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Renal AL Amyloid Involvement and NEOD001 (RAIN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03168906
Recruitment Status : Terminated (Futility)
First Posted : May 30, 2017
Results First Posted : December 24, 2019
Last Update Posted : September 9, 2020
Information provided by (Responsible Party):
Tufts Medical Center

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.

Condition or disease Intervention/treatment Phase
Amyloidosis Drug: NEOD001 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : July 5, 2017
Actual Primary Completion Date : April 23, 2018
Actual Study Completion Date : February 6, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis

Arm Intervention/treatment
Experimental: NEOD001
Study Drug given IV every 28 days at 24mg/kg
Drug: NEOD001
NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates

Placebo Comparator: Placebo
Drug: Placebo
Saline bag

Primary Outcome Measures :
  1. Confirmed Renal Response After Treatment With NEOD001 [ Time Frame: Baseline to 13 Months ]
    A renal response is a ≥ 30% reduction in proteinuria in the absence of a ≥ 25% decrease in eGFR. A confirmed renal response is one that has been documented as present one month after 12 monthly treatments.

Secondary Outcome Measures :
  1. Measured GFR at Study Entry [ Time Frame: Baseline ]
    The aim of this study is to assess the performance of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine in comparison to iothalamate clearance measured in AL amyloidosis patients. Iothalamate will be given subcutaneously. Urine and plasma samples will then be obtained. All laboratory tests for samples obtained for GFR measurement will be performed at Mayo Clinic Rochester. Quantification of iothalamate in urine and plasma will be performed using a tandem mass spectrometric method.

  2. Time to CKD 4 or 5 [ Time Frame: Baseline to 13 Months ]
    Months to Chronic Kidney Disease level 4 or 5

  3. Time to eGFR ≤ 15 or Dialysis [ Time Frame: Baseline to 13 Months ]
    Months to estimated Glomerular Filtration Rate ≤ 15 or dialysis

  4. Time to Doubling of Creatinine [ Time Frame: Baseline to 13 Months ]
    Months to doubling of serum creatinine

  5. Time to ≥ 40% Reduction in eGFR [ Time Frame: Baseline to 13 Months ]
    Months to ≥ 40% reduction in estimated glomerular filtration rate

  6. Renal Response in Patients With Maintained Hematologic Responses After 24 Monthly Treatments. [ Time Frame: Baseline to 26 months ]
    A renal response is a ≥ 30% decrease in proteinuria or drop of proteinuria below 0.5 g/24h in the absence of renal progression.

  7. All Cause of Mortality at 26 Months [ Time Frame: Baseline to 26 months ]
    Death at 26 months from Baseline due to any cause

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03168906

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United States, Arizona
Mayo Clinic- Arizona
Scottsdale, Arizona, United States, 85259
United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, Florida
Mayo Clinic- Florida
Jacksonville, Florida, United States, 32224
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic- Minnesota
Rochester, Minnesota, United States, 55905
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Tufts Medical Center
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Study Chair: Raymond Comenzo, MD Tufts Medical Center
  Study Documents (Full-Text)

Documents provided by Tufts Medical Center:
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Responsible Party: Tufts Medical Center Identifier: NCT03168906    
Other Study ID Numbers: NEOD001-RAIN
First Posted: May 30, 2017    Key Record Dates
Results First Posted: December 24, 2019
Last Update Posted: September 9, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tufts Medical Center:
Additional relevant MeSH terms:
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Proteostasis Deficiencies
Metabolic Diseases