A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis (CARES)
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
1 other identifier
interventional
281
18 countries
108
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2020
Longer than P75 for phase_3
108 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 10, 2020
CompletedFirst Posted
Study publicly available on registry
August 13, 2020
CompletedStudy Start
First participant enrolled
November 3, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 8, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
April 8, 2027
ExpectedMarch 17, 2026
March 1, 2026
4.4 years
August 10, 2020
March 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
A hierarchical combination of Time to All-cause Mortality and Frequency of Cardiovascular hospitalizations
From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 54 months)
Number of Participants with Treatment emergent Adverse Events (TEAEs)
From date of randomization to Primary Evaluation Treatment Period (PETP) (up to 59 months)
Secondary Outcomes (7)
Time to All-cause Mortality
From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 54 months)
Frequency of cardiovascular-related hospitalizations (CVH)
From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 54 months)
Change From Baseline to Week 50 in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)
Baseline, Week 50
Change from Baseline to Week 50 in N-Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in blood samples
Baseline, Week 50
Change From Baseline to Week 50 in Global Longitudinal Strain (GLS%)
Baseline, Week 50
- +2 more secondary outcomes
Study Arms (2)
CAEL-101 combined with SoC plasma cell dyscrasia
EXPERIMENTALThe 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 combined with SoC plasma cell dyscrasia
PLACEBO COMPARATORPatients 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.
Interventions
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.
Commercially available 0.9% Normal Saline will be used as the placebo.
According to institutional standard of care.
Eligibility Criteria
You may qualify if:
- 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:
- Involved/uninvolved free light chain difference (dFLC) \> 4 mg/dL or
- Involved free light chain (iFLC) \> 4 mg/dL with abnormal Kappa/Lambda 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/Immunofluroescence
- Mass spectrometry or
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (110)
Research Site
Scottsdale, Arizona, 85259, United States
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Duarte, California, 91010, United States
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Palo Alto, California, 94304, United States
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San Francisco, California, 94143, United States
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Jacksonville, Florida, 32224, United States
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Weston, Florida, 33331, United States
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Indianapolis, Indiana, 46202, United States
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New Orleans, Louisiana, 70112, United States
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Baltimore, Maryland, 21201, United States
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Boston, Massachusetts, 02111, United States
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Boston, Massachusetts, 02118, United States
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Boston, Massachusetts, 02215, United States
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Detroit, Michigan, 48201, United States
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Rochester, Minnesota, 55905, United States
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St Louis, Missouri, 63110, United States
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New York, New York, 10032, United States
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New York, New York, 10065, United States
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Rochester, New York, 14642, United States
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Chapel Hill, North Carolina, 27599, United States
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Durham, North Carolina, 27705, United States
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Winston-Salem, North Carolina, 27157, United States
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Cleveland, Ohio, 44195, United States
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Columbus, Ohio, 43210, United States
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Portland, Oregon, 97239, United States
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Philadelphia, Pennsylvania, 19104, United States
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Nashville, Tennessee, 37232, United States
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Dallas, Texas, 75390, United States
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Houston, Texas, 77030, United States
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Salt Lake City, Utah, 84112, United States
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Seattle, Washington, 98109, United States
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Madison, Wisconsin, 53792, United States
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Milwaukee, Wisconsin, 53226, United States
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Box Hill, 3128, Australia
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Murdoch, WA6150, Australia
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Westmead, 2145, Australia
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Woolloongabba, 4102, Australia
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Linz, 4020, Austria
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Vienna, 1090, Austria
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Anderlecht, 1070, Belgium
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Leuven, 3000, Belgium
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Porto Alegre, 90110-270, Brazil
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Ribeirão Preto, 14051-140, Brazil
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Salvador, 41253-190, Brazil
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Calgary, Alberta, T2N 4N2, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Beijing, 100034, China
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Beijing, 100730, China
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Guangzhou, 510180, China
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Hangzhou, 310009, China
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Shanghai, 200032, China
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Suzhou, 215006, China
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Wenzhou, 325000, China
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Wuhan, 430022, China
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Ostrava Poruba, 708 52, Czechia
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Prague, 12808, Czechia
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Caen, 14033, France
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Créteil, 94000, France
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Dijon, 21079, France
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Lille, 59037, France
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Limoges, 87042, France
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Marseille, 13009, France
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Paris, 75010, France
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Pessac, 33604, France
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Pierre-Bénite, 69310, France
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Poitiers, 86021, France
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Rennes, 35033, France
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Toulouse, 31100, France
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Tours, 37044, France
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Berlin, 12203, Germany
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Düsseldorf, 40225, Germany
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Essen, 45147, Germany
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Hamburg, 22767, Germany
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Heidelberg, 69120, Germany
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Würzburg, 97080, Germany
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Athens, 11528, Greece
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Rio, 26504, Greece
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Thessaloniki, 54636, Greece
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Haifa, 31096, Israel
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Jerusalem, 91120, Israel
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Petah Tikva, 49100, Israel
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Tel Aviv, 64239, Israel
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Tel Litwinsky, 52621, Israel
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Brescia, 25123, Italy
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Fukushima, 960-1295, Japan
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Kanazawa, 920-8641, Japan
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Kashiwa-shi, 277-8567, Japan
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Kita-ku, 603-8151, Japan
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Kumamoto, 860-8556, Japan
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Matsumoto-shi, 390-8621, Japan
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Nagoya, 467-8602, Japan
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Shibuya-ku, 150-8935, Japan
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Gdansk, 80-214, Poland
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Warsaw, 01-748, Poland
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Saint Petersburg, 197022, Russia
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Seoul, 03722, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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Barcelona, 08036, Spain
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Barcelona, 8035, Spain
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Gijón, 33394, Spain
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Granada, 18014, Spain
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Madrid, 28003, Spain
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Madrid, 28040, Spain
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Majadahonda, 28222, Spain
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Pamplona, 31008, Spain
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Salamanca, 37007, Spain
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Seville, 41013, Spain
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Valencia, 46009, Spain
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Glasgow, G12 0YN, United Kingdom
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London, NW1 2PG, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Scott Swenson, MD
Alexion, AstraZeneca Rare Disease
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- This is a double-blind, randomized, multicenter international Phase 3 study.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 10, 2020
First Posted
August 13, 2020
Study Start
November 3, 2020
Primary Completion
April 8, 2025
Study Completion (Estimated)
April 8, 2027
Last Updated
March 17, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
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.