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The VITAL Amyloidosis Study, a Global Phase 3, Efficacy and Safety Study of NEOD001 in Patients With AL Amyloidosis

Phase 3
Terminated
Conditions
Primary Systemic (AL) Amyloidosis
Interventions
Other: Placebo
Registration Number
NCT02312206
Lead Sponsor
Prothena Biosciences Ltd.
Brief Summary

This is a multi-center, international, randomized, double-blind, placebo-controlled, two-arm efficacy and safety study in subjects newly diagnosed with AL amyloidosis. Subjects will remain on-study until study completion, which will occur when all primary endpoint events (all-cause mortality or cardiac hospitalizations) have been reached.

Detailed Description

This is a multi-center, international, randomized, double-blind, placebo-controlled, two-arm efficacy and safety study in subjects newly diagnosed with AL amyloidosis. Approximately 236 subjects will be enrolled in \~60 centers, with approximately 118 subjects per arm.

This is an event driven trial, therefore subjects will remain on-study until study completion, which will occur when all primary endpoint events (all-cause mortality or cardiac hospitalizations) have been reached. All subjects who discontinue will be followed until the last event is adjudicated. The estimated overall study duration is approximately 42 months, including the enrollment and treatment periods

Study drug will be administered once every 28 days as a 60-120 minute IV infusion.

First-line chemotherapy must be a bortezomib-containing regimen, with bortezomib administered weekly. The number of cycles of first-line chemotherapy that are administered are at the discretion of the Investigator, and subsequent chemotherapy regimens may be prescribed as per standard of care at the Investigator's discretion.

An independent Data Monitoring Committee (DMC) will review data on a regular basis.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
260
Inclusion Criteria
  1. Age ≥ 18 years
  2. Newly diagnosed, AL amyloidosis treatment naïve
  3. Bone marrow consistent with plasma cell dyscrasia
  4. Confirmed diagnosis of AL amyloidosis
  5. Cardiac involvement
  6. Planned first-line chemotherapy contains a proteasome-inhibiting agent administered weekly
  7. Adequate bone marrow reserve, hepatic and renal function

Key

Exclusion Criteria
  1. Non-AL amyloidosis
  2. Meets diagnostic criteria for symptomatic multiple myeloma
  3. Subject is eligible for and plans to undergo ASCT
  4. History of Grade ≥ 3 infusion-associated AEs or hypersensitivity to another monoclonal antibody, or known hypersensitivity to diphenhydramine or acetaminophen

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NEOD001NEOD00124 mg/kg (maximum dose of 2500 mg) of NEOD001 administered once every 28 days.
PlaceboPlaceboPlacebo will be administered as a 250 mL bag of normal saline once every 28 days.
Primary Outcome Measures
NameTimeMethod
Time to Composite of All-cause Mortality or Cardiac HospitalizationRandomization until the date of death or cardiac hospitalization, up to 32 months

Time to all-cause mortality death occurring after the first infusion of study drug or cardiac hospitalization as adjudicated by the CEC occurring at least 91 days after first infusion of study drug through last subject last visit, whichever came first

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (78)

CHU Dijon - Hopital du Bocage

🇫🇷

Dijon, France

Stanford Cancer Institute (SCI)

🇺🇸

Stanford, California, United States

Hopital de la Cote de Nacre Avenue

🇫🇷

Caen Cedex 9, France

Hopital Henri Mondor

🇫🇷

Creteil, France

Charite-Universitatsmedizin

🇩🇪

Berlin, Germany

Washington University in Saint Louis

🇺🇸

Saint Louis, Missouri, United States

Hôpital Pitié-Salpêtrière

🇫🇷

Paris, France

Azienda Ospedaliera Sant'Andrea, U.O.S.

🇮🇹

Rome, Italy

Service d'Hermatologie CHU de Poitiers

🇫🇷

Poitiers, France

Hospital Universitari Germans Trias i Pujol

🇪🇸

Badalona, Spain

Universitätsklinikum Essen

🇩🇪

Essen, Germany

Eastern Health (Box Hill Hospital)

🇦🇺

Box Hill, Australia

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

The University of Queensland-Princess Alexandra Hospital (PAH)

🇦🇺

Woolloongabba, Australia

Columbia University - College of Physicians & Surgeons

🇺🇸

New York, New York, United States

Hopitaux Lyon Sud

🇫🇷

Pierre-Benite Cedex, France

CHU Rennes, Service de Medecine Interne

🇫🇷

Rennes Cedex 2, France

University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre

🇬🇧

Bristol, United Kingdom

Policlinica San Matteo

🇮🇹

Pavia, Italy

Hôpital Dupuytren - CHU Limoges

🇫🇷

Limoges, France

Universitatsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Meir Medical Center

🇮🇱

Kfar Saba, Israel

Clínica Universidad de Navarra

🇪🇸

Pamplona, Nevarra, Spain

Hospital Universitario Puerta de Hierro - Maiadahonda

🇪🇸

Madrid, Spain

Policlinico S.Orsola Malpighi, Unita' Operativa di Ematologia

🇮🇹

Bologna, Italy

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

The Royal Free London NHS Foundation Trust-The Royal Free Hospital

🇬🇧

London, United Kingdom

NNUH NHS Foundation Trust - Norfolk and Norwich University Hospital

🇬🇧

Norwich, United Kingdom

Winship Cancer Institute of Emory University

🇺🇸

Atlanta, Georgia, United States

John Hopkins University School of Medicine

🇺🇸

Baltimore, Maryland, United States

University of Chicago Medicine

🇺🇸

Chicago, Illinois, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

The Cleveland Clinic - Main Campus

🇺🇸

Cleveland, Ohio, United States

Hospital of the University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

University of Pittsburg - Hillman Cancer Center

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Texas; MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Princess Margaret Cancer Research Centre

🇨🇦

Toronto, Ontario, Canada

Sylvester Cancer Center, University of Miami

🇺🇸

Miami, Florida, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Indiana University Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

City of Hope

🇺🇸

Duarte, California, United States

Radiant Research Northwestern University

🇺🇸

Chicago, Illinois, United States

Boston University School of Medicine

🇺🇸

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

🇺🇸

New York, New York, United States

Amyloidosis Clinic Cnr Darcy Road and Bridge St. Westmead

🇦🇺

Sydney, Australia

Hadassah University Medical Center

🇮🇱

Jerusalem, Israel

The Chaim Sheba Medical Center

🇮🇱

Ramat Gan, Israel

MTZ Clinical Research Sp. z o.o.

🇵🇱

Warszawa, Poland

University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital

🇬🇧

Birmingham, United Kingdom

Leicester Royal Infirmary

🇬🇧

Leicester, United Kingdom

Southampton General Hospital

🇬🇧

Southampton, United Kingdom

Rigshospitalet

🇩🇰

Copenhagen, Denmark

Universitatsklinikum Hamburg-Eppendorf (UKE)

🇩🇪

Hamburg, Germany

University of Washington

🇺🇸

Seattle, Washington, United States

University Medical Center Groningen

🇳🇱

Groningen, Netherlands

ZNA Stuivenberg

🇧🇪

Antwerpen, Belgium

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

University of Calgary-Southern Alberta Cancer Research Institute

🇨🇦

Calgary, Alberta, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

University Hospital of Patras

🇬🇷

Patra, Greece

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Universitair Medisch Centrum Utrecht

🇳🇱

Utrecht, Netherlands

Newark Beth Israel Medical Center

🇺🇸

Newark, New Jersey, United States

Alexandra General Hospital of Athens

🇬🇷

Athens, Greece

Universitatsklinik fur Innere Medizin 1 Kinische Abteilung fur Onkologie Aligemeines Krankenhaus - Universitatskliniken

🇦🇹

Wien, Austria

ULB Hopital Erasme

🇧🇪

Brussel, Belgium

UZ Gasthuisberg

🇧🇪

Leuven, Belgium

Mayo Clinic Arizona

🇺🇸

Scottsdale, Arizona, United States

Colorado Blood Cancer Institute

🇺🇸

Denver, Colorado, United States

Froedtert & Medical College of Wisconsin, Cancer Center-Froedtert Hospital

🇺🇸

Milwaukee, Wisconsin, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Ochsner Clinic Foundation

🇺🇸

New Orleans, Louisiana, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

University of North Carolina Chapel Hill Comprehensive Cancer Center

🇺🇸

Chapel Hill, North Carolina, United States

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