Rain (Renal AL Amyloid Involvement And NEOD001): A Multicenter, Randomized, Phase 2b Study of NEOD001 in Previously Treated Subjects With Systemic AL Amyloidosis and Persistent Renal Involvement

Background: Systemic AL amyloidosis (AL) is a rare disease in which clonal plasma cells produce misfolded light chains that deposit in vital structures such as the heart and kidneys leading to progressive organ failure. Despite the achievement of hematologic responses, organ improvement is not assured. NEOD001 is a humanized monoclonal antibody that targets the abnormal light chains, promoting clearance of amyloid fibrils. Patients and Methods: Tufts Medical Center is sponsoring the RAIN trial: a randomized, placebo-controlled, phase 2b efficacy and safety study evaluating single agent NEOD001 versus placebo in patients with systemic AL amyloidosis who have achieved a stable hematologic response to prior therapy but still exhibit persistent kidney disease (> 500 mg of protein daily). Nine centers of excellence will participate across the country. NEOD001 (24mg/kg) or placebo will be administered every 28 days for 12 months. In an expansion phase, subjects will have the choice to receive active treatment with NEOD001 for an additional 12 months. We plan to randomize 100 subjects, 50 in each arm. The primary endpoint is achievement of a renal response defined as a > 30% reduction in proteinuria in the absence of a > 25% reduction in eGFR. Secondary endpoints include time to CKD 4 or 5, to eGFR < 15 mL/min/1.73 m² or dialysis, to doubling of creatinine and to > 40% reduction in eGFR. Ancillary studies will focus on patient-reported outcomes and on histologic and molecular assessments using pre-treatment renal biopsies that may identify predictors of renal outcome. We anticipate the first patient will be enrolled in early July 2017.

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