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

Study identifier:CAEL101-302

ClinicalTrials.gov identifier:NCT04512235

EudraCT identifier:N/A

CTIS identifier:N/A

Recruitment Complete

Official Title

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 IIIa AL Amyloidosis

Medical condition

AL Amyloidosis

Phase

Phase 3

Healthy volunteers

Study drug

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

Sex

All

Actual Enrollment

281

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 12 Nov 2020

Estimated Primary Completion Date: 28 Feb 2024

Estimated Study Completion Date: 12 Jul 2024

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2024 by Alexion Pharmaceuticals, Inc.

Collaborators

Inclusion and exclusion criteria

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:
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/Immunofluroescence
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 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

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

No locations available

Arms	Assigned Interventions
Experimental: CAEL-101 combined with SoC plasma cell dyscrasia The study is divided into 2 parts, the Primary Study and the Open-Label Extension Study. CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. The minimum planned treatment time for each patient will be at least 50 weeks or until the patient’s death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event driven study, the study will continue, and all patients will continue to receive study treatment until at least 88 deaths have been observed.	Drug: 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. Other Name: Anselamimab Drug: cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen According to institutional standard of care. Other Name: Anselamimab
Placebo Comparator: 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). The minimum planned treatment time for each patient will be at least 50 weeks or until the patient’s death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event driven study, the study will continue, and all patients will continue to receive study treatment until at least 88 deaths have been observed.	Other: Placebo Commercially available 0.9% Normal Saline will be used as the placebo. Drug: cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen According to institutional standard of care. Other Name: Anselamimab

Arms

Assigned Interventions

Experimental: CAEL-101 combined with SoC plasma cell dyscrasia
The study is divided into 2 parts, the Primary Study and the Open-Label Extension Study. CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. The minimum planned treatment time for each patient will be at least 50 weeks or until the patient’s death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event driven study, the study will continue, and all patients will continue to receive study treatment until at least 88 deaths have been observed.

Drug: 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.

Other Name: Anselamimab

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

Other Name: Anselamimab

Placebo Comparator: 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). The minimum planned treatment time for each patient will be at least 50 weeks or until the patient’s death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event driven study, the study will continue, and all patients will continue to receive study treatment until at least 88 deaths have been observed.

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

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

Other Name: Anselamimab

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Scott Swenson

Alexion, AstraZeneca Rare Disease

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

Official Title

Medical condition

Phase

Healthy volunteers

Study drug

Sex

Actual Enrollment

Study type

Age

Date

Study design

Verification:

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Contacts

Contact

Investigators

Principal Investigator