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Renal AL Amyloid Involvement and NEOD001 (RAIN)

Primary Purpose

Amyloidosis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
NEOD001
Placebo
Sponsored by
Tufts Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyloidosis focused on measuring Amyloidosis, NEOD001, RAIN

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care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

Sites / Locations

  • Mayo Clinic- Arizona
  • University of California San Francisco
  • Mayo Clinic- Florida
  • Tufts Medical Center
  • Karmanos Cancer Institute
  • Mayo Clinic- Minnesota
  • Memorial Sloan-Kettering Cancer Center
  • Hospital of the University of Pennsylvania
  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

NEOD001

Placebo

Arm Description

Study Drug given IV every 28 days at 24mg/kg

Placebo

Outcomes

Primary Outcome Measures

Confirmed Renal Response After Treatment With NEOD001
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

Measured GFR at Study Entry
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.
Time to CKD 4 or 5
Months to Chronic Kidney Disease level 4 or 5
Time to eGFR ≤ 15 or Dialysis
Months to estimated Glomerular Filtration Rate ≤ 15 or dialysis
Time to Doubling of Creatinine
Months to doubling of serum creatinine
Time to ≥ 40% Reduction in eGFR
Months to ≥ 40% reduction in estimated glomerular filtration rate
Renal Response in Patients With Maintained Hematologic Responses After 24 Monthly Treatments.
A renal response is a ≥ 30% decrease in proteinuria or drop of proteinuria below 0.5 g/24h in the absence of renal progression.
All Cause of Mortality at 26 Months
Death at 26 months from Baseline due to any cause

Full Information

First Posted
April 26, 2017
Last Updated
August 21, 2020
Sponsor
Tufts Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03168906
Brief Title
Renal AL Amyloid Involvement and NEOD001
Acronym
RAIN
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

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Terminated
Why Stopped
Futility
Study Start Date
July 5, 2017 (Actual)
Primary Completion Date
April 23, 2018 (Actual)
Study Completion Date
February 6, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tufts Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloidosis
Keywords
Amyloidosis, NEOD001, RAIN

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NEOD001
Arm Type
Experimental
Arm Description
Study Drug given IV every 28 days at 24mg/kg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
NEOD001
Intervention Description
NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Saline bag
Primary Outcome Measure Information:
Title
Confirmed Renal Response After Treatment With NEOD001
Description
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.
Time Frame
Baseline to 13 Months
Secondary Outcome Measure Information:
Title
Measured GFR at Study Entry
Description
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.
Time Frame
Baseline
Title
Time to CKD 4 or 5
Description
Months to Chronic Kidney Disease level 4 or 5
Time Frame
Baseline to 13 Months
Title
Time to eGFR ≤ 15 or Dialysis
Description
Months to estimated Glomerular Filtration Rate ≤ 15 or dialysis
Time Frame
Baseline to 13 Months
Title
Time to Doubling of Creatinine
Description
Months to doubling of serum creatinine
Time Frame
Baseline to 13 Months
Title
Time to ≥ 40% Reduction in eGFR
Description
Months to ≥ 40% reduction in estimated glomerular filtration rate
Time Frame
Baseline to 13 Months
Title
Renal Response in Patients With Maintained Hematologic Responses After 24 Monthly Treatments.
Description
A renal response is a ≥ 30% decrease in proteinuria or drop of proteinuria below 0.5 g/24h in the absence of renal progression.
Time Frame
Baseline to 26 months
Title
All Cause of Mortality at 26 Months
Description
Death at 26 months from Baseline due to any cause
Time Frame
Baseline to 26 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years of age or older Biopsy-proven diagnosis of AL amyloidosis by immunohistochemistry or mass spectroscopy of a tissue biopsy excluding bone marrow Screening renal biopsy for RAIN confirming AL amyloidosis as exclusive or dominant cause of renal damage Persistent renal involvement from diagnosis with proteinuria (predominantly albumin) > 500mg/day in a 24-hour urine collection CKD 1 to 3 (eGFR > 30) ≥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 ECOG Performance Status ≤ 2 Clinical laboratory values: Absolute neutrophil count > 1000/μL Platelet count > 75,000/μL Total bilirubin ≤ 1.5X ULN Alkaline phosphatase ≤ 5X ULN NT-proBNP < 1800 pg/mL 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: Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis Female patients who are lactating, breastfeeding, or pregnant 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) Patients who at initial diagnosis or later met the International Myeloma Working Group (IMWG) definition of active multiple myeloma requiring therapy (Appendix 3) Patients whose screening renal biopsies for RAIN show dominant causes of renal damage not related to AL amyloidosis 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 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 Ongoing or active infection, known HIV positive, known to be hepatitis B surface antigen-positive or has known or suspected active hepatitis C infection. Psychiatric illness/social situations that would limit compliance with study requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raymond Comenzo, MD
Organizational Affiliation
Tufts Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic- Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Mayo Clinic- Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic- Minnesota
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Renal AL Amyloid Involvement and NEOD001

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