E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in subjects with AL amyloidosis who completed Study NEOD001 201 |
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E.1.1.1 | Medical condition in easily understood language |
Light chain (AL) amyloidosis is a blood disorder, which causes progressive organ damage as a result of the misfolding of proteins. This disease can produce a range of symptoms and organ dysfunction |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036673 |
E.1.2 | Term | Primary amyloidosis |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in subjects with AL amyloidosis who completed Study NEOD001 201 |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria (subjects must meet all of the following criteria): 1. Completed the EOS Visit in Study NEOD001-201 2. Adequate bone marrow reserve, hepatic and renal function, as demonstrated by: - Absolute neutrophil count (ANC) ≥1.0 × 109/L - Platelet count ≥75 × 109/L - Hemoglobin ≥9 g/dL - Total bilirubin ≤2 × upper limit of normal (ULN) - Aspartate aminotransferase (AST) ≤3 × ULN - Alanine aminotransferase (ALT) ≤3 × ULN - Alkaline phosphatase (ALP) ≤5 × ULN (except for subjects with hepatomegaly and isozymes specific to liver, rather than bone) - Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, or measured GFR ≥25 mL/min/1.73 m2 3. Systolic blood pressure 80-180 mmHg 4. Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective physician-approved contraception (Appendix 2) from Screening to 90 days following the last study drug administration 5. Male subjects must be surgically sterile or must agree to use highly effective physician-approved contraception (Appendix 2) from Screening to 90 days following the last study drug administration 6. Ability to understand and willingness to sign an informed consent form (ICF) prior to initiation of any study procedures |
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E.4 | Principal exclusion criteria |
Exclusion Criteria (subjects must not meet any of the following criteria): 1. Any new medical contraindication or clinically significant abnormality on physical, neurological, laboratory, vital signs, or electrocardiographic (ECG) examination (e.g., atrial fibrillation; with the exception of subjects for whom the ventricular rate is controlled) that precludes continuation or initiation of treatment with NEOD001 or participation in the study 2. 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 3. Myocardial infarction, uncontrolled angina, uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit 4. Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease 5. ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following: - First degree atrioventricular (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 (uncontrolled [i.e., >110 bpm] ventricular rate is not allowed [determined by an average of three beats in Lead II or 3 representative beats if Lead II is not representative of the overall ECG]) 6. Has not recovered (i.e., equivalent to a Common Terminology Criteria for Adverse Events [CTCAE] ≥Grade 2) from the clinically significant toxic effects of prior anticancer therapy. Exception: subjects who have received treatment with a proteasome inhibitor such as bortezomib may have CTCAE Grade 2 neuropathy. 7. Received any of the following within the specified time frame prior to the Month 1-Day 1 Visit: - Oral or IV antibiotics, antifungals, or antivirals within 1 week, with the exception of prophylactic oral agents. Note: In the event that a subject requires the chronic use of antivirals, Medical Monitor permission is required for entry into the study. - Hematopoietic growth factors, transfusions of blood or blood products within 1 week - Chemotherapy, radiotherapy, HDAC inhibitors, or other plasma cell directed therapy within 2 weeks - ASCT within 4 weeks (i.e., ASCT is allowed if it occurred before enrollment in Study NEOD001-201 or after completion of Study NEOD001-201 if it was at least 4 weeks before Month 1-Day 1 of this study) - Major surgery within 4 weeks (or within 2 weeks following consultation with and approval of Medical Monitor) - Planned organ transplant during the study - Any investigational agent, other than NEOD001, within 4 weeks - Any experimental imaging agent directed at amyloid within 2 weeks 8. 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 - Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 mg/mL - Any other cancer from which the subject has been disease-free for ≥2 years 9. History of Grade ≥3 infusion-related adverse events (AEs) or hypersensitivity to NEOD001 10. History of severe allergy to any of the components of NEOD001 such as histidine/L-Histidine, Trehalose, or Polysorbate 20 11. Currently known uncontrolled bacterial, viral, fungal, HIV, hepatitis B, or hepatitis C infection 12. Women who are breastfeeding 13. 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 14. Unable or unwilling to adhere to the study-specified procedures and restrictions 15. Subject is under legal custodianship |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Endpoints: • Long-term safety and tolerability as assessed by vital signs, 12 lead ECGs, routine clinical laboratory assessments, and AEs • Immunogenicity
Efficacy Endpoints: • N-terminal pro-brain natriuretic peptide (NT-proBNP): - Response (Appendix 3) - Best response from baseline - Change from baseline • Change from baseline in troponin T • Change from baseline in the Short Form-36 Health Survey version 2 (SF-36v2) Physical Component Score (PCS), Mental Component Score (MCS), and the 8 subscales • Change from baseline in the 6-Minute Walk Test (6MWT) distance (meters) • Progression-free survival • For renal-evaluable subjects: - Renal response (Appendix 3) - Renal best response from baseline - Change from baseline in creatinine, proteinuria, and eGFR - Time to eGFR: - ≤15 mL/min/1.73 m2 (Chronic Kidney Disease [CKD] Stage 5) - <30 mL/min/1.73 m2 (CKD Stage 4) - <60 mL/min/1.73 m2 (CKD Stage 3) - Time to any worsening in CKD Stage - Time to 40% reduction in eGFR - Time to doubling of creatinine • For peripheral neuropathy-evaluable subjects: - Change from baseline in Neuropathy Impairment Score–Lower Limbs (NIS-LL) total score - Peripheral neuropathy best response - Peripheral neuropathy response (Appendix 3) - For subjects with painful peripheral neuropathy in Study NEOD001-201 (i.e., baseline Visual Analog Scale – Pain Intensity [VASPI] score >0) change from baseline in the VASPI score • For hepatic-evaluable subjects: - Hepatic response (Appendix 3) - Hepatic best response from baseline • Time to all-cause mortality (overall survival) • Frequency and duration of hospitalizations over the course of the study • Change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) subscores and overall summary score • Time to progression for each organ (cardiac/NT-proBNP, renal, peripheral neuropathy, hepatic) separately and to any organ progression • Eastern Cooperative Oncology Group (ECOG) Performance Status and New York Heart Association (NYHA) Class at each visit including any changes from baseline • Change from baseline in serum free light chains (sFLCs), serum and 24-hour urine protein electrophoresis (PEP), and serum and urine immunofixation electrophoresis (IFE) • Severity of disease-related symptoms including any changes from baseline • Pharmacokinetics (PK) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 38 months or until the study is terminated. Refer to Study Protocol, Table 1 Schedule of Assessments. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
France |
Germany |
Greece |
Israel |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study is expected to be completed approximately 3 years after the last subject is enrolled. The study is considered completed with the last assessment for the last subject participating in the study or if the study is terminated, whichever occurs first. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |