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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 1 March 2021
Main ID:  NCT04512235
Date of registration: 10/08/2020
Prospective Registration: Yes
Primary sponsor: Caelum Biosciences
Public title: A Study to Evaluate the Effectiveness 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
Date of first enrolment: August 25, 2020
Target sample size: 267
Recruitment status: Recruiting
URL:  https://clinicaltrials.gov/show/NCT04512235
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).  
Phase:  Phase 3
Countries of recruitment
Australia Belgium Canada France Germany Greece Israel Italy
Japan Poland Russian Federation Spain United Kingdom United States
Contacts
Name:     Caelum Medical Monitor
Address: 
Telephone: +1 609-337-3010
Email: info@caelumbio.com
Affiliation: 
Key inclusion & exclusion criteria

Inclusion Criteria:

- Each patient must meet the following criteria to be enrolled in this study.

1. Provide written informed consent and be willing and able to comply with all study
procedures

2. Adult, 18 years and older

3. AL amyloidosis Mayo stage IIIa based on the 2013 European Modification of the
2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement
at the time of Screening

4. 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 ratio or

3. Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL

5. Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid
deposits by at least one of the following:

1. Immunohistochemistry or

2. Mass spectrometry or

3. Characteristic electron microscopy appearance

6. Cardiac involvement as defined by:

1. 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

2. At least one of the following:

i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or

ii. Echocardiogram demonstrating a mean left ventricular wall thickness > 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 MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis

7. Planned first-line treatment for plasma cell disorder is CyBorD administered as
Standard of Care (SoC)

8. Adequate bone marrow reserve and hepatic and renal function as demonstrated by:

1. Absolute neutrophil count = 1.0 x 109/L

2. Platelet count = 75 x 109/L

3. Hemoglobin = 9 g/dL

4. Total direct bilirubin = 2 times the upper limit of normal (x ULN) unless
due to Gilbert's syndrome.

5. Aspartate aminotransferase (AST) = 3 x ULN

6. Alanine aminotransferase (ALT) = 3 x ULN

7. Alkaline phosphatase (ALP) = 5 x ULN (except for patients with hepatomegaly
and isozymes specific to liver, rather than bone)

8. Estimated glomerular filtration rate (eGFR) = 15 mL/min

9. Women of childbearing potential (WOCBP) must have a negative pregnancy test
during Screening and must agree to use effective physician approved contraception
from Screening to 90 days following the last study drug administration

10. Men must be surgically sterile or must agree to use effective physician approved
contraception from Screening to 90 days following the last study drug
administration

Exclusion Criteria:

- Patients who meet any of the following criteria will not be permitted entry to the
study.

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 160 mg dexamethasone (or equivalent corticosteroid) since diagnosis of AL
amyloidosis and prior to randomization is allowed.

3. Meets the International Myeloma Working Group (IMWG) definition of multiple
myeloma or POEMS syndrome

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

5. Taking prednisone or its equivalent > 10 mg/day

6. Taking doxycycline

7. Receiving dialysis

8. Planned stem cell transplant during the first 6 months of protocol therapy. Stem
cell collection during the protocol therapy is permitted.

9. Have had myocardial infarction, uncontrolled angina, severe uncontrolled
ventricular arrhythmias within 6 months prior to screening or percutaneous
cardiac intervention with recent stent or coronary artery bypass grafting within
4 months prior to screening

10. Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening

11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area
< 1.0 cm2) or severe congenital heart disease

12. Have history of sustained ventricular tachycardia or aborted ventricular
fibrillation or a history of atrioventricular nodal or sinoatrial nodal
dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is
indicated but not placed. (Participants who do have a pacemaker or ICD are
allowed in the study.)

13. QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a
pacemaker may be included regardless of calculated QTc interval.

14. There is evidence of acute ischemia or active conduction system abnormalities
with the exception of any of the following:

1. First degree Atrioventricular (AV)-block

2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type)

3. Right or left bundle branch block

4. Atrial fibrillation with a controlled ventricular rate. (An uncontrolled
ventricular rate [i.e., > 110 beats per minute] determined by an average of
three beats in lead II or representative beats in lead II is not allowed)

15. Have had major surgery within 4 weeks of randomization or is planning major
surgery during the study. Patients with surgical procedures conducted under local
anesthesia may participate

16. There is active malignancy (including lymphoma) with the exception of any of the
following:

1. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ
cervical cancer

2. Adequately treated stage I cancer from which the patient is currently in
remission and has been in remission for > 2 years

3. Low-risk prostate c



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
AL Amyloidosis
Intervention(s)
Drug: CAEL-101
Drug: cyclophosphamide, bortezomib, and dexamethasone (CyBorD)
Other: Placebo
Primary Outcome(s)
Number of patients with treatment emergent adverse events as assessed by CTCAE v5.0 [Time Frame: 50 weeks]
Time from the first dose of study drug until death or end of study [Time Frame: 50 weeks]
Secondary Outcome(s)
Cardiac Improvement by Global Longitudinal Strain (GLS%) [Time Frame: 50 weeks]
Change in distance walked (in meters) during a six-minute walk test [Time Frame: 50 weeks]
Quality of Life (QOL) by the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS) [Time Frame: 50 weeks]
Quality of Life (QOL) by the Short Form-36 (SF-36) v2 Physical Component Score (PCS) [Time Frame: 50 weeks]
Secondary ID(s)
CAEL101-302
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
IQVIA Biotech
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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