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

NCT04973137 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: NEOD001-301
• Study Type: interventional
• Target: 208
• Locations: 22 countries
• Sites: 108

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.

Conditions

Light Chain (AL) Amyloidosis

Keywords

Light Chain (AL) Amyloidosis; Mayo Stage IV; birtamimab

Outcome Measures

Primary Outcomes (1)

• 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, assessed up to 39 months.

Secondary Outcomes (2)

• 6MWT Distance at Month 9

  Month 9

• Physical Component Summary Score of the Short Form-36, Version 2 at Month 9

  Month 9

Study Arms (2)

Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of study

EXPERIMENTAL

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.

Drug: Birtamimab; Drug: Standard of Care Chemotherapy

Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of study

PLACEBO COMPARATOR

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.

Other: Placebo; Drug: Standard of Care Chemotherapy

Interventions

Birtamimab DRUG

Intravenous administration of 24 mg/kg birtamimab every 28 days

Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of study

Placebo OTHER

Intravenous 0.9% Saline administration as a placebo every 28 days

Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of study

Standard of Care Chemotherapy DRUG

Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care

Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of study; Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Prothena Biosciences Ltd.: lead

Study Sites (110)

Yale Cancer Center

North Haven, Connecticut, 06473, United States

Location

Smilow Cancer Hospital Care Center at Trumbull

Trumbull, Connecticut, 06611, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Johns Hopkins University

Bethesda, Maryland, 20814-1422, United States

Location

Boston University School of Med.

Boston, Massachusetts, 02118, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68105, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Perlmutter Cancer Center - 38th Street

New York, New York, 10016, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

New York University Langone Hospital - Long Island

New York, New York, 11501, United States

Location

Duke Clinical Research Institute

Durham, North Carolina, 27705, United States

Location

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

Location

The Ohio State University College of Medicine

Columbus, Ohio, 43210, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt - Ingram Cancer Center - Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Froedtert and Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

SESLHD: St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Paracelsus Medical University

Salzburg, Salzburg, 5020, Austria

Location

Paracelsus Medical University

Salzburg, Austria

Location

Medizinische Universität Wien

Vienna, Austria

Location

Medizinische Universität

Vienna, Austria

Location

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan

Ostend, Oostende, 8400, Belgium

Location

Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne

Yvoir, Yvoir, 5530, Belgium

Location

AZ Sint-Jan Brugge-Oostende AV

Ostend, Belgium

Location

CHU UCL Namur (Site Godinne)

Yvoir, Belgium

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N4N2, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, H3A1A1, Canada

Location

Fakultni nemocnice ostrava

Ostrava-Poruba, Moravian-Silesian, 70852, Czechia

Location

Všeobecná fakultní nemocnice v Praze

Prague, Prague, 12808, Czechia

Location

Odense Universitetshospital

Odense, Region Syddanmark, 5000, Denmark

Location

Hôpital Bretonneau

Tours, Centre-Val de Loire, 37044, France

Location

Hôpitaux Universitaires Henri Mondor

Créteil, Créteil, 94000, France

Location

Hôpital Haut-Lévêque

Pessac, Gironde, 33604, France

Location

Pitie-Salpêtrière Hospital

Paris, Ill-de-France, 75013, France

Location

Hopital Necker

Paris, Ill-de-France, 75743, France

Location

Hôpitaux de Brabois

Vandœuvre-lès-Nancy, Lorraine, 54511, France

Location

Hopital Rangueil

Toulouse, Midi-Pyrenees, 31059, France

Location

Hôpital Claude Huriez

Lille, Nord, 59037, France

Location

CHU Nantes

Nantes, Pays de la Loire Region, 44093, France

Location

Centre Hospitalier Universitaire Poitiers

Poitiers, Vienne, 86021, France

Location

CHU de Bordeaux

Bordeaux, France

Location

Hopital Henri Mondor, Creteil

Créteil, France

Location

Hôpital Necker-Enfants Malades

Paris, France

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Uniklinik Köln

Köln, Baden-Wurttemberg, 50937, Germany

Location

University Medicine Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Alexandra General Hospital

Athens, Attica, 11528, Greece

Location

Theagenio Anti-Cancer Hospital of Thessaloniki

Thessaloniki, Central Macedonia, 54007, Greece

Location

University Hospital of Patras

Patra, Peloponnese, 26504, Greece

Location

Semmelweis Egyetem - I. sz. Belgyógyászati Klinika

Budapest, Budapest, 1087, Hungary

Location

Cork University Hospital

Cork, Munster, T12 DFK4, Ireland

Location

Cancer Clinical Trials and Research Unit, Beaumont Hospital

Dublin, Ireland

Location

Bnai Zion Medical Center

Haifa, Haifa District, 31048, Israel

Location

Rambam Medical Center

Haifa, Haifa District, 3109601, Israel

Location

Hadassah Medical Center

Jerusalem, Jerusalem, 9112001, Israel

Location

Rabin Medical Center - Beilinson Hospital

Ashkelon, Southern District, 7830604, Israel

Location

Barzilai Medical Center

Ashkelon, 7830604, Israel

Location

Carmel Medical Center

Haifa, 3436212, Israel

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi

Bologna, Bologna, 40138, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, 56124, Italy

Location

Fukushima Medical University Hospital

Fukushima, Fukushima, 960-1247, Japan

Location

Kyoto Kuramaguchi Medical Center

Kita, Kyoto, Japan

Location

Shinshu University Hospital

Matsumoto, Nagano, 390-0802, Japan

Location

Jichi medical university hospital

Shimotsuke, Tochigi, Japan

Location

Red Cross Medical Center

Shibuya-ku, Tokyo, 150-8935, Japan

Location

Nagoya City University Hospital

Aichi, Japan

Location

Maastricht Universitair Medisch Centrum

Maastricht, Limburg, 6229HX, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, Provincie Groningen, 9713GZ, Netherlands

Location

Klinika Hematologii i Transplantologii

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Hospital de Braga

Braga, Braga District, 4710-243, Portugal

Location

Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria

Lisbon, Lisbon District, 1649-028, Portugal

Location

Keimyung University Dongsan Hospital

Daegu, Gyeongsangbuk-do, 42601, South Korea

Location

Chonnam National University Hwasun Hospital

Gwangju, Jeollanam-do, 58128, South Korea

Location

Samsung Medical Center

Seoul, Seoul, 06351, South Korea

Location

Severance Hospital

Seoul, Seoul Teugbyeols, 120-752, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Kosin University Gospel Hospital

Busan, 602702, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

The Catholic University of Korea - Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Institut Català d'Oncologia - Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Clinic of Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Institut Català d'Oncologia - Hospital Duran i Reynals

Barcelona, Barcelona, 08908, Spain

Location

University Hospital Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Josep Trueta ICO Girona

Girona, Girona, 17007, Spain

Location

Hospital Ramon y Cajal

Madrid, Madrid, 28034, Spain

Location

Clinica Universidad de Navarra - Pamplona

Pamplona, Navarre, 31008, Spain

Location

Clinica Universidad de Navarra -Madrid

Pamplona, Navarre, Spain

Location

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, Salamanca, 37007, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Santa Cruz de Tenerife, 38320, Spain

Location

Hospital Universitario 12 de Octubre

Vila-real, 1254, Spain

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Kaohsiung, 833, Taiwan

Location

National Taiwan University Hospital

Taipei City, Taipei, 10047, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taipei, 11217, Taiwan

Location

Ankara UMF

Ankara, Ankara, 06100, Turkey (Türkiye)

Location

Gazi University

Ankara, Ankara, 06500, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, Istanbul, 34320, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Izmir, İzmir, 35100, Turkey (Türkiye)

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

High Heaton, England, NE77DN, United Kingdom

Location

Barts Health NHS Trust

London, England, EC1A7BE, United Kingdom

Location

University College London Hospitals

London, England, NW12PG, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, England, M139WL, United Kingdom

Location

Related Publications (1)

• Gertz MA, Cohen AD, Comenzo RL, Kastritis E, Landau HJ, Libby EN, Liedtke M, Sanchorawala V, Schonland S, Wechalekar A, Zonder JA, Palladini G, Walling J, Guthrie S, Nie C, Karp C, Jin Y, Kinney GG, Merlini G. Birtamimab plus standard of care in light-chain amyloidosis: the phase 3 randomized placebo-controlled VITAL trial. Blood. 2023 Oct 5;142(14):1208-1218. doi: 10.1182/blood.2022019406.

  PMID: 37366170 DERIVED

MeSH Terms

Conditions

Amyloidosis

Interventions

birtamimab

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Katelyn Diffin
• Organization: Prothena Biosciences Limited

AFFIRM-ALClinicalTrials@prothena.com

650-837-8550

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: July 22, 2021
• Study Start: August 30, 2021
• Primary Completion: April 2, 2025
• Study Completion: June 20, 2025
• Last Updated: December 16, 2025
• Results First Posted: December 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); US (22); CZ (2); CA (2); HU (1); DK (1); BE (4); JP (6); PT (2); KR (9); TW (3); GB (4); DE (3); AU (4); IT (2); GR (3); TU (4); IE (2); IL (6); NL (2); ES (12); FR (13)