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Trial record 1 of 1 for:    RAIN | Recruiting, Not yet recruiting Studies | amyloidosis | United States
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Renal AL Amyloid Involvement and NEOD001 (RAIN)

This study is currently recruiting participants.
Verified July 2017 by Tufts Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT03168906
First Posted: May 30, 2017
Last Update Posted: July 17, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Tufts Medical Center
  Purpose
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 Intervention Phase
Amyloidosis Drug: NEOD001 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • 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:
  • 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.

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

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

  • Time to doubling of Creatinine [ Time Frame: Baseline to 13 Months ]
    Months to doubling of serum creatinine

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

  • 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.

  • All cause of mortality at 26 months [ Time Frame: Baseline to 26 months ]
    Death at 26 months from Baseline due to any cause


Estimated Enrollment: 100
Actual Study Start Date: July 5, 2017
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo
Drug: Placebo
Saline bag

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

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT03168906


Contacts
Contact: Corey Michelson 617-636-7388 cmichelson@tuftsmedicalcenter.org
Contact: Emmanuel Larbi 617-636-2616 elarbi@tuftsmedicalcenter.org

Locations
United States, Arizona
Mayo Clinic- Arizona Not yet recruiting
Scottsdale, Arizona, United States, 85259
Contact: Joseph Mikhael, MD         
United States, California
University of California San Francisco Not yet recruiting
San Francisco, California, United States, 94143
Contact: Sandy Wong, MD         
United States, Florida
Mayo Clinic- Florida Not yet recruiting
Jacksonville, Florida, United States, 32224
Contact: Taimur Sher, MD         
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Cindy Varga, MD         
United States, Michigan
Karmanos Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Jeff Zonder, MD         
United States, Minnesota
Mayo Clinic- Minnesota Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Morie Gertz, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Heather Landau, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Brendan Weiss, MD         
United States, Tennessee
Vanderbilt University Medical Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Stacey Goodman, MD         
Sponsors and Collaborators
Tufts Medical Center
Investigators
Study Chair: Raymond Comenzo, MD Tufts Medical Center
  More Information

Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT03168906     History of Changes
Other Study ID Numbers: NEOD001-RAIN
First Submitted: April 26, 2017
First Posted: May 30, 2017
Last Update Posted: July 17, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tufts Medical Center:
Amyloidosis
NEOD001
RAIN

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases