Isatuximab in Patients With Monoclonal Gammopathy of Renal Significance

NCT04614558 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAT0761
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to see whether Isatuximab can help improve kidney function of participants with MGRS. Isatuximab is approved by the Food and Drug Administration (FDA) for the treatment of adult patients with multiple myeloma, but it is not approved by the FDA to treat MGRS. This means that the use of isatuximab in this study is considered 'investigational'.

Conditions

Monoclonal Gammopathy

Outcome Measures

Primary Outcomes (1)

• Overall Renal Response Rate

  Renal response defined as a decrease in 24-hour proteinuria by \>50% at any point post therapy.

  Up to 6 months

Secondary Outcomes (2)

• Number of Adverse Events

  Up to 12 months

• Percentage of Participants with Immunoglobulin Gene Mutations

  Baseline, up to 4 weeks prior to treatment

Study Arms (1)

Isatuximab for MGRS

EXPERIMENTAL

Subjects will receive Isatuximab for 6 months and will be followed for an additional one year post therapy for outcome follow-up.

Drug: Isatuximab

Interventions

Isatuximab DRUG

Isatuximab in IV form (10mg/kg q weekly x 4 doses followed by 10mg/kg q 2 weeks) for a total of 6 month duration. Doses should be initiated at 175 mg/hour up to a maximum of 400 mg/hour. Isatuximab (SAR) is monoclonal antibody (mAb).

Also known as: Sarclisa

Isatuximab for MGRS

Eligibility Criteria

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

You may qualify if:

• Renal biopsy proven diagnosis of an MGRS disorder including the following:
• Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)
• C3 glomerulopathy associated with monoclonal gammopathy
• Non-Amyloid Fibrillary Glomerulonephritis
• Light chain Proximal Tubulopathy
• Immunotactoid Glomerulopathy
• A concurrent diagnosis of Monoclonal gammopathy (with +ve Serum and/or Urine protein electrophoresis or Bone marrow biopsy) is required in patients with C3 glomerulopathy but not for other disorders. Patients with concurrent MGUS, non-high risk smoldering myeloma are eligible for enrollment.
• Measurable Proteinuria ≥1gram over 24 hours.
• Prior Therapy: Newly diagnosed as well as patients with previous therapy but persistent renal dysfunction and persistent proteinuria ≥1gram over 24 hours are eligible for enrollment. Patients who received a prior cluster of differentiation 38 (CD38) antibody therapy are not eligible for study. In patients who have received prior therapy a wash out period of 12 weeks for chemotherapy based therapies and 24 weeks for Rituximab based therapies is required between completion of prior therapy and cycle 1 Day1 of study therapy.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Life expectancy of greater than 6 months
• Participants must have normal organ and marrow function as defined below:
• Leukocytes ≥3,000/microliters (mcL)
• absolute neutrophil count ≥1,500/mcL

You may not qualify if:

• Participants who have had chemotherapy based therapy within 12 weeks or Rituximab based therapy within prior 24 weeks prior to starting the cycle 1 Day 1 of trial therapy
• Participants who are receiving any other investigational agents concurrently.
• History of severe allergic reactions or anaphylaxis attributed to compounds of similar chemical or biologic composition to Isatuximab.
• Diagnosis of Multiple Myeloma or High risk smoldering Multiple Myeloma or a B cell lymphoma meeting criteria for therapy.
• Renal Biopsy showing the coexistence of other significant diagnosis e.g. diabetic nephropathy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and Lactating women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Isatuximab.
• HIV-positive Participants are ineligible because of increased risk of lethal infections when treated with immunosuppressive therapy.

Sponsors & Collaborators

• Columbia University: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (2)

Massachusetts General Hospital, Renal Associates Clinic

Boston, Massachusetts, 02114, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Paraproteinemias

Interventions

isatuximab

Condition Hierarchy (Ancestors)

Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Divaya Bhutani, MD

  Assistant Professor of Medicine at the Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: The study will be a single arm, prospective, multi-center, phase II, open- label study including 27 subjects in total. The study will consist of a screening phase, treatment phase, post-treatment observation phase and follow-up phase

Study Record Dates

• First Submitted: October 29, 2020
• First Posted: November 4, 2020
• Study Start: June 8, 2021
• Primary Completion: October 23, 2025
• Study Completion (Estimated): February 1, 2027
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)