A Global Phase 3 Double-Blind, Placebo-Controlled study to assess Efficacy and Safety of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of Care in Mayo Stage IV Subjects with Light Chain (AL) Amyloidosis

Phase 1

Conditions: AL amyloidosis involves a hematologic disorder caused by clonal plasma cells that produce misfolded immunoglobulin light chains. Overproduction of misfolded light chains results in both soluble, aggregated forms of light chains and insoluble, fibrillar deposits of abnormal AL protein (amyloid), in the tissues and organs. This can cause a range of symptoms and organ dysfunction including cardiac, renal, and hepatic dysfunction, gastrointestinal involvement and neuropathy and macroglossia
MedDRA version: 20.0Level: PTClassification code 10036673Term: Primary amyloidosisSystem Organ Class: 10021428 - Immune system disorders
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2021-000037-14-AT

Lead Sponsor: Prothena Biosciences Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 220

Inclusion Criteria

1.Aged =18 years and legal age of consent according to local regulations
2.Newly diagnosed and AL amyloidosis treatment naive with cardiac involvement
3.Confirmed diagnosis of AL amyloidosis
4.Confirmed Mayo Stage IV AL Amyloidosis as defined by NT-proBNP =1800 pg/mL and Troponin-T =0.025 ng/mL (mcg/L) or high sensitivity cardiac troponin T =40 ng/L and dFLC =18 mg/dL
5.Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly

A comprehensive list of inclusion criteria can be found in the protocol.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

Exclusion Criteria

1.Non-AL amyloidosis
2.NT-proBNP >8500 pg/mL
3.Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma, except for malignancy biomarker of involved/and uninvolved serum free light chain ratio =100
4.Subject is eligible for and plans to undergo ASCT or organ transplant during the study
5.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
6.Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease
7.ECG evidence of acute ischemia or active conduction system abnormalities
8.Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1
9.Prior radiotherapy within 4 weeks of Month 1-Day 1
10.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
11.Waldenström's macroglobulinemia and/or immunoglobulin M monoclonal gammopathy

A comprehensive list of exclusion criteria can be found in the protocol.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Double-blind Phase<br>• To evaluate the efficacy of birtamimab plus standard of care compared to placebo plus standard of care when administered intravenously in Mayo Stage IV subjects with AL amyloidosis by assessing time to all-cause mortality.<br><br>Open-label Extension Phase<br>• To evaluate the long-term safety of birtamimab plus standard of care in Mayo Stage IV subjects with AL amyloidosis;Secondary Objective: To evaluate birtamimab plus standard of care compared to placebo plus standard of care on the following:<br>• Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance<br>• Change from baseline to Month 9 in health-related quality of life using the Short Form-36 questionnaire Version 2 (SF-36v2);Primary end point(s): Time to all-cause mortality during the Double-blind Phase;Timepoint(s) of evaluation of this end point: Time from the first dose of study drug until death or end of the Doubleblind Phase over 9 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Change from baseline to Month 9 of the Double-blind Phase in the 6MWT distance (meters)<br>•Change from baseline to Month 9 of the Double-blind Phase in the Physical Component Summary (PCS) score of the SF-36v2<br>;Timepoint(s) of evaluation of this end point: From baseline until Month 9 of the Double-blind Phase

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