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

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