A Single Arm, Multicenter, Phase II, Open-Label Trial to Evaluate Efficacy of Isatuximab in Patients With Monoclonal Gammopathy of Renal Significance

The purpose of this study is to see whether Isatuximab can help improve kidney function of participants with MGRS To evaluate the efficacy and safety of Isatuximab, an anti-CD38 monoclonal antibody, in patients with PNGMID or C3 glomerulopathy. Response assessment was based on change in proteinuria and serum creatinine with complete response defined as drop in proteinuria below 500 mg/day and partial response defined as ≥ 50% drop in 24-hr urine protein with stable creatinine (within 25% of baseline). To evaluate the efficacy and safety of Isatuximab, an anti-CD38 monoclonal antibody, in patients with PGNMID or C3 glomerulopathy. Here, we report the outcomes of the patients (N=12) who have been treated in the clinical trial. Response assessment was based on changes in proteinuria and serum creatinine. A complete response was defined as a drop in proteinuria below 500 mg/day, and a partial response was defined as a ≥50% reduction in 24-hour urine protein with stable creatinine (within 25% of baseline)

CT.gov Identifier

NCT04614558

EudraCT Identifier

N/A

CTIS:

N/A

Collaborator

Columbia University Medical Center

Study Contact Information

+ 33 1 53 77 40 00

Recruiting

Study Details

Diseases

Glomerulonephritis and atypical hemolytic uremic syndrome (aHUS)

Atypical Hemolytic Uremic Syndrome; C3 Glomerulopathy; Complement Factor H Deficiency

Study Drug

Isatuximab (intravenous)

Genes

CFI

CFH

Study Dates

Jun 2021 - Apr 2026

Sex

Female & Male

Age

18+ years

Inclusion and Exclusion Criteria

Inclusion Criteria:

1. Renal biopsy proven diagnosis of an MGRS disorder including the following:
1. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)
2. C3 glomerulopathy associated with monoclonal gammopathy
3. Non-Amyloid Fibrillary Glomerulonephritis
4. Light chain Proximal Tubulopathy
5. 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.
2. Measurable Proteinuria ≥1gram over 24 hours.
3. 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.
4. Age ≥18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
6. Life expectancy of greater than 6 months
7. Participants must have normal organ and marrow function as defined below:
Leukocytes ≥3,000/microliters (mcL)
1. absolute neutrophil count ≥1,500/mcL
2. platelets ≥100,000/mcL
3. total bilirubin within normal institutional limits
4. Aspartate aminotransferase (AST) (SGOT)/alanine transaminase (ALT)(SGPT) ≤2.5 ×
institutional upper limit of normal
5. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2.
Patients with newly-diagnosed or previously treated PGNMID or C3 glomerulopathy with monoclonal gammopathy who had ≥1 g of proteinuria on 24 hour collection and estimated glomerular filtration rate (eGFR) ≥30 mL/min were eligible.

Exclusion Criteria:

1. 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 2. Participants who are receiving any other investigational agents concurrently. 3. History of severe allergic reactions or anaphylaxis attributed to compounds of similar chemical or biologic composition to Isatuximab. 4. Diagnosis of Multiple Myeloma or High risk smoldering Multiple Myeloma or a B cell lymphoma meeting criteria for therapy. 5. Renal Biopsy showing the coexistence of other significant diagnosis e.g. diabetic nephropathy. 6. 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. 7. 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. 8. HIV-positive Participants are ineligible because of increased risk of lethal infections when treated with immunosuppressive therapy. Prior treatment with anti-CD38 antibody was an exclusion criteria.

Protocol Summary

Study Locations

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