NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000226-DK

Sponsoring Institute

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 75

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Primary Membranous Nephropathy;
Nephrotic Syndrome;
Pharmacokinetics (PK) Analysis;
Double-Blind (Masked), Placebo-Controlled Clinical Trial;
Co-administered belimumab and rituximab

Recruitment Keyword(s)

None

Condition(s)

Kidney Diseases;
Glomerulonephritis, Membranous;
Urologic Diseases;
Autoimmune Diseases;
Rituximab

Investigational Drug(s)

Belimumab
Rituximab

Investigational Device(s)

None

Intervention(s)

Drug: Rituximab
Drug: Belimumab
Other: Placebo

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

Background:

Primary membranous nephropathy (MN) causes the body s own immune system to damage the kidneys. This can cause the kidneys to fail. Researchers want to find new treatments for Primary MN that are better at improving the disease with fewer side effects.

Objective:

To learn if the combination of belimumab and rituximab is more effective in making and keeping Primary MN inactive than treatment with rituximab alone.

Eligibility:

People aged 18-75 with Primary MN.

Design:

Participants will be screened with a physical exam and blood and urine tests. They will collect their urine over a 24-hour period. They will have a medical history and cancer screening history. They may have a tuberculosis test.

Participants will be put into 2 groups. They will get either belimumab or placebo as a shot under the skin. They will get the shot once a week for 52 weeks. The participant, or another person, will be taught how to give the shot.

All participants will get rituximab intravenously at weeks 4 and 6. They will also get a drug to prevent pneumonia and other drugs to prevent side effects.

Participants will have study visits up to once a week for the first month, then at week 6, then once a month after that. At these visits, they will repeat some screening tests. They will have health assessments. They will complete quality of life and suicide risk surveys.

After treatment ends, participants will have follow-up visits every 3 months for 2 years. Participation will last for up to 3 years. Participants will have up to 27 study visits.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

Patients must meet all of the following criteria to be eligible for this study:

-Age 18 to 75 years inclusive

-Primary MN, confirmed with a kidney biopsy obtained in the past 36 months

-Anti-PLA^2R positive

-eGFR >= 40 mL/min/1.73m2 while on maximally tolerated RAS blockade

-Proteinuria:

-- >= 4 and < 8 g/day that has persisted for at least the previous 3 months while on maximally tolerated RAS blockade. Documentation of persistent proteinuria may be from a 24-hour collection or calculated from a spot urine collection. Or,

-- >= 8 g/day while on maximally tolerated RAS blockade

- Blood pressure while on maximally tolerated RAS blockade:

-- Systolic blood pressure <= 140 mmHg

-- Diastolic blood pressure <= 90 mmHg

EXCLUSION CRITERIA:

Patients who meet any of the following criteria will not be eligible for this study:

-Secondary cause of primary MN (e.g., SLE, drug, infection, malignancy) suggested by review of the patient 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 CR (Section 3.3.1) or PR (Section 3.3.2) 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, whichever 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 eGFR during the previous 3 months

- Decrease in proteinuria by 50% or more during the previous 12 months

- WBC count < 3.0 x 10^3/microliter

-. Absolute neutrophil count < 1.5 x 10^3/microliter

-. Moderately severe anemia (hemoglobin < 9 g/dL)

-. History of primary immunodeficiency

-. Serum IgA < 10 mg/dL

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 2x the upper limit of normal (ULN)

- Positive HIV serology

- Positive 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 positive HBsAg or positive HBcAb

- Positive QuantiFERON TB Gold test results. PPD tuberculin 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 except for 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 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 an anaphylactic reaction or known sensitivity or intolerance 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 and/or any suicidal ideation in the last 2 months, or who in the investigator's judgment, poses 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 or other clinically significant abnormal laboratory value which in the opinion of the investigator would put the patient at risk or confound the results of the study

- Inability to comply with study and follow-up procedures


--Back to Top--

Citations:

Not Provided

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Meryl A. Waldman, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)



Meryl A. Waldman, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10-CRC RM 5-5750
10 CENTER DR
BETHESDA MD 20814
(301) 451-6990
waldmanm@mail.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03949855

--Back to Top--