A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients with AL Amyloidosis

Phase 3

Recruiting

• Conditions: Light Chain (AL) Amyloidosis
• Interventions: Other: Placebo; Drug: Birtamimab; Drug: Standard of Care Chemotherapy

• 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.

Study Timeline

• Study First Submitted: 2021-07-01
• Study First Submitted QC: 2021-07-21
• Study First Posted: 2021-07-22
• Study Start: 2021-08-30
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-30
• Last Update Posted: 2024-11-01
• Primary Completion: 2025-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

Not provided

Exclusion Criteria

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

Fakultní Nemocnice Brno; 🇨🇿 Brno, Jihormoravsky Kraj, Czechia

Fakultni nemocnice ostrava; 🇨🇿 Ostrava-Poruba, Moravian-Silesian, Czechia

Všeobecná fakultní 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; 🇬🇷 Thessaloníki, Central Macedonia, Greece

University Hospital of Patras; 🇬🇷 Patra, Peloponnese, Greece

Pécsi Tudományegyetem Klinikai Központ; 🇭🇺 Pécs, Baranya, Hungary

Szent-Györgyi Albert Klinikai Központ; 🇭🇺 Szeged, Csongrad, Hungary

Debreceni Egyetem Klinikai Központ; 🇭🇺 Debrecen, Hajdu-Bihar County, Hungary

Semmelweis Egyetem - I. sz. Belgyógyászati Klinika; 🇭🇺 Budapest, Hungary

Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet; 🇭🇺 Budapest, 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 Clínico; 🇪🇸 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