Obinutuzumab Induced Decreases of PLA2R Antibodies in Membranous Nephropathy: a Pilot Study

NCT07163611 | Recruiting Phase 2

• 1 other identifier: 2025-521139-35-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To assess the disappearance rate (half-life) of anti-PLA2R antibodies in high-risk primary membranous nephropathy (pMN) patients treated with obinutuzumab (OBI), and to evaluate immunological and clinical remission, adverse events, and quality of life. Design: Open-label, single-center, prospective pilot intervention study conducted at Radboud University Medical Center. Population: 20 adult patients with high-risk PMN, defined by proteinuria ≥3.5 g/24h despite 6 months of supportive treatment with ACE inhibitors or ARBs. Intervention: OBI 1000 mg on days 1 and 15, with two additional infusions after 6 months if anti-PLA2R antibody levels remain positive and proteinuria exceeds 2 g/24h. Follow-up: Patients were monitored at baseline, and at weeks 1, 2, 4, 8, 12, 24, 37, and 52.

Conditions

Membranous Nephropathy - PLA2R Induced

Keywords

PLA2R antibody kinetics; membranous nephropathy; obinutuzumab

Outcome Measures

Primary Outcomes (1)

• Disappearance rate of PLA2R antibodies

  To calculate the disappearance rate (half-life) of anti-PLA2R antibodies. Serum PLA2R antibodies will be measured at baseline, 1, 2, 4, 8, 12, 24 37 and 52 weeks after obinutuzumab infusions.

  From baseline to 52 weeks after the first obinutuzumab infusion.

Secondary Outcomes (4)

• Immunological remission

  From baseline to 52 weeks after the last obinutuzumab infusion.

• Clinical efficacy

  From baseline to 52 weeks after the last obinutuzumab infusion.

• Adverse events

  From baseline to 52 weeks after the last obinutuzumab infusion.

• Quality of life during treatment

  From baseline to 52 weeks after the last obinutuzumab infusion.

Study Arms (1)

Treatment with obinutuzumab.

EXPERIMENTAL

Drug: Obinutuzumab administration

Interventions

Obinutuzumab administration DRUG

All participants will receive obinutuzumab 1000 mg on day 1 and 15, with two additional infusions after 6 months if the anti-PLA2R antibody IFT assay is still positive with proteinuria \> 2 gram/24 hours and stable kidney function.

Treatment with obinutuzumab.

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Diagnosis of PMN, confirmed by:
• Kidney biopsy or
• Positive serum PLA2Rab test either by IFT and/or ELISA)
• Serum PLA2Rab titer \> 80 RU/ml
• Proteinuria ≥ 3.5 g/24h despite supportive treatment for at least 6 months with a maximally tolerated and stable dose of ACE-i or ARB.
• Serum albumin \< 30 g/l measured by BCP assay.
• eGFR ≥ 30 ml/min/1.73m2.
• Treatment with immunosuppression is warranted, as determined by the treating physician.

You may not qualify if:

• Secondary MN (e.g., hepatitis B or C infection, human immunodeficiency virus infection, active infection, systemic lupus erythematosus, sarcoidosis, IgG4-related, drug-induced, malignancy).
• Proteinuria must not have decreased by \> 50% over 6 months whilst taking ACEi/ARB.
• Life-threatening nephrotic syndrome resistant to treatment.
• \> 20% increase in serum creatinine not otherwise explained during antiproteinuric supportive treatment.
• Pregnancy or breastfeeding. Women of childbearing age and male patients with female partners of childbearing potential not willing to use contraception throughout the study and for at least 6 months after the last dose of obinutuzumab.
• Suspected or known hypersensitivity, allergy, and/or immunogenic reaction history to monoclonal antibodies, corticosteroid, cyclophosphamide, any of their ingredients, and any other drugs from these same pharmacotherapeutic groups.
• Known active infection of any kind or recent major episode of infection.
• Any disorder or condition which might pose an unacceptable risk to patient's safety and well-being that might interfere with completion of the study.
• Inability to understand or comply with the requirements of the study.
• Incapable of recognizing the nature, significance, and scope of the clinical trial or giving consent even with a legal representative.
• Use of an investigational agent.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Department of Nephrology, Radboud University Medical Center

Nijmegen, Netherlands

RECRUITING

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Anne-Els Van de Logt, M.D., PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruben Visch, M.D.

CONTACT

+31 (0)24 3092575; ruben.visch@radboudumc.nl

Anne-Els van de logt, M.D., PhD

CONTACT

+31611167560; anne-els.vandelogt@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2025
• First Posted: September 9, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: January 6, 2026

Record last verified: 2025-08

Locations

NL (1)