Clinical trial NCT02312206: The VITAL Amyloidosis Study, a Global Phase 3, Efficacy and Safety Study of NEOD001 in Patients With AL Amyloidosis
Official title: A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, 2-Arm, Efficacy and Safety Study of NEOD001 Plus Standard of Care Versus Placebo Plus Standard of Care in Subjects With Light Chain (AL) Amyloidosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Primary Systemic (AL) Amyloidosis
Lead sponsor: Prothena Biosciences Ltd.
Sponsor class: INDUSTRY
First posted: 2014-12-09
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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

Primary outcomes:
measure: Time to Composite of All-cause Mortality or Cardiac Hospitalization
timeFrame: Randomization until the date of death or cardiac hospitalization, up to 32 months
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute (SCI)
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: Sylvester Cancer Center, University of Miami
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: Radiant Research Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in Saint Louis
state: Missouri
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University - College of Physicians & Surgeons
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic - Main Campus
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburg - Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas; MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin, Cancer Center-Froedtert Hospital
state: Wisconsin
city: Box Hill
country: Australia
facility: Eastern Health (Box Hill Hospital)
city: Sydney
country: Australia
facility: Amyloidosis Clinic Cnr Darcy Road and Bridge St. Westmead
city: Woolloongabba
country: Australia
facility: The University of Queensland-Princess Alexandra Hospital (PAH)
city: Wien
country: Austria
facility: Universitatsklinik fur Innere Medizin 1 Kinische Abteilung fur Onkologie Aligemeines Krankenhaus - Universitatskliniken
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Brussel
country: Belgium
facility: ULB Hopital Erasme
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Calgary
country: Canada
facility: University of Calgary-Southern Alberta Cancer Research Institute
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Research Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Caen Cedex 9
country: France
facility: Hopital de la Cote de Nacre Avenue
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon - Hopital du Bocage
city: Limoges
country: France
facility: Hôpital Dupuytren - CHU Limoges
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Pierre-Benite Cedex
country: France
facility: Hopitaux Lyon Sud
city: Poitiers
country: France
facility: Service d'Hermatologie CHU de Poitiers
city: Rennes Cedex 2
country: France
facility: CHU Rennes, Service de Medecine Interne
city: Berlin
country: Germany
facility: Charite-Universitatsmedizin
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf (UKE)
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
city: Patra
country: Greece
facility: University Hospital of Patras
city: Jerusalem
country: Israel
facility: Hadassah University Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Policlinico S.Orsola Malpighi, Unita' Operativa di Ematologia
city: Pavia
country: Italy
facility: Policlinica San Matteo
city: Rome
country: Italy
facility: Azienda Ospedaliera Sant'Andrea, U.O.S.
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Nevarra
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Maiadahonda
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: The Royal Free London NHS Foundation Trust-The Royal Free Hospital
city: Norwich
country: United Kingdom
facility: NNUH NHS Foundation Trust - Norfolk and Norwich University Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: