Light Chain (AL) AmyloidosisPhase 3AFFIRM-ALNCT04973137
A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis
A Phase 3 study testing Birtamimab in people with Light Chain (AL) Amyloidosis, run by Prothena Biosciences Ltd. at 110 sites in 23 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Light Chain (AL) Amyloidosis
- What is being tested?
- Birtamimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 208 participants
- Where
- 110 sitesin 23 countries
- Study dates
- 30 Aug 2021to 20 Jun 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
- Planning to use any other investigational treatment during the study
Trial locations and contacts
110 sites in 23 countries.
110 sites in 23 countries
United States22 sites
Johns Hopkins University
Bethesda, Maryland, 20814-1422
Boston University School of Med.
Boston, Massachusetts, 02118
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195
The Ohio State University College of Medicine
Columbus, Ohio, 43210
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
Duke Clinical Research Institute
Durham, North Carolina, 27705
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
Froedtert and Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt - Ingram Cancer Center - Henry-Joyce Cancer Clinic
Nashville, Tennessee, 37232
Perlmutter Cancer Center - 38th Street
New York, New York, 10016
Columbia University Irving Medical Center
New York, New York, 10032
New York University Langone Hospital - Long Island
New York, New York, 11501
Yale Cancer Center
North Haven, Connecticut, 06473
University of Nebraska Medical Center
Omaha, Nebraska, 68105
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
University of Washington
Seattle, Washington, 98109
Smilow Cancer Hospital Care Center at Trumbull
Trumbull, Connecticut, 06611
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Cleveland Clinic Florida
Weston, Florida, 33331
France13 sites
CHU de Bordeaux
Bordeaux
Hôpitaux Universitaires Henri Mondor
Créteil, Créteil, 94000
Hopital Henri Mondor, Creteil
Créteil
Hôpital Claude Huriez
Lille, Nord, 59037
CHU Nantes
Nantes, Pays de la Loire Region, 44093
Pitie-Salpêtrière Hospital
Paris, Ill-de-France, 75013
Hopital Necker
Paris, Ill-de-France, 75743
Hôpital Necker-Enfants Malades
Paris
Hôpital Haut-Lévêque
Pessac, Gironde, 33604
Centre Hospitalier Universitaire Poitiers
Poitiers, Vienne, 86021
Hopital Rangueil
Toulouse, Midi-Pyrenees, 31059
Hôpital Bretonneau
Tours, Centre-Val de Loire, 37044
Hôpitaux de Brabois
Vandœuvre-lès-Nancy, Lorraine, 54511
Spain12 sites
Institut Català d'Oncologia - Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Clinic of Barcelona
Barcelona, Barcelona, 08036
Institut Català d'Oncologia - Hospital Duran i Reynals
Barcelona, Barcelona, 08908
Hospital Josep Trueta ICO Girona
Girona, Girona, 17007
Hospital Ramon y Cajal
Madrid, Madrid, 28034
Hospital Universitario Son Espases
Palma de Mallorca, Balearic Islands, 07120
Clinica Universidad de Navarra - Pamplona
Pamplona, Navarre, 31008
Clinica Universidad de Navarra -Madrid
Pamplona, Navarre
Complejo Asistencial Universitario de Salamanca - Hospital Clínico
Salamanca, Salamanca, 37007
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Santa Cruz de Tenerife, 38320
University Hospital Marqués de Valdecilla
Santander, Cantabria, 39008
Hospital Universitario 12 de Octubre
Vila-real, 1254
South Korea9 sites
Pusan National University Hospital
Busan, 49241
Kosin University Gospel Hospital
Busan, 602702
Keimyung University Dongsan Hospital
Daegu, Gyeongsangbuk-do, 42601
Chonnam National University Hwasun Hospital
Gwangju, Jeollanam-do, 58128
Gachon University Gil Medical Center
Incheon, 21565
Samsung Medical Center
Seoul, Seoul, 06351
Severance Hospital
Seoul, Seoul Teugbyeols, 120-752
Seoul National University Hospital
Seoul, 03080
The Catholic University of Korea - Seoul St. Mary's Hospital
Seoul, 06591
Israel6 sites
Rabin Medical Center - Beilinson Hospital
Ashkelon, Southern District, 7830604
Barzilai Medical Center
Ashkelon, 7830604
Bnai Zion Medical Center
Haifa, Haifa District, 31048
Rambam Medical Center
Haifa, Haifa District, 3109601
Carmel Medical Center
Haifa, 3436212
Hadassah Medical Center
Jerusalem, Jerusalem, 9112001
Japan6 sites
Nagoya City University Hospital
Aichi
Fukushima Medical University Hospital
Fukushima, Fukushima, 960-1247
Kyoto Kuramaguchi Medical Center
Kita, Kyoto
Shinshu University Hospital
Matsumoto, Nagano, 390-0802
Red Cross Medical Center
Shibuya-ku, Tokyo, 150-8935
Jichi medical university hospital
Shimotsuke, Tochigi
Austria4 sites
Paracelsus Medical University
Salzburg, State of Salzburg, 5020
Paracelsus Medical University
Salzburg
Medizinische Universität Wien
Vienna
Medizinische Universität
Vienna
Belgium4 sites
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
Ostend, Oostende, 8400
AZ Sint-Jan Brugge-Oostende AV
Ostend
Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
Yvoir, Yvoir, 5530
CHU UCL Namur (Site Godinne)
Yvoir
Turkey (Türkiye)4 sites
Ankara UMF
Ankara, Ankara, 06100
Gazi University
Ankara, Ankara, 06500
Istanbul University Cerrahpasa Medical Faculty
Istanbul, Istanbul, 34320
Ege Universitesi Tip Fakultesi
Izmir, İzmir, 35100
United Kingdom4 sites
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
High Heaton, England, NE77DN
Barts Health NHS Trust
London, England, EC1A7BE
University College London Hospitals
London, England, NW12PG
Manchester University NHS Foundation Trust
Manchester, England, M139WL
Germany3 sites
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Uniklinik Köln
Köln, Baden-Wurttemberg, 50937
University Medicine Mainz
Mainz, Rhineland-Palatinate, 55131
Greece3 sites
Alexandra General Hospital
Athens, Attica, 11528
University Hospital of Patras
Patra, Peloponnese, 26504
Theagenio Anti-Cancer Hospital of Thessaloniki
Thessaloniki, Central Macedonia, 54007
Taiwan3 sites
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, Kaohsiung, 833
Taipei Veterans General Hospital
Taipei, Taipei, 11217
National Taiwan University Hospital
Taipei City, Taipei, 10047
Australia2 sites
SESLHD: St George Hospital
Kogarah, New South Wales, 2217
Royal Perth Hospital
Perth, Western Australia, 6000
Canada2 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N4N2
Royal Victoria Hospital
Montreal, Quebec, H3A1A1
Czechia2 sites
Fakultni nemocnice ostrava
Ostrava-Poruba, Moravian-Silesian, 70852
Všeobecná fakultní nemocnice v Praze
Prague, Prague, 12808
Ireland2 sites
Cork University Hospital
Cork, Munster, T12 DFK4
Cancer Clinical Trials and Research Unit, Beaumont Hospital
Dublin
Italy2 sites
Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
Bologna, Bologna, 40138
Azienda Ospedaliero-Universitaria Pisana
Pisa, 56124
Netherlands2 sites
Universitair Medisch Centrum Groningen
Groningen, Provincie Groningen, 9713GZ
Maastricht Universitair Medisch Centrum
Maastricht, Limburg, 6229HX
Portugal2 sites
Hospital de Braga
Braga, Braga District, 4710-243
Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria
Lisbon, Lisbon District, 1649-028
Hungary1 site
Semmelweis Egyetem - I. sz. Belgyógyászati Klinika
Budapest, Budapest, 1087
Poland1 site
Klinika Hematologii i Transplantologii
Gdansk, Pomeranian Voivodeship, 80-214
About this study
Official title: 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.
Read the 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.
- Conditions
- Light Chain (AL) Amyloidosis
- Being tested
- Birtamimab, Placebo, Standard of Care Chemotherapy
- Keywords
- Light Chain (AL) Amyloidosis, Mayo Stage IV, birtamimab
- Medical subject headings
- Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BirtamimabDrug
Intravenous administration of 24 mg/kg birtamimab every 28 days
PlaceboOther
Intravenous 0.9% Saline administration as a placebo every 28 days
Standard of Care ChemotherapyDrug
Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo; Drug: Standard of Care Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to All-cause Mortality for the Double Blind Phase
Comparison of time to all-cause mortality for birtamimab and placebo control.
Measured: 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
Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance calculated as the value at 9 months minus the value at baseline.
Measured: Month 9
Physical Component Summary Score of the Short Form-36, Version 2 at Month 9
Change from baseline to Month 9 in the Short Form-36, version 2 (SF-36) calculated as the value at 9 months minus the value at baseline.
SF-36 v2 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.
Measured: Month 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2021
- Study start30 Aug 2021
- Primary completion2 Apr 2025
- Study completion20 Jun 2025
Why it stopped: The AFFIRM-AL clinical trial did not meet its primary endpoint.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Light Chain (AL) AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prothena Biosciences Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04973137
- Sponsor's protocol ID
- NEOD001-301
- Acronym
- AFFIRM-AL
- Status last verified
- Jul 2025
- First submitted
- 1 Jul 2021
- Last updated
- 16 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Palladini G, Liedtke M, Zago W, Dolan P, Kinney GG, Gertz MA. The mechanism of action, pharmacological characteristics, and clinical utility of the amyloid depleter birtamimab for the potential treatment of AL amyloidosis. Leuk Lymphoma. 2024 Aug;65(8):1068-1078. doi: 10.1080/10428194.2024.2337803. Epub 2024 Apr 11.
PubMed 38600883Gertz 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.
PubMed 37366170