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NCT06128629PHASE3Recruiting

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

Intellia Therapeutics

Start Date

12/13/2023

Completion Date

4/1/2028

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 1200 participants, who will be randomized to receive a single infusion of either NTLA-2001 or placebo.

Eligibility Criteria

Age Range: 18 years to 90 years

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 * History of liver disease * Uncontrolled blood pressure * Unable or unwilling to take vitamin A supplementation for the duration of the study

Interventions

BIOLOGICAL

NTLA-2001

DRUG

Placebo

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Conditions

Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Locations

University of Arizona

Tucson, Arizona 85724

United States

Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

Western Greater Los Angeles VA Medical Center

Los Angeles, California 90073

United States

Stanford University

Palo Alto, California 94305

United States

University of California, San Diego (UCSD) - Medical Center

San Diego, California 92103

United States

University of Colorado Denver

Denver, Colorado 80045

United States

Yale University School of Medicine

New Haven, Connecticut 06510

United States

MedStar Washington Hospital Center - MedStar Heart and Vascular Institute

Washington D.C., District of Columbia 20010

United States

Mayo Clinic - Jacksonville

Jacksonville, Florida 32224

United States

Cleveland Clinic of Florida

Weston, Florida 33331

United States

Emory University School of Medicine

Atlanta, Georgia 30322

United States

Northwestern University

Chicago, Illinois 60611

United States

Indiana University Health

Indianapolis, Indiana 46202

United States

University of Kentucky Gill Heart Institute

Lexington, Kentucky 40536

United States

Johns Hopkins University

Baltimore, Maryland 21287

United States

Brigham and Women's Hospital

Boston, Massachusetts 02115

United States

Boston University School of Medicine

Boston, Massachusetts 02118

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

St. Luke's Hospital

Kansas City, Missouri 64111

United States

New York University (NYU) School of Medicine - Langone Medical Center

New York, New York 10016

United States

Columbia University Medical Center

New York, New York 10032

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Ohio Health Research Institute

Columbus, Ohio 43214

United States

Oregon Health and Science University (OHSU)

Portland, Oregon 97239

United States

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania 19104

United States

Allegheny General Hospital

Pittsburgh, Pennsylvania 15212

United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania 15219

United States

Medical University of South Carolina

Charleston, South Carolina 29425

United States

Baylor Scott & White Research Institute

Dallas, Texas 75201

United States

University of Texas Southwestern Medical Center

Dallas, Texas 75390

United States

Baylor College of Medicine

Houston, Texas 77030

United States

Houston Methodist Hospital

Houston, Texas 77030

United States

Baylor Scott and White - The Heart Hospital Baylor Plano

Plano, Texas 75093

United States

INOVA Fairfax Hospital

Falls Church, Virginia 22042

United States

Virginia Commonwealth University - Department of Internal Medicine

Richmond, Virginia 23298

United States

Fundacion Favalro

Buenos Aires,

Argentina

Hospital Italiano de Buenos Aires

Buenos Aires,

Argentina

ICBA

Buenos Aires,

Argentina

Fundacion Favaloro

Ciudad Autonoma de Buenos Aire,

Argentina

Hospital Italiano de Buenos Aires

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

Sankt Pölten,

Austria

AZ Sint-Jan Brugge

Bruges,

Belgium

Universite Libre de Bruxelles (ULB) - Hopital Erasme

Brussels,

Belgium

Antwerp University Hospital

Edegem,

Belgium

UZ Leuven

Leuven,

Belgium

Centre Hospitalier Regional de la Citadelle

Liège,

Belgium

Centro de Pesquisa NUPEC - Instituto Orizonti em Belo Horizonte

Belo Horizonte,

Brazil

Complexo Hospitalar de Niterói (CHN-DASA)

Niterói,

Brazil

CAPED - Centro Avancado de Pesquisa

Ribeirão Preto,

Brazil

HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto

Ribeirão Preto,

Brazil

Cardiopulmonar da Bahia S. A. (Hospital Cardio Pulmonar)

Salvador,

Brazil

Hospital Israelita Albert Einstein

São Paulo,

Brazil

Instituto Dante Pazzanese de Cardiologia

São Paulo,

Brazil

Instituto do Coracao (InCor) do Hospital das Clinicas da FMUSP

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

Montreal, Quebec

Canada

Fakultni nemocnice u sv. Anny v Brne

Brno,

Czechia

Aarhus University Hospital

Aarhus,

Denmark

Rigshospitalet

Copenhagen,

Denmark

AP-HP Hopital Henri Mondor

Créteil,

France

AP-HM - Hopital de la Timone

Marseille,

France

AP-HP Hopital Bichat - Claude Bernard

Paris,

France

CHU Rennes - Hopital Pontchaillou

Rennes,

France

CHU de Toulouse - Hopital Rangueil

Toulouse,

France

Charite Universitaetsmedizin Berlin

Berlin,

Germany

Universitaetsklinikum Essen

Essen,

Germany

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 Litwinsky,

Israel

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola

Bologna,

Italy

Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna

Cona,

Italy

Azienda Ospedaliero-Universitaria Careggi

Florence,

Italy

Ospedale Policlinico San Martino IRCCS

Genova,

Italy

Fondazione IRCCS Policlinico San Matteo

Pavia,

Italy

Fondazione Toscana Gabriele Monasterio per la Ricerca Medica

Pisa,

Italy

Azienda sanitaria universitaria Giuliano Isontina (ASU GI) - Ospedale di Cattinara

Trieste,

Italy

Kumamoto University Hospital

Kumamoto,

Japan

National Cerebral and Cardiovascular Center

Osaka,

Japan

The University of Tokyo Hospital

Tokyo,

Japan

Toyama University Hospital

Toyama,

Japan

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City,

Mexico

University Medical Center

Groningen,

Netherlands

Erasmus MC

Rotterdam,

Netherlands

Universitair Medisch Centrum Utrecht

Utrecht,

Netherlands

New Zealand Clinical Research

Auckland,

New Zealand

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

Chonnam National University Hospital

Gwangju,

South Korea

Samsung Medical Center

Seoul,

South Korea

Seoul National University Hospital

Seoul,

South Korea

Severance Hospital, Yonsei University Health System

Seoul,

South Korea

Hospital Universitario de A Coruna

A Coruña,

Spain

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

Umeå,

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