A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis (AFFIRM-AL)

A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of Care in Mayo Stage IV Subjects With Light Chain (AL) Amyloidosis

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.

Study Overview

• Status: Recruiting
• Conditions: Light Chain (AL) Amyloidosis
• Intervention / Treatment: Drug: Birtamimab; Drug: Standard of Care Chemotherapy; Other: Placebo

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 150 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 Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Christie Nie; Phone Number: 650-837-8550; Email: AFFIRM-ALClinicalTrial@prothena.com
• Study Contact Backup: Name: Sonia Romero; Phone Number: 650-837-8550; Email: AFFIRM-ALClinicalTrial@prothena.com

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • SESLHD: St George Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Withdrawn
      • Icon Cancer Centre - Wesley
    • South Brisbane, Queensland, Australia, 4101
      • Withdrawn
      • Icon Cancer Center
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Recruiting
      • Box Hill Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Recruiting
      • Royal Perth Hospital
• Austria
  • Salzburg, Austria
    • Recruiting
    • Paracelsus Medical University
  • Salzburg, Austria, 5020
    • Recruiting
    • Paracelsus Medical University
  • Vienna, Austria
    • Recruiting
    • Medizinische Universität
  • Wien, Austria
    • Recruiting
    • Medizinische Universität Wien
    • Contact: Hermine Agis, MD
    • Principal Investigator: Hermine Agis
• Belgium
  • Oostende, Belgium
    • Recruiting
    • AZ Sint-Jan Brugge-Oostende AV
  • Oostende, Belgium, 8400
    • Recruiting
    • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
  • Yvoir, Belgium
    • Recruiting
    • CHU UCL Namur (Site Godinne)
  • Yvoir, Belgium, 5530
    • Recruiting
    • Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N2
      • Recruiting
      • Tom Baker Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H3A1A1
      • Recruiting
      • Royal Victoria Hospital
• Czechia
  • Jihormoravsky Kraj
    • Brno, Jihormoravsky Kraj, Czechia, 62500
      • Recruiting
      • Fakultni nemocnice Brno
  • Moravian-Silesian
    • Ostrava-Poruba, Moravian-Silesian, Czechia, 70852
      • Recruiting
      • Fakultni nemocnice Ostrava
  • Prague
    • Praha, Prague, Czechia, 12808
      • Recruiting
      • Vseobecna fakultni nemocnice v Praze
• Denmark
  • Syddanmark
    • Odense, Syddanmark, Denmark, 5000
      • Recruiting
      • Odense Universitetshospital
• France
  • Bordeaux, France
    • Recruiting
    • CHU de Bordeaux
  • Créteil, France, 94000
    • Recruiting
    • Hopitaux Universitaires Henri Mondor
  • Créteil, France
    • Recruiting
    • Hopital Henri Mondor, Creteil
  • Limoges, France, 87000
    • Recruiting
    • Centre Hospitalier Universitaire Limoges
  • Paris, France
    • Recruiting
    • Hôpital Necker-Enfants Malades
  • Centre
    • Tours Cedex 9, Centre, France, 37044
      • Recruiting
      • Hôpital Bretonneau
  • Gironde
    • Pessac, Gironde, France, 33604
      • Recruiting
      • Hôpital Haut-Lévêque
  • Ill-de-France
    • Paris, Ill-de-France, France, 75013
      • Recruiting
      • Pitié-Salpêtrière Hospital
    • Paris Cedex 15, Ill-de-France, France, 75743
      • Recruiting
      • Hôpital Necker
  • Lorraine
    • Vandœuvre-lès-Nancy, Lorraine, France, 54511
      • Recruiting
      • Hopitaux de Brabois
  • Midi-Pyrenees
    • Toulouse Cedex 9, Midi-Pyrenees, France, 31059
      • Recruiting
      • Hôpital Rangueil
  • Nord
    • Lille, Nord, France, 59037
      • Recruiting
      • Hopital Claude Huriez
  • Pays De La Loire
    • Nantes, Pays De La Loire, France, 44093
      • Recruiting
      • Chu Nantes
  • Vienne
    • Poitiers, Vienne, France, 86021
      • Recruiting
      • Centre Hospitalier Universitaire Poitiers
• Germany
  • Berlin, Germany, 10117
    • Withdrawn
    • Charité Campus Mitte
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69120
      • Recruiting
      • Universitätsklinikum Heidelberg
  • Baden-Württemberg
    • Köln, Baden-Württemberg, Germany, 50937
      • Recruiting
      • Uniklinik Köln
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Recruiting
      • University Medicine Mainz
• Greece
  • Attica
    • Athens, Attica, Greece, 11528
      • Recruiting
      • Alexandra General Hospital
  • Central Macedonia
    • Thessaloníki, Central Macedonia, Greece, 54007
      • Recruiting
      • Theagenio Anti-Cancer Hospital of Thessaloniki
  • Peloponnese
    • Patra, Peloponnese, Greece, 26504
      • Recruiting
      • University Hospital of Patras
• Hungary
  • Budapest, Hungary, 1087
    • Recruiting
    • Semmelweis Egyetem - I. sz. Belgyógyászati Klinika
  • Budapest, Hungary, 1097
    • Recruiting
    • Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
  • Baranya
    • Pécs, Baranya, Hungary, 7622
      • Withdrawn
      • Pécsi Tudományegyetem Klinikai Központ
  • Csongrad
    • Szeged, Csongrad, Hungary, 6725
      • Withdrawn
      • Szent-Gyorgyi Albert Klinikai Kozpont
  • Hajdu-Bihar County
    • Debrecen, Hajdu-Bihar County, Hungary, 4032
      • Withdrawn
      • Debreceni Egyetem Klinikai Kozpont
• Ireland
  • Dublin, Ireland
    • Recruiting
    • Cancer Clinical Trials and Research Unit, Beaumont Hospital
  • Dublin, Ireland
    • Recruiting
    • Beaumont Hospital - Dublin
  • Munster
    • Cork, Munster, Ireland, T12 DFK4
      • Not yet recruiting
      • Cork University Hospital
• Israel
  • Ashdod, Israel, 7747629
    • Recruiting
    • Samson Assuta Ashdod Hospital
  • Ashkelon, Israel, 7830604
    • Recruiting
    • Barzilai Medical Center
  • Haifa, Israel, 3436212
    • Recruiting
    • Carmel Medical Center
  • Haifa District
    • Haifa, Haifa District, Israel, 31048
      • Recruiting
      • Bnai Zion Medical Center
    • Haifa, Haifa District, Israel, 3109601
      • Recruiting
      • Rambam Medical Center
  • Jerusalem District
    • Jerusalem, Jerusalem District, Israel, 9112001
      • Recruiting
      • Hadassah Medical Center
  • Southern District
    • Ashkelon, Southern District, Israel, 7830604
      • Recruiting
      • Rabin Medical Center - Beilinson Hospital
• Italy
  • Ancona, Italy, 60020
    • Recruiting
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
  • Bologna, Italy, 40138
    • Recruiting
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
  • Brescia, Italy, 25123
    • Recruiting
    • ASST Spedali Civili
  • Catania, Italy, 95125
    • Recruiting
    • Azienda Ospedaliero Universitaria Policlinico Gaspare Rodolico - San Marco
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo
  • Pisa, Italy, 56124
    • Recruiting
    • Azienda Ospedaliero-Universitaria Pisana
  • Roma, Italy, 00161
    • Recruiting
    • Umberto I - Policlinico di Roma
• Japan
  • Aichi, Japan
    • Recruiting
    • Nagoya City University Hospital
  • Fukushima, Japan, 960-1247
    • Recruiting
    • Fukushima Medical University Hospital
  • Kyoto
    • Kita, Kyoto, Japan
      • Recruiting
      • Kyoto Kuramaguchi Medical Center
  • Nagano
    • Matsumoto, Nagano, Japan, 390-0802
      • Recruiting
      • Shinshu University Hospital
  • Tochigi
    • Shimotsuke, Tochigi, Japan
      • Recruiting
      • Jichi Medical University Hospital
  • Tokushima
    • Kuramoto, Tokushima, Japan
      • Recruiting
      • Tokushima University Hospital
  • Tokyo
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Recruiting
      • Red Cross Medical Center
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Recruiting
    • Pusan National University Hospital
  • Busan, Korea, Republic of, 602702
    • Recruiting
    • Kosin University Gospel Hospital
  • Incheon, Korea, Republic of, 21565
    • Recruiting
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 04763
    • Recruiting
    • Hanyang University Seoul Hospital
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • The Catholic University of Korea - Seoul St. Mary's Hospital
  • Gyeongsangbugdo
    • Daegu, Gyeongsangbugdo, Korea, Republic of, 42601
      • Recruiting
      • Keimyung University Dongsan Hospital
  • Jeollanam-do
    • Gwangju, Jeollanam-do, Korea, Republic of, 58128
      • Recruiting
      • Chonnam National University Hwasun Hospital
  • Seoul Teugbyeols
    • Seoul, Seoul Teugbyeols, Korea, Republic of, 120-752
      • Recruiting
      • Severance Hospital
• Netherlands
  • Groningen, Netherlands, 9713GZ
    • Withdrawn
    • Universitair Medisch Centrum Groningen
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229HX
      • Recruiting
      • Maastricht Universitair Medisch Centrum
• Poland
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-214
      • Recruiting
      • Klinika Hematologii i Transplantologii
• Portugal
  • Braga, Portugal, 4710-243
    • Recruiting
    • Hospital de Braga
  • Coimbra, Portugal, 3000-075
    • Recruiting
    • Centro Hospitalar e Universitário de Coimbra
  • Lisboa, Portugal, 1649-028
    • Recruiting
    • Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic of Barcelona
  • Barcelona, Spain, 08908
    • Recruiting
    • Institut Catalá d'Oncología - Hospital Duran i Reynals
  • Girona, Spain, 17007
    • Recruiting
    • Hospital Josep Trueta ICO Girona
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Ramón y Cajal
  • Salamanca, Spain, 37007
    • Recruiting
    • Complejo Asistencial Universitario de Salamanca - Hospital Clinico
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politecnic La Fe
  • Vila-real, Spain, 1254
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Balearic Islands
    • Palma De Mallorca, Balearic Islands, Spain, 07120
      • Recruiting
      • Hospital Universitario Son Espases
    • Palma De Mallorca, Balearic Islands, Spain, 07198
      • Recruiting
      • Hospital Son Llatzer
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • Institut Català d'Oncologia - Hospital Germans Trias i Pujol
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • University Hospital Marqués de Valdecilla
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • Hospital Universitario Puerta de Hierro - Majadahonda
  • Navarra
    • Pamplona, Navarra, Spain
      • Recruiting
      • Clinica Universidad de Navarra -Madrid
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra - Pamplona
  • Santa Cruz De Tenerife
    • Tenerife, Santa Cruz De Tenerife, Spain, 38320
      • Recruiting
      • Hospital Universitario de Canarias
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei
    • Taipei City, Taipei, Taiwan, 10047
      • Recruiting
      • National Taiwan University Hospital
• Turkey
  • Ankara, Turkey, 06100
    • Recruiting
    • Ankara UMF
  • Ankara, Turkey, 06500
    • Recruiting
    • Gazi University
  • Istanbul, Turkey, 34320
    • Not yet recruiting
    • Istanbul University Cerrahpasa Medical Faculty
  • İzmir, Turkey, 35100
    • Recruiting
    • Ege Üniversitesi Tip Fakültesi
• United Kingdom
  • Belfast, United Kingdom
    • Recruiting
    • Belfast City Hospital
  • England
    • Birmingham, England, United Kingdom, B152SY
      • Recruiting
      • University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
    • High Heaton, England, United Kingdom, NE77DN
      • Recruiting
      • The Newcastle upon Tyne Hospitals NHS Foundation Trust
    • London, England, United Kingdom, EC1A7BE
      • Recruiting
      • Barts Health NHS Trust
    • London, England, United Kingdom, NW12PG
      • Recruiting
      • Univiersity College London Hospitals
    • Manchester, England, United Kingdom, M139WL
      • Recruiting
      • Manchester University NHS Foundation Trust
    • Nottingham, England, United Kingdom, NG51PB
      • Withdrawn
      • Nottingham University Hospitals NHS Trust
• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Recruiting
      • St. Francis Hospital
    • North Haven, Connecticut, United States, 06473
      • Recruiting
      • Yale Cancer Center
    • Trumbull, Connecticut, United States, 06611
      • Recruiting
      • Smilow Cancer Hospital Care Center at Trumbull
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • MedStar Georgetown University Hospital
  • Florida
    • Weston, Florida, United States, 33331
      • Recruiting
      • Cleveland Clinic Florida
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Recruiting
      • Goshen Center for Cancer Care
  • Maryland
    • Bethesda, Maryland, United States, 20814-1422
      • Recruiting
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston University School of Med.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Withdrawn
      • University of Michigan Rogel Cancer Center
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Barbara Ann Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic - Rochester
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68105
      • Recruiting
      • University of Nebraska Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10016
      • Recruiting
      • Perlmutter Cancer Center - 38th Street
    • New York, New York, United States, 11501
      • Not yet recruiting
      • New York University Langone Hospital - Long Island
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke Clinical Research Institute
    • Winston-Salem, North Carolina, United States, 27157
      • Withdrawn
      • Wake Forest Baptist Health - Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Main Campus
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University College of Medicine
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • University of Tennessee Medical Center
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt - Ingram Cancer Center - Henry-Joyce Cancer Clinic
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor University Medical Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert and Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria for Double-blind Phase:

• Aged ≥18 years and legal age of consent according to local regulations
• Newly diagnosed and AL amyloidosis treatment-naïve with cardiac involvement
• Confirmed diagnosis of AL amyloidosis
• Confirmed Mayo Stage IV AL Amyloidosis as defined by NT-proBNP ≥1800 pg/mL and Troponin-T ≥0.025 ng/mL or high sensitivity cardiac troponin T≥40ng/L and dFLC ≥18 mg/dL
• Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly

Inclusion Criteria for Open-label (OLE) Phase:

• Must not have discontinued treatment in Double-blind Phase
• WOCBP must have a negative pregnancy test and must agree to use highly effective contraception through 90 days following last study drug administration
• Male subjects must be surgically sterile or agree to use highly effective contraception through 90 days following last study drug administration
• Ability to understand and willingness to sign an ICF prior to initiating the OLE Phase

Key Exclusion Criteria for Double-blind Phase:

• Non-AL amyloidosis
• NT-proBNP >8500 pg/mL
• Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma except for malignancy biomarker of involved/uninvolved serum free light chain ratio ≥100
• Subject is eligible for and plans to undergo ASCT or organ transplant during the study
• Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit
• Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease
• ECG evidence of acute ischemia or active conduction system abnormalities
• Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1
• Prior radiotherapy within 4 weeks of Month 1-Day 1
• Prior treatment with plasma cell-directed chemotherapy, birtamimab, daratumumab, 11- 1F4, anti-serum amyloid P antibody, doxycycline for amyloid, or other investigational treatment directed at amyloid
• Waldenström's macroglobulinemia and/or immunoglobulin M monoclonal gammopathy

Exclusion Criteria for OLE Phase:

• Any medical condition or clinically significant abnormality on physical, neurological, laboratory, vital signs, or ECG examination that precludes treatment with birtamimab or participation in the study, in the medical judgment of the Investigator
• Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would interfere with subject's ability to safely receive treatment or complete study assessments
• History of Grade ≥3 infusion-related AEs during the Double-blind Phase or hypersensitivity to birtamimab
• Unable or unwilling to adhere to the study-specified procedures and restrictions
• Planning to use any other investigational treatment during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of study; 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. Initiation of daratumumab at randomization allowed at the discretion of the investigator for Double-blind Phase	Drug: 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
Placebo Comparator: Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of study; 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.	Drug: Standard of Care Chemotherapy; Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care; Other: Placebo; Intravenous 0.9% Saline administration as a placebo every 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to all-cause mortality for the Double Blind Phase	Comparison of time to all-cause mortality for birtamimab and placebo control.	Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6MWT distance for the Double Blind Phase	Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance	Month 9
Physical Component Summary score of the Short Form-36, version 2 for the Double Blind Phase	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.	Month 9

Collaborators and Investigators

• Sponsor: Prothena Biosciences Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 21, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Light Chain (AL) Amyloidosis; Mayo Stage IV; birtamimab
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: NEOD001-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No