A double-blind study to evaluate the effectiveness and safety of CAEL-101 in patients with AL amyloidosis.

• Register: EUCTR
• Last refreshed on: 18 June 2024
• Main ID: EUCTR2019-004254-28-DE
• Date of registration: 09/09/2020
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, Inc.
• Public title: A double-blind study to evaluate the effectiveness and safety of CAEL-101 in patients with 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 IIIb AL Amyloidosis
• Date of first enrolment: 23/12/2020
• Target sample size: 124
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004254-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, Czechia, France, Germany, Greece, Israel, Italy, Japan, Korea, Democratic People's Republic of, Netherlands, Poland, Russian Federation, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

Key inclusion & exclusion criteria

Inclusion criteria:
Key Inclusion Criteria:
1. AL amyloidosis stage IIIb based on the European Modification of the 2004 Standard Mayo Clinic Staging at the time of Screening, which includes NT-proBNP > 8,500 ng/L.
2. 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
3. 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/Immunofluorescence OR
b. Mass spectrometry OR
c. Characteristic electron microscopy appearance/Immunoelectron microscopy
4. 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
5. Planned first-line treatment for plasma cell dyscrasia is cyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC.
6. 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 anti-PCD therapy, whichever is longer
7. 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 74
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
Key Exclusion Criteria:
1. Have any other form of amyloidosis other than AL amyloidosis
2. 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.
3. Has POEMS 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 during Screening) OR biopsy-proven (performed = 3 months prior to signing the ICF or during Screening) bony or extramedullary plasmacytoma AND any 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 PEOMS 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 µmol/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 or during Screening): 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
4. 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

stage IIIb cardiac AL amyloidosis
MedDRA version: 20.0 Level: PT Classification code 10007509 Term: Cardiac amyloidosis System Organ Class: 10007541 - Cardiac disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: CAEL-101
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not assigned
Current Sponsor code: CAEL-101
Other descriptive name: Ch11-1F4 (NSC-711516)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: End of Treatment (EoT) and Follow-up every 12 weeks thereafter. The primary endpoint is also evaluated during the Treatment Period.

Primary end point(s): The primary efficacy endpoint is the time to all-cause mortality and will be assessed from randomization to the date of death (for patients who died) or to the end of the Primary Evaluation Treatment Period (PETP). Patients living at the End of Study (EoS) will be censored at their last known date recorded. Patients who prematurely discontinue study treatment or withdraw from the study will be included in the analysis (even after discontinuation of study treatment or the study) using the date of death or censoring time point (i.e., last known date recorded), as appropriate.

Secondary Objective: The key secondary objectives in this study are:
•To assess quality of life (QoL) as measured by the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)
•To assess cardiac improvement as measured by percent Global Longitudinal Strain (GLS%)
•To assess functional improvement as measured by the distance walked in the six-minute walk test (6MWT)
•To assess quality of life as measured by the Short Form 36 Health Survey version 2 Physical Component Score (SF-36v2® PCS)

Main Objective: The primary objectives are:
• To determine if CAEL-101 and treatment for plasma cell dyscrasia (PCD) improves overall survival in Mayo stage IIIb AL amyloidosis patients who are treatment naïve compared to treatment for PCD alone
• To evaluate the safety and tolerability of CAEL-101 in combination with treatment for PCD

Secondary Outcome(s)

Secondary end point(s): The four key secondary efficacy endpoints are :
• Changes from baseline to Week 50 in the KCCQ-OS
• Changes from baseline to Week 50 in GLS%
• Changes from baseline to Week 50 in the 6MWT distance
• Changes from baseline to Week 50 in the SF-36 v2 PCS

Timepoint(s) of evaluation of this end point: • KCCQ-OS & SF-36: Weeks 1, 14, 26, 38 & 50.
• GLS% (echocardiogram): Screening (Week -4 to 0), Weeks 14, 26 & 50.
• 6MWT : Screening (Week-4 to 0), Weeks 14, 26, 38 & 50.

Secondary ID(s)

NCT04504825

CAEL101-301

2019-004254-28-FR

Source(s) of Monetary Support

Alexion Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 23/12/2020
Contact: