stage IIIb cardiac AL amyloidosis MedDRA version: 20.0 Level: PT Classification code 10007509 Term: Cardiac amyloidosis System Organ Class: 10007541 - Cardiac disorders
Conditions
Sponsors
Alexion Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: 1. AL amyloidosis stage IIIb based on the European Modification of the 2004 Standard Mayo Clinic Staging at the time of Screening 2. 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 3. 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 b. Mass spectrometry c. Characteristic electron microscopy appearance/Immunoelectron microscopy 4. 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 5. Planned first-line treatment for plasma cell dyscrasia is cyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC. 6. 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 anti-PCD therapy, whichever is longer 7. 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 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 74 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: 1. Have any other form of amyloidosis other than AL amyloidosis 2. 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. 3. 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, 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 177 mol/L (> 2 mg/dL) OR - iii. Anemia: hemoglobin value of > 20 g/L below the lowest limit of normal, or a hemoglobin value 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are: • To determine if CAEL-101 and treatment for plasma cell dyscrasia improves overall survival in Mayo stage IIIb AL amyloidosis patients who are treatment naïve compared to treatment for plasma cell dyscrasia alone • To evaluate the safety and tolerability of CAEL-101 in combination with treatment for plasma cell dyscrasia;Secondary Objective: The key secondary objectives in this study are: •To assess quality of life as measured by the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) •To assess cardiac improvement as measured by percent Global Longitudinal Strain (GLS%) •To assess functional improvement as measured by the distance walked in the six-minute walk test (6MWT) •To assess quality of life as measured by the Short Form 36 version 2 Physical Component Score (SF-36v2® PCS) ;Primary end point(s): The primary efficacy endpoint is the time to all-cause mortality and will be assessed from the date of randomization to the date of death (for patients who died) or EOS. Patients living at the end of the study will be censored at their last known date recorded. Patients who prematurely discontinue study treatment or withdraw early from the study will be included in the analysis (even after discontinuation of study treatment or the study) using the date of death or censoring time point (i.e., last known date recorded), as appropriate.;Timepoint(s) of evaluation of this end point: End of Treatment (EoT) and Follow-up every 12 weeks thereafter. The primary endpoint is also evaluated during the Treatment Period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The four key secondary efficacy endpoints are : • Changes from baseline to Week 50 in the KCCQ-OS • Changes from baseline to Week 50 in GLS% • Changes from baseline to Week 50 in the 6MWT distance • Changes from baseline to Week 50 in the SF-36 v2 PCS;Timepoint(s) of evaluation of this end point: • KCCQ-OS & SF-36: Weeks 1, 14, 26, 38 & 50. • GLS% (echocardiogram): Screening (Week -4 to 0), Weeks 14, 26 & 50. • 6MWT : Screening (Week-4 to 0), Weeks 14, 26, 38 & 50. | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Czechia, Czech Republic, France, Germany, Greece, Israel, Italy, Japan, Korea, Democratic People's Republic of, Netherlands, Poland, Russian Federation, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactEuropean Clinical Trial Information
Alexion Europe SAS
Outcome results
None listed