Renal AL Amyloid Involvement and NEOD001

NCT ID: NCT03168906

Last Updated: 2020-09-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-05
• Study Completion Date: 2019-02-06

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.

Conditions

Amyloidosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NEOD001

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

Group Type: EXPERIMENTAL

NEOD001

Intervention Type: DRUG

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

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Saline bag

Interventions

NEOD001

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

Intervention Type: DRUG

Placebo

Saline bag

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tufts Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raymond Comenzo, MD

Role: STUDY_CHAIR

Tufts Medical Center

Locations

Mayo Clinic- Arizona

Scottsdale, Arizona, United States

University of California San Francisco

San Francisco, California, United States

Mayo Clinic- Florida

Jacksonville, Florida, United States

Tufts Medical Center

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic- Minnesota

Rochester, Minnesota, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NEOD001-RAIN

Identifier Type: -

Identifier Source: org_study_id