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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04512235




Registration number
NCT04512235
Ethics application status
Date submitted
10/08/2020
Date registered
13/08/2020

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis
Scientific 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
Secondary ID [1] 0 0
CAEL101-302
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
AL Amyloidosis 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Blood 0 0 0 0
Other blood disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CAEL-101
Other interventions - Placebo
Treatment: Drugs - cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen

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. It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months.

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). It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months.


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

Treatment: Drugs: cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen
According to institutional standard of care.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
A hierarchical combination of Time to All-cause Mortality and Frequency of Cardiovascular hospitalizations
Timepoint [1] 0 0
From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 54 months)
Primary outcome [2] 0 0
Number of Participants with Treatment emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
From date of randomization to Primary Evaluation Treatment Period (PETP) (up to 59 months)
Secondary outcome [1] 0 0
Time to All-cause Mortality
Timepoint [1] 0 0
From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 54 months)
Secondary outcome [2] 0 0
Frequency of cardiovascular-related hospitalizations (CVH)
Timepoint [2] 0 0
From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 54 months)
Secondary outcome [3] 0 0
Change From Baseline to Week 50 in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)
Timepoint [3] 0 0
Baseline, Week 50
Secondary outcome [4] 0 0
Change from Baseline to Week 50 in N-Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in blood samples
Timepoint [4] 0 0
Baseline, Week 50
Secondary outcome [5] 0 0
Change From Baseline to Week 50 in Global Longitudinal Strain (GLS%)
Timepoint [5] 0 0
Baseline, Week 50
Secondary outcome [6] 0 0
Change From Baseline to Week 50 in Distance Walked (in Meters) during a Six-minute Walk Test (6MWT)
Timepoint [6] 0 0
Baseline, Week 50
Secondary outcome [7] 0 0
Change From Baseline to Week 50 in the Short Form-36 (SF-36) Version 2 (v2) Physical Component Score (PCS)
Timepoint [7] 0 0
Baseline, Week 50

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
24/09/2027
Actual
Sample size
Target
Accrual to date
Final
281
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Box Hill
Recruitment hospital [2] 0 0
Research Site - Murdoch
Recruitment hospital [3] 0 0
Research Site - Westmead
Recruitment hospital [4] 0 0
Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
WA6150 - Murdoch
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
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Florida
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Indiana
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United States of America
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Louisiana
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United States of America
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Maryland
Country [7] 0 0
United States of America
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New York
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North Carolina
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Oregon
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Linz
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Vienna
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Wuhan
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Shibuya-ku
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Korea, Republic of
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Seoul
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Poland
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Gdansk
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Russian Federation
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Madrid
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Pamplona
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Salamanca
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Sevilla
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Valencia
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United Kingdom
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Glasgow
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Scott Swenson, MD
Address 0 0
Alexion, AstraZeneca Rare Disease
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Each patient will be assigned a unique identifier after signing the Informed Consent Form (ICF). Patient numbers will not be reassigned. Any patient records or datasets transferred to the Sponsor must contain only the unique identifier and must not include patient names or any information which would make the patient identifiable. Patients will be informed that their personal study-related data will be used by the Sponsor in accordance with local data protection laws and that their medical records may be examined by representatives of the Sponsor, Institutional Review Board (IRB)/Independent Ethics Committee (IEC) members and by inspectors from regulatory authorities. Study monitors will inspect all documents and records that are required to be maintained by the Investigator for this study.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04512235