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NCT04504825

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

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-25

Study Completion Date

2027-10-22

Brief Summary

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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 IIIb AL amyloidosis.

Detailed Description

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This is a double-blind, randomized, multicenter international Phase 3 study of CAEL-101 combined with standard of care (SoC) plasma cell dyscrasia (PCD) treatment versus placebo combined with SoC PCD treatment in Mayo stage IIIb PCD treatment-naïve AL amyloidosis patients. The primary evaluation treatment period (PETP) part of the study will stop when the last patient is randomized in the PETP plus 18 months. Approximately 124 patients will be enrolled using a 2:1 randomization ratio. Stratification will be based on geographic region across investigator sites. The primary endpoint is a composite endpoint of all-cause mortality and frequency of cardiovascular hospitalizations. Patients in both study intervention groups will be followed from randomization until death from any cause, heart transplant, left wall assist device (LVAD) implantation or until the end of study.

Conditions

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AL Amyloidosis

Keywords

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Plasma Cell Dyscrasia cyclophosphamide, bortezomib and dexamethasone (CyBorD) AL Amyloidosis Amyloid, Light chain Amyloidosis treatment-naïve Mayo Stage IIIb

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a double-blind, randomized, multicenter, international Phase 3 study of CAEL-101 combined with SoC PCD treatment versus placebo combined with SoC PCD treatment in Mayo stage IIIb PCD treatment-naïve AL amyloidosis patients.

Approximately 124 patients will be enrolled using a 2:1 randomization ratio and stratification will be based on geographic region across investigator sites.

The primary evaluation treatment period (PETP) part of the study will stop when the last patient is randomized in the PETP plus 18 months. Patients in both study intervention groups will be followed from randomization until death from any cause, heart transplant, left valve assist device (LVAD) implantation or until the end of study.

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

This is a double-blind, randomized, multicenter international Phase 3 study.

Study Groups

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CAEL-101 combined with SoC plasma cell dyscrasia

CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months. The study is divided into 2 parts, the Primary Evaluation Treatment period part and the Open-Label Extension period of Study.

Group Type EXPERIMENTAL

CAEL-101

Intervention Type DRUG

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.

cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

Intervention Type DRUG

According to institutional standard of care.

Placebo combined with SoC plasma cell dyscrasia

Patients randomized to receive placebo will receive 0.9% normal saline in an equivalent volume to a CAEL-101 infusion (approximately 250 cc). It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

Intervention Type DRUG

According to institutional standard of care.

Interventions

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CAEL-101

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

According to institutional standard of care.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* AL amyloidosis stage IIIb based on the European Modification of the 2004 Standard Mayo Clinic Staging (NT-proBNP \> 8,500 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/Immunofluorescence or
2. Mass spectrometry or
3. Characteristic electron microscopy appearance/Immunoelectron microscopy
* Cardiac involvement as defined by:

1. 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
2. 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

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 (e.g., 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 mol/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, 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott Swenson, MD

Role: STUDY_DIRECTOR

Alexion, AstraZeneca Rare Disease

Review additional registry numbers or institutional identifiers associated with this trial.

CAEL101-301

Identifier Type: -

Identifier Source: org_study_id

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

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

CAEL-101 combined with SoC plasma cell dyscrasia

CAEL-101

cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

Placebo combined with SoC plasma cell dyscrasia

Placebo

cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

Interventions

CAEL-101

Placebo

cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Alexion Pharmaceuticals, Inc.

Responsible Party

Principal Investigators

Scott Swenson, MD

Locations

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