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Evaluating birtamimab for patients with advanced AL amyloidosis

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

Phase 3 Interventional Prothena Biosciences Ltd. · NCT04973137

This study is testing a new treatment called birtamimab for people with advanced AL amyloidosis to see if it helps them live longer when combined with standard chemotherapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment220 (estimated)
Ages18 Years and up
SexAll
SponsorProthena Biosciences Ltd. Industry-sponsored
Drugs / interventionsbirtamimab, daratumumab, chemotherapy
Locations144 sites (San Francisco, California and 143 other locations)
Trial IDNCT04973137 on ClinicalTrials.gov

What this trial studies

This Phase 3 multicenter, global, randomized, double-blind, placebo-controlled study aims to assess the efficacy and safety of birtamimab in patients diagnosed with Mayo Stage IV AL amyloidosis. Approximately 220 newly diagnosed patients will be enrolled and randomized to receive either birtamimab or a placebo alongside standard chemotherapy. The primary objective is to evaluate the time to all-cause mortality during the double-blind phase, followed by an optional open-label extension phase where all participants will receive birtamimab. This study seeks to provide insights into the long-term safety and efficacy of birtamimab in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed, treatment-naïve Mayo Stage IV AL amyloidosis and cardiac involvement.

Not a fit: Patients with AL amyloidosis who are not in Mayo Stage IV or have previously received treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates for patients with advanced AL amyloidosis.

How similar studies have performed: Previous studies have shown promise in treating AL amyloidosis, but the specific approach with birtamimab is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

San Francisco, California and 143 other locations

+94 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Light Chain AmyloidosisMayo Stage IVbirtamimab
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.