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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
125
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.
Research Site
Duarte, California, United States
Research Site
Palo Alto, California, United States
Research Site
San Francisco, California, United States
Research Site
Weston, Florida, United States
Research Site
Indianapolis, Indiana, United States
Research Site
A hierarchical combination of Time to All-cause Mortality and Frequency of Cardiovascular hospitalizations
Time frame: From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 51 months)
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Time frame: From date of randomization to Primary Evaluation Treatment Period (PETP) (up to 56 months)
Time to All-cause Mortality
Time frame: From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 51 months)
Frequency of cardiovascular-related hospitalizations (CVH)
Time frame: From the date of randomization to date of death or Primary Evaluation Treatment Period (PETP) (up to 51 months)
Change from Baseline to week 50 in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)
A 23-item self-administered questionnaire that quantifies physical function, symptoms, social function, self-efficacy and knowledge and quality of life. It requires an average of 4-6 minutes to complete and uses an ordinal, adjectival (Likert) scale
Time frame: Baseline, Week 50
Change from Baseline to Week 50 in N - Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in blood samples
To assess improvement in cardiomyopathy as measured by NT-proBNP. For each participant, blood sample will be assayed for NT-proBNP, comparing the participant's baseline value over time to assess improvement in the heart by reduced amyloidosis as measured by an increase or decrease in amyloidosis-related biomarkers: NT-proBNP.
Time frame: Baseline, Week 50
Change from Baseline to Week 50 in Cardiac Improvement by Global Longitudinal Strain (GLS%)
To assess improvement in heart function as measured by percent Global Longitudinal Strain (GLS%). GLS% is a non-invasive imaging technique to assess heart function where a higher/lower percentage is indicative of improvement.
Time frame: Baseline, Week 50
Change from Baseline to Week 50 in distance walked (in meters) during a six-minute walk test (6MWT)
Time frame: Baseline, Week 50
Change from Baseline to Week 50 the Short Form-36 (SF-36) v2 Physical Component Score (PCS)
A self-administered questionnaire containing 36 items that measures health on functional status, well-being and overall evaluation of health in 8 domains. It requires approximately 5 minutes to complete and uses scaled, ordinal responses (e.g., All of the time, Most of the time, A good bit of the time, etc.)
Time frame: Baseline, Week 50
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New Orleans, Louisiana, United States
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Boston, Massachusetts, United States
Research Site
Boston, Massachusetts, United States
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Boston, Massachusetts, United States
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Detroit, Michigan, United States
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