Clinical trial NCT06128629: MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Intellia Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2023-11-13
Enrollment: 765
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in a 2:1 ratio to NTLA-2001 or placebo
Primary purpose: TREATMENT

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.

Eligibility criteria: 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
* Liver failure
* Uncontrolled blood pressure
* Unable or unwilling to take vitamin A supplementation for the duration of the study

Primary outcomes:
measure: Composite outcome of cardiovascular (CV) mortality and CV events
timeFrame: Maximum study duration is dependent on event rates and is estimated to be at least 18 months and up to 48 months
Secondary outcomes:
measure: Change in baseline to month 18 in serum TTR
timeFrame: Baseline, Month 18
measure: Change from baseline to month 18 in KCCQ-OS score
timeFrame: Baseline, Month 18
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Western Greater Los Angeles VA Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center - MedStar Heart and Vascular Institute
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Gill Heart Institute
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: New York
country: United States
facility: New York University (NYU) School of Medicine - Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University (OHSU)
state: Oregon
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University - Department of Internal Medicine
state: Virginia
city: Buenos Aires
country: Argentina
facility: Fundacion Favalro
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Fundacion Favaloro
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Rosario
country: Argentina
facility: Hospital Privado de Rosario
city: Garran
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Health - Box Hill Hospital
state: Victoria
city: Perth
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: St. Polten
country: Austria
facility: Universitaesklinikum St. Poelten
city: Bruxelles
country: Belgium
facility: Universite Libre de Bruxelles (ULB) - Hopital Erasme
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Ribeirão Preto
country: Brazil
facility: HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
city: São Paulo
country: Brazil
facility: PSEG Centro de Pesquisa Clinica S.A.
city: Calgary
country: Canada
facility: Alberta Health Services - University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Research Institute
state: British Columbia
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Créteil
country: France
facility: AP-HP Hopital Henri Mondor
city: Marseille
country: France
facility: AP-HM - Hopital de la Timone
city: Paris
country: France
facility: AP-HP Hopital Bichat - Claude Bernard
city: Rennes
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Rangueil
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Würzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah University Hospital, Ein Karem
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino IRCCS
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio per la Ricerca Medica
city: Trieste
country: Italy
facility: Azienda sanitaria universitaria Giuliano Isontina (ASU GI) - Ospedale di Cattinara
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Osaka
country: Japan
facility: National Cerebral and Cardiovascular Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Ciudad de mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
city: Groningen
country: Netherlands
facility: University Medical Center
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research
city: Oslo
country: Norway
facility: Oslo University Hospital - Rikshospitalet
city: Lisbon
country: Portugal
facility: Centro Hospitalar Universitario de Lisboa Norte
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto
city: Singapore
country: Singapore
facility: National Heart Centre
city: Singapore
country: Singapore
facility: National University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Llatzer
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umea
country: Sweden
facility: University Hospital of Umea
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipai Veterans General Hospital
city: Birmingham
country: United Kingdom
facility: Synexus Midlands Clinical Research Centre
city: Cardiff
country: United Kingdom
facility: Synexus Wales Clinical Research Centre
city: Glasgow
country: United Kingdom
facility: Synexus Scotland Clinical Research Centre
city: Hexham
country: United Kingdom
facility: Synexus Hexham Clinical Research Centre
city: Liverpool
country: United Kingdom
facility: Synexus Merseyside Clinical Research Centre
city: London
country: United Kingdom
facility: Richmond Pharmacology
city: Manchester
country: United Kingdom
facility: Synexus Manchester Clinical Research Centre
Study officials:
References: