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Clinical Trials in the UK / NCT04512235
Active, not recruiting Phase 3

A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis (CARES)

NCT04512235 · tracked via the Priya Life Science UK tracker
Sponsor
Alexion Pharmaceuticals, Inc.
Phase
Phase 3
Started
2020-11-03
Last updated
2026-06-17

Condition(s) studied

AL Amyloidosis

Investigational drug(s) / intervention(s)

CAEL-101Placebocyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen

CAEL-101: The investigational product, CAEL-101, is formulated as a sterile liquid solution of protein plus excipients for dilution in a single-use, stoppered, glass vial. Each 10 mL vial contains 300 mg of CAEL-101 at a concentration of 30 mg/mL. CAEL-101 will be diluted with commercially available 0.9% Normal Saline.

Placebo: Commercially available 0.9% Normal Saline will be used as the placebo.

cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen: According to institutional standard of care.

Study summary

AL (or light chain) amyloidosis begins in the bone marrow where abnormal proteins misfold and create free light chains that cannot be broken down. These free light chains bind together to form amyloid fibrils that build up in the extracellular space of organs, affecting the kidneys, heart, liver, spleen, nervous system and digestive tract.

The primary purpose of this study is to determine whether CAEL-101, a monoclonal antibody that removes AL amyloid deposits from tissues and organs, improves overall survival, reduces cardiovascular related hospitalizations and it is safe and well tolerated in patients with stage IIIa AL amyloidosis.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Key Inclusion Criteria: * AL amyloidosis stage IIIa based on the European Modification of the 2004 Standard Mayo Clinic Staging who also have NT-proBNP \> 650 ng/L at the time of Screening * Measurable hematologic disease at Screening as defined by at least one of the following: 1. Involved/uninvolved free light chain difference (dFLC) \> 4 mg/dL or 2. Involved free light chain (iFLC) \> 4 mg/dL with abnormal Kappa/Lambda ratio or 3. 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: 1. Immunohistochemistry/Immunofluroescence 2. Mass spectrometry or 3. 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 a 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 from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of his PCD therapy, whichever is longer 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 2 weeks of a CyBorD-based PCD treatment after Screening laboratory samples are obtained and prior to randomization is allowed. * Has POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) 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 biopsy-proven (performed ≤ 3 months prior to signing the ICF) bony or extramedullary plasmacytoma AND 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 upper limit of normal (ULN) or \> 2.75 mmol/L (\> 11 mg/dL) OR ii. Renal insufficiency: creatinine clearance \< 40 mL per minute or serum creatinine \> 177 umol/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): skeletal radiography, computed tomography (CT), or positron emission tomography (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 5 mm 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

Primary outcome measure(s)

Trial sites (110)

FacilityCityRegionStatus
Research Site Scottsdale Arizona
Research Site Duarte California
Research Site Palo Alto California
Research Site San Francisco California
Research Site Jacksonville Florida
Research Site Weston Florida
Research Site Indianapolis Indiana
Research Site New Orleans Louisiana
Research Site Baltimore Maryland
Research Site Boston Massachusetts
Research Site Boston Massachusetts
Research Site Boston Massachusetts
Research Site Detroit Michigan
Research Site Rochester Minnesota
Research Site St Louis Missouri
Research Site New York New York
Research Site New York New York
Research Site Rochester New York
Research Site Chapel Hill North Carolina
Research Site Durham North Carolina
Research Site Winston-Salem North Carolina
Research Site Cleveland Ohio
Research Site Columbus Ohio
Research Site Portland Oregon
Research Site Philadelphia Pennsylvania
Research Site Nashville Tennessee
Research Site Dallas Texas
Research Site Houston Texas
Research Site Salt Lake City Utah
Research Site Seattle Washington
Research Site Madison Wisconsin
Research Site Milwaukee Wisconsin
Research Site Box Hill Australia
Research Site Murdoch Australia
Research Site Westmead Australia
Research Site Woolloongabba Australia
Research Site Linz Austria
Research Site Vienna Austria
Research Site Anderlecht Belgium
Research Site Leuven Belgium

+ 70 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04512235 on ClinicalTrials.gov ↗ ← All trials in the UK