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

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. The primary objective 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.

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.

Key Inclusion Criteria:

• 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 >0.03 ng/mL and dFLC ≥18 mg/dL
• Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly.

Key Exclusion Criteria:

• Non-AL amyloidosis.
• NT-proBNP >8500 pg/mL.
• Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma
• 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