A study to see how effective and safe NEO001 is when given together with the standard treatment (for plasma cell dyscrasia) in comparison to placebo together with the standard treatment in people with Light Chain (AL) Amyloidosis.
- Conditions
- ight chain (AL) amyloidosis involves a hematologic disorder caused by clonal plasma cells that produce misfolded immunoglobulin light chains. Overproduction of misfolded light chains results in both soluble, aggregated forms of light chains and insoluble,fibrillar deposits of abnormal AL protein (amyloid),in the tissues and organs. This can cause a range of symptoms and organ dysfunction including cardiac,renal,and hepatic dysfunction,gastrointestinal involvement and neuropathy and macroglossiaMedDRA version: 20.0Level: PTClassification code 10036673Term: Primary amyloidosisSystem Organ Class: 10021428 - Immune system disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2014-003865-11-FR
- Lead Sponsor
- Prothena Therapeutics Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 236
Subjects must meet all of the following criteria:
1. Aged = 18 years
2. Newly diagnosed and AL amyloidosis treatment naïve
3. Bone marrow consistent with plasma cell dyscrasia within 42 days prior to Month 1-Day 1
4. Confirmed diagnosis of AL amyloidosis by the following:
• Histochemical diagnosis of amyloidosis determined by polarizing light microscopy of green birefringent material in Congo red-stained tissue specimens OR characteristic electron microscopy appearance AND
• Confirmatory immunohistochemistry OR mass spectroscopy of AL amyloidosis
5. Confirmed diagnosis of AL amyloidosis by mass spectrometry of tissue biopsy if the subject meets any of the following:
• is black or African American
• is over 75 years of age with concurrent monoclonal gammopathy
• has a history of familial amyloidosis and has concurrent monoclonal gammopathy
6. Cardiac involvement as defined by all of the following:
• Past documented or presently noted 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
• Echocardiogram demonstrating a mean left ventricular wall thickness > 12 mm in the absence of other cardiac cause to explain wall thickening (such as hypertension or cardiac valvular disease)
• NT-proBNP = 650 pg/mL in the absence of renal failure or atrial fibrillation with an uncontrolled ventricular rate
7. Planned first-line chemotherapy contains bortezomib administered weekly and SC
8. Adequate bone marrow reserve, hepatic and renal function, as demonstrated by: absolute neutrophil count (ANC) = 1.0 x10^9/L
• platelet count = 75 x 10^9/L
• hemoglobin = 9 g/dL
• total bilirubin = 2 x upper limit of normal (ULN)
• aspartate aminotransferase (AST) / serum glutamic oxaloacetic transaminase (SGOT) = 3 x ULN
• alanine aminotransferase (ALT) / serum glutamic pyruvic transaminase (SGPT) = 3 x ULN
• alkaline phosphatase (ALP) = 5 x ULN (except for patients with hepatomegaly and isozymes specific to liver, rather than bone)
• estimated glomerular filtration rate (eGFR) = 30 mL/min
9. Seated systolic blood pressure 90-180 mmHg
10. Distance walked during 6MWT is =30 meters and =550 meters
11. Women of childbearing potential (WOCBP) must have two negative pregnancy tests during Screening, the second within 24 hours prior to the first administration of study drug and must agree to use physician-approved contraception from Screening to 30 days following the last study drug administration
12. Male subjects must be surgically sterile or must agree to use physician-approved contraception from Screening to 30 days following the last study drug administration
13. Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36
Subjects must meet none of the following criteria:
1. Non-AL amyloidosis
2. NT-proBNP > 8,500 pg/mL
3. Meets the International Myeloma Working Group (IMWG) definition of Multiple Myeloma (see Appendix 11)
*Note that subjects who meet the IMWG definition of symptomatic multiple myeloma with signs and/or symptoms attributable only to associated amyloidosis and who do not otherwise meet the criteria for diagnosis of smoldering myeloma are potentially eligible upon approval of the Sponsor.
4. Subject is eligible for and plans to undergo ASCT
5. Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would interfere with subject’s ability to safely receive treatment or complete study assessments
6. Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit
7. Severe valvular stenosis (e.g. aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease
8. ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
• First degree AV-block
• Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
• Right or left bundle branch block
• Atrial fibrillation with a controlled ventricular rate
Prior to randomization, any ECG screening abnormalities must be noted as not clinically significant” by the Investigator
9. Peripheral neuropathy assessed as National Cancer Institute-Common Terminology Criteria for Adverse Events ( NCI-CTCAE) Grade 2 with pain, Grade 3 or Grade 4
10. Subject is receiving oral or IV antibiotics, antifungals or antivirals within 1 week of Month 1-Day 1 with the exception of prophylactic oral agents
11. Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1
12. Prior radiotherapy within 4 weeks of Month 1-Day 1
13. Major surgery within 4 weeks of Month 1-Day 1 or planned major surgery during the study
14. Active malignancy with the exception of any of the following:
• Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
• Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for 2 years
• Stage I prostate cancer that does not require treatment
• Any other cancer from which the subject has been disease-free for = 2 years
15. History of Grade = 3 infusion-associated AEs or hypersensitivity to another monoclonal antibody, or known hypersensitivity to diphenhydramine (or an equivalent H1 antihistamine) or acetaminophen (or its equivalent, paracetamol)
16. Uncontrolled, active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection
17. Prior treatment with NEOD001
18. Treatment with another investigational agent within 30 days of Month 1-Day 1
19. Women who are pregnant or lactating
20. Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the Investigator, unacceptably increase the subject’s risk by participating in the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method