2022-503073-11-00招募中3 期
A Phase 3, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of CAEL-101 and Plasma Cell Dyscrasia Treatment Versus Placebo and Plasma Cell Dyscrasia Treatment in Plasma Cell Dyscrasia Treatment-Naïve Patients with Mayo Stage IIIb AL Amyloidosis
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 43
- 主要终点
- A hierarchical combination of time to all-cause Mortality (ACM) and the frequency of cardiovascular hospitalizations (CVH). Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Changes from baseline in vital signs, weight, clinical laboratory tests, and 12-lead electrocardiograms (ECGs).
研究概览
简要总结
The primary objectives are:
- To determine if CAEL-101 and treatment for plasma cell dyscrasia (PCD) improves overall survival and/or decreases the frequency of cardiovascular hospitalizations in Mayo stage IIIb AL amyloidosis patients who are treatment naïve compared to treatment for PCD and placebo
- To evaluate the safety and tolerability of CAEL-101 in combination with treatment for PCD and placebo
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •AL amyloidosis stage IIIb based on the European Modification of the 2004 Standard Mayo Clinic Staging at the time of Screening, which includes NT-proBNP > 8,500 ng/L.
- •Measurable hematologic disease at Screening as defined by at least one of the following: a. Involved/uninvolved free light chain difference (dFLC) > 4 mg/dL OR b. Involved free light chain (iFLC) > 4 mg/dL with abnormal Kappa/Lambda ratio OR c. Serum protein electrophoresis (SPEP) m-spike > 0.5 g/dL
- •Histopathological diagnosis of amyloidosis based on polarizing light microscopy of green bi-refringent material in Congo red stained tissue specimens AND confirmation of AL derived amyloid deposits by at least one of the following: a. Immunohistochemistry/Immunofluorescence OR b. Mass spectrometry OR c. Characteristic electron microscopy appearance/Immunoelectron microscopy
- •Cardiac involvement as defined by: a. Documented clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure AND b. At least one of the following: I. Endomyocardial biopsy demonstrating AL cardiac amyloidosis OR ii. Echocardiogram demonstrating a mean left ventricular wall thickness (calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening OR iii. Cardiac magnetic resonance imaging (MRI) with gadolinium contrast agent diagnostic of cardiac amyloidosis
- •Planned first-line treatment for plasma cell dyscrasia is cyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC.
- •Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer
- •Men must be surgically sterile or must agree to use highly effective contraception and refrain from donating sperm from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of their PCD therapy, whichever is longer
排除标准
- •Have any other form of amyloidosis other than AL amyloidosis
- •Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 2 weeks of a CyBorD-based PCD treatment after Screening laboratory samples are obtained and prior to randomization is allowed.
- •Has POEMS syndrome OR multiple myeloma defined as clonal bone marrow plasma cells > 10% from a bone marrow biopsy (performed ≤ 3 months prior to signing the ICF or during Screening) OR biopsy-proven (performed ≤ 3 months prior to signing the ICF or during Screening) bony or extramedullary plasmacytoma AND any one or more of the following CRAB features: a. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, (eg, multiple myeloma and POEMS syndrome), specifically: i. Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the ULN or > 2.75 mmol/L (> 11 mg/dL) OR ii. Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177 μmol/L (> 2 mg/dL) OR iii. Anemia: hemoglobin value of > 20 g/L below the lowest limit of normal, or a hemoglobin value < 100 g/L OR iv. Bone lesions: one or more osteolytic lesion on imaging tests (performed ≤ 3 months prior to signing the ICF or during Screening): skeletal radiography, CT, or PET/CT, or MRI. If bone marrow has < 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement OR b. Any one of the following biomarkers of malignancy: i. 60% or greater clonal plasma cells on bone marrow examination OR ii. More than one focal lesion on MRI that is at least 5mm or greater in size
- •Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion
结局指标
主要结局
A hierarchical combination of time to all-cause Mortality (ACM) and the frequency of cardiovascular hospitalizations (CVH). Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Changes from baseline in vital signs, weight, clinical laboratory tests, and 12-lead electrocardiograms (ECGs).
A hierarchical combination of time to all-cause Mortality (ACM) and the frequency of cardiovascular hospitalizations (CVH). Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Changes from baseline in vital signs, weight, clinical laboratory tests, and 12-lead electrocardiograms (ECGs).
次要结局
- Time to ACM in Primary Evaluation Treatment Period (PETP)
- Frequency of CVH in PETP
- Changes from baseline to Week 50 in the KCCQ-OS.
- Change from baseline to Week 50 in NTproBNP
- Changes from baseline to Week 50 in GLS%.
- Changes from baseline to Week 50 in the 6MWT
- Change from baseline to Week 50 in the SF-36v2 PCS
研究者
European Clinical Trial Information
Scientific
Alexion Pharmaceuticals Inc.
研究点 (43)
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