Renal AL Amyloid Involvement and NEOD001

NCT03168906 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: NEOD001-RAIN
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 9

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.

Conditions

Amyloidosis

Keywords

Amyloidosis; NEOD001; RAIN

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 13 Months

Secondary Outcomes (7)

• Measured GFR at Study Entry

  Baseline

• Time to CKD 4 or 5

  Baseline to 13 Months

• Time to eGFR ≤ 15 or Dialysis

  Baseline to 13 Months

• Time to Doubling of Creatinine

  Baseline to 13 Months

• Time to ≥ 40% Reduction in eGFR

  Baseline to 13 Months

Study Arms (2)

NEOD001

EXPERIMENTAL

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

Drug: NEOD001

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

NEOD001 DRUG

NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates

NEOD001

Placebo DRUG

Saline bag

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tufts Medical Center: lead

Study Sites (9)

Mayo Clinic- Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Mayo Clinic- Florida

Jacksonville, Florida, 32224, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic- Minnesota

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Amyloidosis

Interventions

birtamimab

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Jaime Chisholm
• Organization: Tufts Medical Center

jchisholm1@tuftsmedicalcenter.org

617-636-5409

Study Officials

• Raymond Comenzo, MD

  Tufts Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 30, 2017
• Study Start: July 5, 2017
• Primary Completion: April 23, 2018
• Study Completion: February 6, 2019
• Last Updated: September 9, 2020
• Results First Posted: December 24, 2019

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)