Renal AL Amyloid Involvement and NEOD001
Condition: Amyloidosis
MeSH terms: Amyloidosis
Intervention: NEOD001; Placebo
Intervention description: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates; Saline bag
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Amyloidosis; NEOD001; RAIN

Summary:

      This is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, two-arm,
      parallel-group efficacy and safety study of NEOD001 as a single agent administered
      intravenously in adults with AL amyloidosis who have a maintained hematologic response to
      their most recent treatment for AL amyloidosis (e.g., chemotherapy, autologous stem cell
      transplant [ASCT]) and have persistent renal dysfunction.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 18 years of age or older

          2. Biopsy-proven diagnosis of AL amyloidosis by immunohistochemistry or mass spectroscopy
             of a tissue biopsy excluding bone marrow

          3. Screening renal biopsy for RAIN confirming AL amyloidosis as exclusive or dominant
             cause of renal damage

          4. Persistent renal involvement from diagnosis with proteinuria (predominantly albumin) >
             500mg/day in a 24-hour urine collection

          5. CKD 1 to 3 (eGFR > 30)

          6. ≥1 prior systemic hematologic therapy for a free light chain (FLC) producing
             hematologic malignancy underlying the initial diagnosis of AL amyloidosis with at
             least a partial FLC response (PR, VGPR, CR) to treatment deemed stable and not
             requiring further treatment

          7. ECOG Performance Status ≤ 2

          8. Clinical laboratory values:

               1. Absolute neutrophil count > 1000/μL

               2. Platelet count > 75,000/μL

               3. Total bilirubin ≤ 1.5X ULN

               4. Alkaline phosphatase ≤ 5X ULN

               5. NT-proBNP < 1800 pg/mL

          9. Voluntary written consent must be given before performance of any study-related
             procedure not part of standard medical care with the understanding that consent may be
             withdrawn by the patient at any time without prejudice to future medical care

        Exclusion Criteria:

          1. Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL
             amyloidosis

          2. Female patients who are lactating, breastfeeding, or pregnant

          3. Patients who have not been treated or who have received chemotherapy within 6 months,
             or SCT within 12 months, for the light-chain producing hematologic disease causing AL
             amyloidosis, at the time of the first dose of NEOD001 (month 1 day 1)

          4. Patients who at initial diagnosis or later met the International Myeloma Working Group
             (IMWG) definition of active multiple myeloma requiring therapy (Appendix 3)

          5. Patients whose screening renal biopsies for RAIN show dominant causes of renal damage
             not related to AL amyloidosis

          6. Medically documented cardiac syncope, uncompensated congestive heart failure,
             myocardial infarction within the previous 6 months, unstable angina pectoris,
             clinically significant repetitive atrial or ventricular arrhythmias despite
             antiarrhythmic treatment, or severe orthostatic hypotension or clinically significant
             uncompensated autonomic insufficiency

          7. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          8. Ongoing or active infection, known HIV positive, known to be hepatitis B surface
             antigen-positive or has known or suspected active hepatitis C infection.

          9. Psychiatric illness/social situations that would limit compliance with study
             requirements