A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis
Purpose
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.
Condition
- Light Chain (AL) Amyloidosis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 ≥0.025 ng/mL or high sensitivity cardiac troponin T≥40ng/L and dFLC ≥18 mg/dL - Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly.
Exclusion Criteria
- 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Birtamimab plus Standard of Care Chemotherapy |
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. Initiation of daratumumab at randomization allowed at the discretion of the investigator |
|
|
Placebo Comparator Placebo plus Standard of Care Chemotherapy |
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 |
|
Recruiting Locations
Boston University School of Med.
Boston, Massachusetts 02118
Boston, Massachusetts 02118
More Details
- Status
- Recruiting
- Sponsor
- Prothena Biosciences Ltd.
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. 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.