AzTrials
AzTrials

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.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Other trials in United States

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

Other trials in France

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

Other trials in Spain

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

Other trials in South Korea

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

Other trials in Israel

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

Other trials in Japan

Austria4 sites

  • Paracelsus Medical University

    Salzburg, State of Salzburg, 5020

  • Paracelsus Medical University

    Salzburg

  • Medizinische Universität Wien

    Vienna

  • Medizinische Universität

    Vienna

Other trials in Austria

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

Other trials in Belgium

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

Other trials in Turkey (Türkiye)

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

Other trials in United Kingdom

Germany3 sites

  • Universitätsklinikum Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

  • Uniklinik Köln

    Köln, Baden-Wurttemberg, 50937

  • University Medicine Mainz

    Mainz, Rhineland-Palatinate, 55131

Other trials in Germany

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

Other trials in Greece

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

Other trials in Taiwan

Australia2 sites

  • SESLHD: St George Hospital

    Kogarah, New South Wales, 2217

  • Royal Perth Hospital

    Perth, Western Australia, 6000

Other trials in Australia

Canada2 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N4N2

  • Royal Victoria Hospital

    Montreal, Quebec, H3A1A1

Other trials in Canada

Czechia2 sites

  • Fakultni nemocnice ostrava

    Ostrava-Poruba, Moravian-Silesian, 70852

  • Všeobecná fakultní nemocnice v Praze

    Prague, Prague, 12808

Other trials in Czechia

Ireland2 sites

  • Cork University Hospital

    Cork, Munster, T12 DFK4

  • Cancer Clinical Trials and Research Unit, Beaumont Hospital

    Dublin

Other trials in Ireland

Italy2 sites

  • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi

    Bologna, Bologna, 40138

  • Azienda Ospedaliero-Universitaria Pisana

    Pisa, 56124

Other trials in Italy

Netherlands2 sites

  • Universitair Medisch Centrum Groningen

    Groningen, Provincie Groningen, 9713GZ

  • Maastricht Universitair Medisch Centrum

    Maastricht, Limburg, 6229HX

Other trials in Netherlands

Portugal2 sites

  • Hospital de Braga

    Braga, Braga District, 4710-243

  • Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria

    Lisbon, Lisbon District, 1649-028

Other trials in Portugal

Denmark1 site

  • Odense Universitetshospital

    Odense, Region Syddanmark, 5000

Other trials in Denmark

Hungary1 site

  • Semmelweis Egyetem - I. sz. Belgyógyászati Klinika

    Budapest, Budapest, 1087

Other trials in Hungary

Poland1 site

  • Klinika Hematologii i Transplantologii

    Gdansk, Pomeranian Voivodeship, 80-214

Other trials in Poland

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.

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 groups in NCT04973137
Study groupRoleWhat they receive
Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of studyExperimentalIntravenous 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 studyPlacebo comparatorIntravenous 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.

  1. 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)

  1. 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

  2. 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.

  1. First posted22 Jul 2021
  2. Study start30 Aug 2021
  3. Primary completion2 Apr 2025
  4. Study completion20 Jun 2025

Why it stopped: The AFFIRM-AL clinical trial did not meet its primary endpoint.

Resources

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)
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
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 38600883

  • 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.

    PubMed 37366170

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Birtamimab in people with Light Chain (AL) Amyloidosis, run by Prothena Biosciences Ltd. at 110 sites in 23 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 110 sites in United States, France, Spain, South Korea, Israel and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to All-cause Mortality for the Double Blind Phase (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04973137, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in