Belimumab With Rituximab for Primary Membranous Nephropathy

• Register: ClinicalTrials.gov
• Last refreshed on: 15 April 2024
• Main ID: NCT03949855
• Date of registration: 13/05/2019
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Belimumab With Rituximab for Primary Membranous Nephropathy REBOOT
• Scientific title: Efficacy of Belimumab and Rituximab Compared to Rituximab Alone for the Treatment of Primary Membranous Nephropathy (ITN080AI)
• Date of first enrolment: March 6, 2020
• Target sample size: 124
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03949855
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Canada, United States

Contacts

• Name: Iñaki Sanz, M.D.
• Affiliation: Emory University, Department of Medicine, Division of Rheumatology

• Name: Patrick Nachman, M.D.
• Affiliation: University of Minnesota, Department of Medicine, Division of Renal Diseases and Hypertension

Key inclusion & exclusion criteria

Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for this study-

1. Age 18 to 75 years inclusive

2. Diagnosis of one of the following:

1. Primary MN confirmed by a kidney biopsy within the past 5 years

2. Primary MN that is relapsing following a CR (Section 3.3.1) or PR (Section
3.3.2), confirmed by a kidney biopsy within the past 7 years

3. Nephrotic syndrome with eGFR > 60 mL/min/1.73m2 and no history of
immunosuppressant treatment (e.g. glucocorticoids, cyclophosphamide, cyclosporine
A, tacrolimus, B-cell depleting agent) for nephrotic syndrome, and without
evidence of a secondary cause of nephrotic syndrome

4. Nephrotic syndrome and a contraindication to kidney biopsy (e.g.,
anticoagulation, solitary kidney, body habitus that increases the risk of biopsy,
or other contraindication in the opinion of the investigator), and without
evidence of a secondary cause of nephrotic syndrome

3. Serum anti-PLA2R positive

4. eGFR = 30 mL/min/1.73m2 while on maximally tolerated RAS blockade

5. Proteinuria:

1. = 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,

2. = 8 g/day while on maximally tolerated RAS blockade

6. Blood pressure while on maximally tolerated RAS blockade:

1. Systolic blood pressure = 140 mmHg

2. Diastolic blood pressure = 90 mmHg

7. SARS-CoV-2 vaccination according to the current Centers for Disease Control and
Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations.
The last SARS-CoV-2 vaccine dose must have been administered at least 14 days prior
the initiation of the study drug (Visit 0).

Exclusion Criteria:

Subjects meeting any of the following criteria will not be eligible for this study-

1. Secondary cause of MN (e.g., SLE, drug, infection, malignancy) suggested by review of
the patient's medical history and/or clinical presentation

2. Rituximab use within the previous 12 months

3. Rituximab use > 12 months ago:

1. With an undetectable CD19 B cell count, or

2. 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)

4. Use of anti-B cell therapy other than rituximab within the previous 12 months (or 5
half-lives, whichever is greater)

5. Cyclophosphamide use within the past 3 months

6. Use of other immunosuppressive medications such as cyclosporine or tacrolimus within
the past 30 days

7. Use of systemic corticosteroids within the past 30 days

8. 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

9. Use of any non-biologic investigational agent in the past 30 days (or 5 half-lives,
whichever is greater)

10. Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) = 9.0%

11. Patients with diabetic glomerulopathy on renal biopsy that is:

1. Greater than Class I diabetic glomerulopathy, or

2. Class I diabetic glomerulopathy with a history of poor diabetic control (e.g.,
HbA1c = 9.0%) since time of biopsy

12. Unstable kidney function defined as > 20% decrease in eGFR during the previous 3
months due to primary MN, as determined by the site investigator in consultation with
the protocol chair

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

14. WBC count < 3.0 x 103/µl

15. Absolute neutrophil count < 1.5 x 103/µl

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

17. History of primary immunodeficiency

18. Serum IgA < 10 mg/dL

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

20. Positive HIV serology

21. 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)

22. Evidence of current or prior infection with hepatitis B, as indicated by positive
HBsAg or positive HBcAb

23. Positive QuantiFERON - TB Gold test results. PPD tuberculin test may be substituted
for QuantiFERON - TB Gold test

24. History of lung disease with FVC < 70% predicted, DLCO < 70% predicted, or requiring
supplemental oxygen

25. 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

26. Absence of individualized, age-appropriate cancer screening

27. Women of child-bearing potential who are pregnant, nursing, or unwilling to be
sexually inactive or use FDA-approved contraception until week 104

28. 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

29. 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

30. 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

31. Evidence of current drug or alcohol abuse or dependence, or a history of drug or
alcohol abuse or dependence in the past 12 months

32. Vaccination with a live vaccine within the past 30 days

33. 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

34. Inability to comply with study and follow-up procedures



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Membranous Nephropathy

Nephrotic Syndrome

Intervention(s)

Drug: Rituximab

Drug: Belimumab

Drug: Placebo for Belimumab

Primary Outcome(s)

Proportion of Participants in Complete Remission (CR) at Week 104: By Treatment Group [Time Frame: Week 104]

Secondary Outcome(s)

Proportion of participants meeting criteria for a second course of rituximab at week 30 [Time Frame: Week 30]

Incidence of Venous Thromboembolic Events: By Treatment Group [Time Frame: Week 0 to Week 52]

Kidney Disease Quality of Life (KDQOL-36) Mean Scale Scores at Baseline, Week 52, Week 104 and Week 156: By Treatment Group [Time Frame: Week 52, Week 104, Week 156]

Incidence of Grade 3 or Higher Infectious Adverse Events (AEs): By Treatment Group [Time Frame: Week 0 to Week 52]

Proportion of Participants in Complete Remission (CR) and Anti-PLA2R Negative: By Treatment Group [Time Frame: Week 104]

Proportion of Participants in Complete Remission (CR) at Week 52 and Week 156: By Treatment Group [Time Frame: Week 52, Week 156]

Proportion of Participants in Partial Remission (PR) and Anti-PLA2R Negative: By Treatment Group [Time Frame: Week 104]

Proportion of Participants in Partial Remission (PR) at Week 52, Week 104 and Week 156: By Treatment Group [Time Frame: Week 52, Week 104, Week 156]

Incidence of Adverse Events (AEs): By Treatment Group [Time Frame: Week 0 to Week 52]

Proportion of Participants in Complete or Partial Remission at Week 52, Week 104, Week 156: By Treatment Group [Time Frame: Week 52, Week 104, Week 156]

Time to Relapse for Participants who Achieved Complete Remission (CR) or Partial Remission (PR): By Treatment Group [Time Frame: Up to 156 Weeks (3 Years)]

Proportion of Participants Who are Anti-PLA2R Negative: By Treatment Group [Time Frame: Week 52, Week104, Week 156]

Belimumab Exposure After the First 4 Doses of Belimumab [Time Frame: Week 0, Week 1, Week 2, Week 3]

Incidence of Arterial Thromboembolic Events: By Treatment Group [Time Frame: Week 0 to Week 52]

Level of Proteinuria at Week 52, Week 104 and Week 156: By Treatment Group [Time Frame: Week 52, Week 104, Week 156]

Secondary ID(s)

NIAID CRMS ID#:38478

DAIT ITN080AI

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline

Immune Tolerance Network (ITN)

PPD

Rho Federal Systems Division, Inc.