A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients with AL Amyloidosis
- Conditions
- Light Chain (AL) Amyloidosis
- Interventions
- Registration Number
- NCT04973137
- Lead Sponsor
- Prothena Biosciences Ltd.
- Brief Summary
A Phase 3 study to evaluate the efficacy and safety of birtamimab plus standard of care compared to placebo plus standard of care in Mayo Stage IV patients with AL amyloidosis.
- Detailed Description
This is a Phase 3 multicenter, global, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of birtamimab in Mayo Stage IV patients with AL amyloidosis (i.e., Double-blind Phase), followed by a long-term, open-label extension (i.e., Open-label Extension \[OLE\] Phase). The primary objective of the Double-blind Phase is to evaluate the efficacy of birtamimab by assessing time to all-cause mortality. All patients will receive bortezomib-containing chemotherapy regimen as standard of care.
For the Double-blind Phase of the study, approximately 220 newly diagnosed Mayo Stage IV patients with AL amyloidosis will be enrolled and randomized in a 2:1 ratio to birtamimab or placebo. Subjects will remain on study until study completion, when the pre-defined number of events (all-cause mortality) have been reached.
After completion of the Double-blind Phase, eligible subjects may enter the optional OLE Phase, in which all subjects will receive open-label birtamimab treatment, regardless of Double-blind Phase randomized treatment assignment. Treatment in the OLE Phase will continue for an additional 24 months or until birtamimab is commercially available in a subject's country of residence, whichever occurs first (in accordance with country-specific regulations). The primary objective of the OLE Phase is to evaluate the long-term safety of birtamimab plus standard of care in Mayo Stage IV subjects with AL amyloidosis.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of study Standard of Care Chemotherapy Intravenous administration of 24 mg/kg birtamimab every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care. The initiation of daratumumab treatment at randomization is allowed at the discretion of the Investigator; initiation at any other time during the Double-blind Phase is prohibited. For subjects who did not initiate daratumumab at randomization during the Double-blind Phase, daratumumab may be initiated at any time during the OLE Phase at the Investigator's discretion. Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of study Standard of Care Chemotherapy Intravenous 0.9% Saline administration as a placebo every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator. Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of study Placebo Intravenous 0.9% Saline administration as a placebo every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator. Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of study Birtamimab Intravenous administration of 24 mg/kg birtamimab every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care. The initiation of daratumumab treatment at randomization is allowed at the discretion of the Investigator; initiation at any other time during the Double-blind Phase is prohibited. For subjects who did not initiate daratumumab at randomization during the Double-blind Phase, daratumumab may be initiated at any time during the OLE Phase at the Investigator's discretion.
- Primary Outcome Measures
Name Time Method Time to all-cause mortality for the Double Blind Phase Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached. Comparison of time to all-cause mortality for birtamimab and placebo control.
- Secondary Outcome Measures
Name Time Method 6MWT distance for the Double Blind Phase Month 9 Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance
Physical Component Summary score of the Short Form-36, version 2 for the Double Blind Phase Month 9 The Short Form-36, version 2 is a 36-item self-administered quality-of-life questionnaire that measures health on functional status, well-being, and overall evaluation of health. The Physical Component Summary score ranges from 0 to 100 with higher scores indicating higher health-related quality of life. The Physical Component Summary is derived primarily from questions regarding physical functioning, physical problems, bodily pain, and general health questions.
Trial Locations
- Locations (143)
University of California San Francisco
🇺🇸San Francisco, California, United States
St. Francis Hospital
🇺🇸Hartford, Connecticut, United States
Yale Cancer Center
🇺🇸North Haven, Connecticut, United States
Smilow Cancer Hospital Care Center at Trumbull
🇺🇸Trumbull, Connecticut, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Johns Hopkins University
🇺🇸Bethesda, Maryland, United States
Boston University School of Med.
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Perlmutter Cancer Center - 38th Street
🇺🇸New York, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
New York University Langone Hospital - Long Island
🇺🇸New York, New York, United States
Duke Clinical Research Institute
🇺🇸Durham, North Carolina, United States
Wake Forest Baptist Health - Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic Main Campus
🇺🇸Cleveland, Ohio, United States
The Ohio State University College of Medicine
🇺🇸Columbus, Ohio, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Vanderbilt - Ingram Cancer Center - Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
University of Washington
🇺🇸Seattle, Washington, United States
Froedtert and Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
SESLHD: St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Icon Cancer Centre - Wesley
🇦🇺Auchenflower, Queensland, Australia
Icon Cancer Center
🇦🇺South Brisbane, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Paracelsus Medical University
🇦🇹Salzburg, Austria
Medizinische Universität
🇦🇹Vienna, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
🇧🇪Oostende, Belgium
AZ Sint-Jan Brugge-Oostende AV
🇧🇪Oostende, Belgium
Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
🇧🇪Yvoir, Belgium
CHU UCL Namur (Site Godinne)
🇧🇪Yvoir, Belgium
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Royal Victoria Hospital
🇨🇦Montréal, Quebec, Canada
Fakultnà Nemocnice Brno
🇨🇿Brno, Jihormoravsky Kraj, Czechia
Fakultni nemocnice ostrava
🇨🇿Ostrava-Poruba, Moravian-Silesian, Czechia
Všeobecná fakultnà nemocnice v Praze
🇨🇿Praha, Prague, Czechia
Odense Universitetshospital
🇩🇰Odense, Syddanmark, Denmark
Hôpital Bretonneau
🇫🇷Tours Cedex 9, Centre, France
Hôpital Haut-Lévêque
🇫🇷Pessac, Gironde, France
Hopital Necker
🇫🇷Paris Cedex 15, Ill-de-France, France
Pitie-Salpêtrière Hospital
🇫🇷Paris, Ill-de-France, France
Hôpitaux de Brabois
🇫🇷Vandœuvre-lès-Nancy, Lorraine, France
Hopital Rangueil
🇫🇷Toulouse Cedex 9, Midi-Pyrenees, France
Hôpital Claude Huriez
🇫🇷Lille, Nord, France
CHU Nantes
🇫🇷Nantes, Pays de la Loire, France
Centre Hospitalier Universitaire Poitiers
🇫🇷Poitiers, Vienne, France
CHU de Bordeaux
🇫🇷Bordeaux, France
Hôpitaux Universitaires Henri Mondor
🇫🇷Créteil, France
Hopital Henri Mondor, Creteil
🇫🇷Créteil, France
Centre Hospitalier Universitaire Limoges
🇫🇷Limoges, France
Hôpital Necker-Enfants Malades
🇫🇷Paris, France
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Wuerttemberg, Germany
Uniklinik Köln
🇩🇪Köln, Baden-Württemberg, Germany
University Medicine Mainz
🇩🇪Mainz, Rheinland-Pfalz, Germany
Charité Campus Mitte
🇩🇪Berlin, Germany
Alexandra General Hospital
🇬🇷Athens, Attica, Greece
Theagenio Anti-Cancer Hospital of Thessaloniki
🇬🇷ThessalonÃki, Central Macedonia, Greece
University Hospital of Patras
🇬🇷Patra, Peloponnese, Greece
Pécsi Tudományegyetem Klinikai Központ
ðŸ‡ðŸ‡ºPécs, Baranya, Hungary
Szent-Györgyi Albert Klinikai Központ
ðŸ‡ðŸ‡ºSzeged, Csongrad, Hungary
Debreceni Egyetem Klinikai Központ
ðŸ‡ðŸ‡ºDebrecen, Hajdu-Bihar County, Hungary
Semmelweis Egyetem - I. sz. Belgyógyászati Klinika
ðŸ‡ðŸ‡ºBudapest, Hungary
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
ðŸ‡ðŸ‡ºBudapest, Hungary
Cork University Hospital
🇮🇪Cork, Munster, Ireland
Cancer Clinical Trials and Research Unit, Beaumont Hospital
🇮🇪Dublin, Ireland
Bnai Zion Medical Center
🇮🇱Haifa, Haifa District, Israel
Rambam Medical Center
🇮🇱Haifa, Haifa District, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Jerusalem District, Israel
Rabin Medical Center - Beilinson Hospital
🇮🇱Ashkelon, Southern District, Israel
Samson Assuta Ashdod Hospital
🇮🇱Ashdod, Israel
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Carmel Medical Center
🇮🇱Haifa, Israel
Azienda Ospedaliero Universitaria Ospedali Riuniti Di Ancona
🇮🇹Ancona, Italy
Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
🇮🇹Bologna, Italy
ASST Spedali Civili
🇮🇹Brescia, Italy
Azienda Ospedaliero Universitaria Policlinico Gaspare Rodolico - San Marco
🇮🇹Catania, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Azienda Ospedaliero-Universitaria Pisana
🇮🇹Pisa, Italy
Umberto I - Policlinico di Roma
🇮🇹Roma, Italy
Kyoto Kuramaguchi Medical Center
🇯🇵Kita, Kyoto, Japan
Shinshu University Hospital
🇯🇵Matsumoto, Nagano, Japan
Jichi medical university hospital
🇯🇵Shimotsuke, Tochigi, Japan
Tokushima University Hospital
🇯🇵Kuramoto, Tokushima, Japan
Red Cross Medical Center
🇯🇵Shibuya-ku, Tokyo, Japan
Nagoya City University Hospital
🇯🇵Aichi, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Keimyung University Dongsan Hospital
🇰🇷Daegu, Gyeongsangbugdo, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Gwangju, Jeollanam-do, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Seoul Teugbyeols, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Kosin University Gospel Hospital
🇰🇷Busan, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea - Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Maastricht Universitair Medisch Centrum
🇳🇱Maastricht, Limburg, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Klinika Hematologii i Transplantologii
🇵🇱Gdańsk, Pomorskie, Poland
Uniwersytecki Szpital Kliniczny Nr 1
🇵🇱Szczecin, Poland
Hospital de Braga
🇵🇹Braga, Portugal
Centro Hospitalar e Universitário de Coimbra
🇵🇹Coimbra, Portugal
Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria
🇵🇹Lisboa, Portugal
Hospital Universitario Son Espases
🇪🇸Palma De Mallorca, Balearic Islands, Spain
Hospital Son Llatzer
🇪🇸Palma De Mallorca, Balearic Islands, Spain
Institut Català d'Oncologia - Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
University Hospital Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Clinica Universidad de Navarra -Madrid
🇪🇸Pamplona, Navarra, Spain
Clinica Universidad de Navarra - Pamplona
🇪🇸Pamplona, Navarre, Spain
Hospital Universitario de Canarias
🇪🇸Tenerife, Santa Cruz de Tenerife, Spain
Hospital Universitari Vall d'hebron
🇪🇸Barcelona, Spain
Hospital Clinic of Barcelona
🇪🇸Barcelona, Spain
Institut Català d'Oncologia - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Josep Trueta ICO Girona
🇪🇸Girona, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Complejo Asistencial Universitario de Salamanca - Hospital ClÃnico
🇪🇸Salamanca, Spain
Hospital Universitari i Politècnic la Fe
🇪🇸Valencia, Spain
Hospital Universitario 12 de Octubre
🇪🇸Vila-real, Spain
National Taiwan University Hospital
🇨🇳Taipei City, Taipei, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Ankara UMF
🇹🇷Ankara, Turkey
Gazi University
🇹🇷Ankara, Turkey
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Ege Universitesi Tip Fakultesi
🇹🇷İzmir, Turkey
University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
🇬🇧Birmingham, England, United Kingdom
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
🇬🇧High Heaton, England, United Kingdom
Barts Health NHS Trust
🇬🇧London, England, United Kingdom
University College London Hospitals
🇬🇧London, England, United Kingdom
Manchester University NHS Foundation Trust
🇬🇧Manchester, England, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, England, United Kingdom
Belfast City Hospital
🇬🇧Belfast, United Kingdom