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Efficacy of Belimumab and Rituximab Compared to Rituximab Alone for the Treatment of Primary Membranous Nephropathy

Completed

This trial is a two-part study (Part A and Part B) of adults with primary membranous nephropathy, ages 18-75 inclusive. Part A is an open-label, PK phase to compare belimumab exposure between participants who have “low” proteinuria (≥ 4 to < 8 g/day) and “high” proteinuria (≥ 8 g/day) at Visit -1. Part B is a prospective, randomized, phase II, double-blind, placebo-controlled, multicenter clinical trial in adults with primary MN. Part B will commence after the analysis of the PK data in Part A.

I'm interested

All
18 Years to 75 Years old
This study is NOT accepting healthy volunteers
Inclusion Criteria:
Subjects must meet all of the following criteria to be eligible for this study-
• Diagnosis of one of the following:
• Primary membranous nephropathy (MN):
• Confirmed by kidney biopsy obtained in the past 5 years, or
• If relapsing following a complete remission or partial remission, confirmed with a kidney biopsy obtained in the past 7 years
• Nephrotic syndrome, and a contraindication to kidney biopsy (e.g., anti-coagulation, solitary kidney, body habitus that increases the risk of biopsy, or other contraindication in the opinion of the investigator).
• Serum anti-PLA2R positive;
• Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min/1.73m^2 while on maximally tolerated renin-angiotensin system (RAS) blockade;
• Proteinuria:
• ≥4 and < 8 g/day that has been present for ≥ 3 months while on while on maximally tolerated RAS blockade, or
• ≥8 g/day while on maximally tolerated RAS blockade.
• Blood pressure while on maximally tolerated RAS blockade:
• Systolic blood pressure ≤ 140 mmHg, and
• Diastolic blood pressure ≤ 90 mmHg
Exclusion Criteria:
Subjects meeting any of the following criteria will not be eligible for this study-
• Secondary cause of membranous nephropathy (MN) (e.g., systemic lupus erythematosus (SLE), drug, infection, malignancy) suggested by review of the subject's medical history and/or clinical presentation;
• Rituximab use within the previous 12 months;
• Rituximab use > 12 months ago:
• With an undetectable CD19 B cell count, or
• Did not result in a complete remission (CR) or partial remission (PR) with rituximab treatment alone (e.g., without other immunosuppressive or immunomodulatory therapy).
• Use of anti-B cell therapy other than rituximab within the previous 12 months (or 5 half-lives, whichever is greater);
• Cyclophosphamide use within the past 3 months;
• Use of other immunosuppressive medications, such as cyclosporine or tacrolimus, within the past 30 days;
• Use of systemic corticosteroids within the past 30 days;
• Use of any biologic investigational agent, defined as any drug not approved for sale in the country it is used, in the previous 12 months;
• Use of any non-biologic investigational agent in the past 30 days (or 5 half-lives, which ever is greater);
• Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥ 9.0%
• Patients with diabetic glomerulopathy on renal biopsy that is:
• Greater than Class I diabetic glomerulopathy, or
• Class I diabetic glomerulopathy with a history of poor diabetic control (e.g., HbA1c ≥ 9.0%) since time of biopsy;
• Unstable kidney function defined as > 15% decrease in the Estimated Glomerular Filtration Rate (eGFR) during the previous 3 months;
• Decrease in proteinuria by 50% or more during the previous 12 months;
• White blood cell (WBC) count < 3.0 x 10^3/µl;
• Absolute neutrophil count < 1.5 x 10^3/µl;
• Moderately severe anemia (hemoglobin <9mg/dL);
• History of primary immunodeficiency;
• Serum immunoglobulin A (IgA) < 10 mg/dL;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = ≥2 times the upper limit of normal (ULN);
• Positive human immunodeficiency virus (HIV) serology;
• Positive hepatitis C virus (HCV) serology, unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load 24 weeks after cessation of therapy);
• Evidence of current or prior infection with hepatitis B, as indicated by a positive HBsAg, positive HBcAb, or positive HBsAb serology without history of vaccination;
• Positive QuantiFERON - tuberculosis (TB) Gold test results, --Note: Tuberculin Purified Protein Derivative (PPD) test may be substituted for QuantiFERON - TB Gold test.
• History of lung disease with FVC < 70% predicted, DLCO < 70% predicted, or requiring supplemental oxygen;
• History of malignant neoplasm within the last 5 years, --Exception: basal cell or squamous cell carcinoma of the skin treated with local resection only, or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years.
• Absence of individualized, age-appropriate cancer screening;
• Women of child-bearing potential who are pregnant, nursing, or unwilling to be sexually inactive or use FDA-approved contraception until study week 104;
• Acute or chronic infection, including:
• current use of suppressive therapy for chronic infection,
• hospitalization for treatment of infection in the past 60 days, or
• parenteral anti-microbial (including anti-bacterial, anti-viral, or anti-fungal agents) use in the past 60 days for infection.
• History of anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies, including:
• rituximab, or
• belimumab.
• Evidence of serious suicide risk, including:
• any history of suicidal behavior in the last 6 months,
• any suicidal ideation in the last 2 months, or
• who, in the investigator's judgment, pose a significant suicide risk.
• Evidence of current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence in the past 12 months;
• Vaccination with a live vaccine within the past 30 days;
• Other diseases or conditions which, in the opinion of the investigator, would put the subject at risk or confound the results of the study; or
• Inability to comply with study and follow-up procedures.

Drug: Belimumab, Drug: Placebo for Belimumab, Drug: Rituximab

Membranous Nephropathy, Nephrotic Syndrome

Primary Membranous Nephropathy, nephrotic syndrome, Pharmacokinetics (PK) Analysis, Double-Blind (Masked), Placebo-Controlled Clinical Trial, Co-administered belimumab and rituximab, Clinics and Surgery Center (CSC)

Patrick Nachman - pnachman@umn.edu
Patrick Nachman
Phase 2
STUDY00006831
NCT03949855
See this study on ClinicalTrials.gov

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