Clinical trial NCT03168906: Renal AL Amyloid Involvement and NEOD001
Official title: The RAIN Study, a Multicenter Randomized Double-blind Phase 2b Study of NEOD001 in Previously Treated Subjects With Systemic Light-chain (AL) Amyloidosis and Persistent Renal Involvement
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Amyloidosis
Keywords: Amyloidosis
NEOD001
RAIN
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
First posted: 2017-05-30
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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 \[SCT\]) and have persistent renal dysfunction. Subject screening will occur during the 28 days prior to the first administration of study drug (i.e. month 1 day 1). If screening assessments are completed and all eligibility requirements are met, the subject will be enrolled. Study visits will occur every 28 days based on scheduling from month 1 day 1. A ±5-day window is allowed for visits starting after month 1. Subjects may receive up to 12 infusions of study drug. Subjects who discontinue study drug before the initial End of Study (EOS) visit should have an Early Treatment Discontinuation (ETD) Visit 30 (±5) days after their final administration of study drug. After completing 12 months of treatment and the confirmatory EOS visit, a subject may enter an open-label extension (OLE) study, during which subjects will receive active treatment with NEOD001 for 12 months and may receive concurrent chemotherapy.

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

Primary outcomes:
measure: Confirmed Renal Response After Treatment With NEOD001
timeFrame: Baseline to 13 Months
Secondary outcomes:
measure: Measured GFR at Study Entry
timeFrame: Baseline
measure: Time to CKD 4 or 5
timeFrame: Baseline to 13 Months
measure: Time to eGFR ≤ 15 or Dialysis
timeFrame: Baseline to 13 Months
measure: Time to Doubling of Creatinine
timeFrame: Baseline to 13 Months
measure: Time to ≥ 40% Reduction in eGFR
timeFrame: Baseline to 13 Months
measure: Renal Response in Patients With Maintained Hematologic Responses After 24 Monthly Treatments.
timeFrame: Baseline to 26 months
measure: All Cause of Mortality at 26 Months
timeFrame: Baseline to 26 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic- Arizona
state: Arizona
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic- Florida
state: Florida
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic- Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Tufts Medical Center
name: Raymond Comenzo, MD
role: STUDY_CHAIR
References: