stage IIIb cardiac AL amyloidosis MedDRA version: 20.0 Level: PT Classification code 10007509 Term: Cardiac amyloidosis System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: CAEL-101
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not assigned
Current Sponsor code: CAEL-101
Other descriptive name: CHIMERIC FIBRIL-REACTIVE IGG1K MONOCLONAL ANT
Sponsors
Caelum Biosciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: • AL amyloidosis stage IIIb based on the 2013 European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement at the time of Screening • Measurable hematologic disease at Screening as defined by at least one of the following: • Involved/uninvolved free light chain difference (dFLC) > 4 mg/dL or • Involved free light chain (iFLC) > 4 mg/dL with abnormal ratio or • 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: • Immunohistochemistry or • Mass spectrometry or • Characteristic electron microscopy appearance • Cardiac involvement as defined by: • 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 • At least one of the following: • Endomyocardial biopsy demonstrating AL cardiac amyloidosis or • Echocardiogram demonstrating a mean left ventricular wall thickness > 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 • 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) administered as SoC 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 66 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: • Have any other form of amyloidosis other than AL amyloidosis • Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 160 mg dexamethasone (or equivalent corticosteroid) since diagnosis of AL amyloidosis and prior to randomization is allowed. • Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) (Appendix A) • Have supine systolic blood pressure 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 functional improvement as measured by the distance walked in the six-minute walk test (6MWT) • To assess quality of life as measured by the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) • To assess quality of life as measured by the Short Form 36 version 2 Physical Component Score (SF-36v2® PCS) • To assess cardiac improvement as measured by percent Global Longitudinal Strain (GLS%);Primary end point(s): The primary efficacy endpoint is overall survival and will be assessed as the time from first dose of study drug to the date of death. Patients living at the end of the study will be censored at their last known date alive. Patients who discontinue study treatment or the study prematurely will be included in the analysis (even if after discontinuation of study treatment or the study) using the death date or censoring time point, as appropriate. ;Timepoint(s) of evaluation of this end point: End of Treatment (EoT) and Follow-up every 12 weeks thereafter | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The four key secondary efficacy endpoints are: • Changes from baseline to Week 50 in the 6MWT distance • Changes from baseline to Week 50 in the KCCQ-OS • Changes from baseline to Week 50 in the SF-36 v2 PCS • Changes from baseline to Week 50 in GLS%;Timepoint(s) of evaluation of this end point: 6MWT, KCCQ-QS & SF-36: Weeks 1, 14, 26, 38 & 50. GLS% (echocardiogram): Screening (Week -4 to 0), Weeks 14, 26 & 50. | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Greece, Israel, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactEileen Daniel
Caelum Biosciences, Inc.
Outcome results
None listed