AL amyloidosis with hepatic involvement MedDRA version: 20.0 Level: PT Classification code 10075251 Term: Hepatic amyloidosis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Name: NEOD001
Product Code: NEOD001
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: NEOD001
Other descriptive name: Humanized IgG1, kappa anti-serum amyloid A and a
Sponsors
FONDAZIONE I.R.C.C.S. POLICLINICO SAN MATTEO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years 2. Confirmed diagnosis of systemic AL amyloidosis by the following: a. histochemical diagnosis of amyloidosis determined by polarizing light microscopy of green birefrigent material in Congo red-stained tissue specimens OR characteristic electron microscopy appearance AND b. confirmatory electron microscopy immunohistochemistry OR mass spectroscopy of AL amyloidosis 3. Hepatic involvement and measurable liver disease as defined by hepatomegaly (total liver span of >15 cm) by CT or alkaline phosphatase >2 times the upper limit of normal [× ULN]) 4. Stable disease defined as no change in the clonal status and liver involvement during the last 6 months 5. Seated systolic blood pressure 100-180 mmHg 6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days prior to the first administration of study drug and agree to use highly effective physician-approved contraception from 30 days prior to the first study drug administration to 90 days following the last study drug administration 7. Males must be surgically sterile or must agree to use highly effective physician-approved contraception from 30 days prior to the first study drug administration to 90 days following the last study drug administration 8. 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 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Non-AL amyloidosis 2. Advanced cardiac disease as defined by cardiac troponin I >0.1 ng/mL (or troponin T >0.035 ng/mL, or high-sensitivity troponin T >77 ng/L) AND NT-proBNP >8,500 ng/L 3. Severe renal disease as defined by estimated glomerular filtration rate (eGFR) <30 mL/min 4. End stage liver disease as defined by total bilirubin 5 × ULN 5. Meets any of the following diagnostic criteria for symptomatic multiple myeloma: • lytic lesions on skeletal survey or computerized tomography (CT) scan • plasmacytoma • bone marrow plasma cells =30% • hypercalcemia • anemia without explanation Note: subjects who meet the International Myeloma Working Group (IMWG) definition of symptomatic multiple myeloma with symptoms attributable only to associated amyloidosis are potentially eligible 6. Eligible for and plans to undergo ASCT or other chemotherapy 7. 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 8. 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 9. ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following: • 1st degree AV-block • 2nd degree AV-block Type 1 (Mobitz Type 1/ Wenckebach type) • Right bundle branch block • Atrial fibrillation with a controlled ventricular rate 10. Received any of the following within the specified time frame prior to the first administration of study drug (ie, Month 1 Day 1 Visit): • Oral or intravenous antibiotics, antifungals, or antivirals within 1 week, with the exception of prophylactic oral agents (administration of doxycycline is not allowed) • Hematopoietic growth factors, transfusions of blood or blood products within 1 week • Radiotherapy within 4 weeks • Major surgery within 4 weeks or planned major surgery during the study • NEOD001 at any time • Another investigational agent within 30 days 11. 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 12. History of Grade =3 infusion-associated adverse events (AEs) or hypersensitivity to another monoclonal antibody 13. Uncontrolled, active HIV, Hepatitis B, or Hepatitis C infection 14. Women who are lactating 15. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of NEOD001 in subjects with AL amyloidosis with hepatic involvement by assessing organ response.;Secondary Objective: ¿ To evaluate liver stiffness using elastogram ¿ To evaluate safety ¿ To evaluate general health-related quality of life using the Short Form-36 (SF-36) Health Survey ¿ To evaluate additional hepatic response rates ¿ To evaluate cardiac response rates in a subset of patients with cardiac involvement ¿ To evaluate renal response rates in a subset of patients with renal involvement ;Primary end point(s): Hepatic best response from Screening/Baseline to Month 6 defined as reduction in alkaline phosphatase of at least 50% or decrease in liver major diameter of at least 30% (by CT scan);Timepoint(s) of evaluation of this end point: month 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Liver elasticity as measured by elastogram at Months 6 and 12; Safety as assessed by vital signs, duration of therapy, 12 lead ECGs, routine laboratory assessments, and frequency and severity of AEs; Change from Screening/Baseline to Months 6, 9, and 12 in the SF-36 ; Hepatic best response from Screening/Baseline to Months 3, 9, and 12; For cardiac evaluable subjects: NT-proBNP best response from Baseline to Month 12 ; For renal evaluable subjects: proteinuria best response from Baseline to Month 12 ;Timepoint(s) of evaluation of this end point: months 6 and 12; At end of study; months 6, 9, and 12; months 3, 9, and 12; month 12; month 12 | — |
Countries
Italy
Contacts
Public ContactCentro per lo studio e la cura dell
Fondazione IRCCS Policlinico San Matteo
Outcome results
None listed