2023
- Primary completionDec 2027 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin Amyloidosis (ATTR) With CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a 2:1 ratio to NTLA-2001 or placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Intellia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06128629
- Sponsor's protocol ID
- ITL-2001-CL-301
- Status last verified
- Mar 2026
- First submitted
- 8 Nov 2023
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No