Study in Subjects With Light Chain (AL) Amyloidosis
Condition: AL Amyloidosis
MeSH terms: Immunoglobulin Light-chain Amyloidosis; Amyloidosis
Intervention: NEOD001
Intervention description: humanized monoclonal antibody
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in
      subjects with AL amyloidosis who have completed Study NEOD001-201.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Completed the End of Study 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 must have a negative pregnancy test during Screening
             and must agree to use highly effective physician-approved contraception 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 from Screening to 90 days following the last study
             drug administration

          6. Ability to understand and willingness to sign an informed consent form prior to
             initiation of any study procedures

        Exclusion 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