The RAIN Study, a Multicenter Randomized Double-blind Phase 2b Study of NEOD001 in Previously Treated Subjects With Systemic Light-chain (AL) Amyloidosis and Persistent Renal Involvement
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 9
- 主要终点
- Confirmed Renal Response After Treatment With NEOD001
研究概览
简要总结
This is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, two-arm, parallel-group efficacy and safety study of NEOD001 as a single agent administered intravenously in adults with AL amyloidosis who have a maintained hematologic response to their most recent treatment for AL amyloidosis (e.g., chemotherapy, autologous stem cell transplant [ASCT]) and have persistent renal dysfunction.
详细描述
This is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, two-arm, parallel-group efficacy and safety study of NEOD001 as a single agent administered intravenously in adults with AL amyloidosis who have a maintained hematologic response to their most recent treatment for AL amyloidosis (e.g., chemotherapy, autologous stem cell transplant [SCT]) and have persistent renal dysfunction. Subject screening will occur during the 28 days prior to the first administration of study drug (i.e. month 1 day 1). If screening assessments are completed and all eligibility requirements are met, the subject will be enrolled. Study visits will occur every 28 days based on scheduling from month 1 day 1. A ±5-day window is allowed for visits starting after month 1. Subjects may receive up to 12 infusions of study drug. Subjects who discontinue study drug before the initial End of Study (EOS) visit should have an Early Treatment Discontinuation (ETD) Visit 30 (±5) days after their final administration of study drug. After completing 12 months of treatment and the confirmatory EOS visit, a subject may enter an open-label extension (OLE) study, during which subjects will receive active treatment with NEOD001 for 12 months and may receive concurrent chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years of age or older
- •Biopsy-proven diagnosis of AL amyloidosis by immunohistochemistry or mass spectroscopy of a tissue biopsy excluding bone marrow
- •Screening renal biopsy for RAIN confirming AL amyloidosis as exclusive or dominant cause of renal damage
- •Persistent renal involvement from diagnosis with proteinuria (predominantly albumin) > 500mg/day in a 24-hour urine collection
- •CKD 1 to 3 (eGFR > 30)
- •≥1 prior systemic hematologic therapy for a free light chain (FLC) producing hematologic malignancy underlying the initial diagnosis of AL amyloidosis with at least a partial FLC response (PR, VGPR, CR) to treatment deemed stable and not requiring further treatment
- •ECOG Performance Status ≤ 2
- •Clinical laboratory values:
- •Absolute neutrophil count > 1000/μL
- •Platelet count > 75,000/μL
- •Total bilirubin ≤ 1.5X ULN
- •Alkaline phosphatase ≤ 5X ULN
- •NT-proBNP < 1800 pg/mL
- •Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
排除标准
- •Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis
- •Female patients who are lactating, breastfeeding, or pregnant
- •Patients who have not been treated or who have received chemotherapy within 6 months, or SCT within 12 months, for the light-chain producing hematologic disease causing AL amyloidosis, at the time of the first dose of NEOD001 (month 1 day 1)
- •Patients who at initial diagnosis or later met the International Myeloma Working Group (IMWG) definition of active multiple myeloma requiring therapy (Appendix 3)
- •Patients whose screening renal biopsies for RAIN show dominant causes of renal damage not related to AL amyloidosis
- •Medically documented cardiac syncope, uncompensated congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive atrial or ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically significant uncompensated autonomic insufficiency
- •Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Ongoing or active infection, known HIV positive, known to be hepatitis B surface antigen-positive or has known or suspected active hepatitis C infection.
- •Psychiatric illness/social situations that would limit compliance with study requirements
研究组 & 干预措施
NEOD001
Study Drug given IV every 28 days at 24mg/kg
干预措施: NEOD001 (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Confirmed Renal Response After Treatment With NEOD001
时间窗: Baseline to 13 Months
A renal response is a ≥ 30% reduction in proteinuria in the absence of a ≥ 25% decrease in eGFR. A confirmed renal response is one that has been documented as present one month after 12 monthly treatments.
次要结局
- Measured GFR at Study Entry(Baseline)
- Time to eGFR ≤ 15 or Dialysis(Baseline to 13 Months)
- Time to ≥ 40% Reduction in eGFR(Baseline to 13 Months)
- All Cause of Mortality at 26 Months(Baseline to 26 months)
- Time to CKD 4 or 5(Baseline to 13 Months)
- Time to Doubling of Creatinine(Baseline to 13 Months)
- Renal Response in Patients With Maintained Hematologic Responses After 24 Monthly Treatments.(Baseline to 26 months)