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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 (AFFIRM-AL)

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

Nie Christie

Prothena Biosciences Limited

77 Sir John Rogerson's Quay, Block C Grand Canal Docklands, Dublin 2 D02 T804, Ireland

AFFIRM-ALClinicalTrial@prothena.com

contact trial Clinical

ICON Clinical Research GK

Kyutaromachi 4-chome 1-3, Chuo-ku, Osaka city, Osaka 541-0056, Japan

+81-6-4560-2001

ICONCR-Chiken@iconplc.com

Recruiting

June. 20, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

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 naive 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 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
- Women of childbearing potential 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 cm^2) 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 .
- Waldenstrom'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

Both

Light Chain (AL) Amyloidosis

- Birtamimab group:
Intravenous administration of 24 mg/kg birtamimab every 28 days. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care is co-administered as Standard of Care Chemotherapy
- Placebo group:
Intravenous 0.9% Saline administration as a placebo every 28 days. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care is co-administered as Standard of Care Chemotherapy

Time to all-cause mortality for the Double-blind Phase

- 6MWT distance for the Double Blind Phase
- Physical Component Summary score of the Short Form-36, version 2 for the Double Blind Phase

+81-263-35-4600

Feb. 21, 2022

No

Australia/Austria/Belgium/Canada/Czechia/Denmark/France/Germany/Greece/Hungary/Ireland/Israel/Italy/Republic of Korea/Netherlands/Poland/Portugal/Spain/Taiwan/Turkey/United Kingdom/United States