Obinutuzumab Induced Decreases of PLA2R Antibodies in Membranous Nephropathy: a Pilot Study
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorRadboud University Medical Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years.
Kidney biopsy or
Positive serum PLA2Rab test either by IFT and/or ELISA)
Serum PLA2Rab titer > 80 RU/ml
Disqualifiers
Secondary MN (e.g., hepatitis B or C infection, human immunodeficiency virus infection, active infection, systemic lupus erythematosus, sarcoidosis, IgG4-related, drug-induced, malignancy).
RTX within 12 months prior to inclusion.
CNI within 2 months prior to inclusion.
Treatment with other immunosuppressive drugs within 6 months prior to inclusion.
Trial design
Design model
Single group
Treatments tested in this trial
Obinutuzumab administration
DrugAll 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 groups
20 Participants
are divided into 1 treatment groupGroup A: Treatment with obinutuzumab.Experimental treatment 1 intervention
Trial outcomes
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.
Time frame
From baseline to 52 weeks after the first obinutuzumab infusion.Secondary outcomes
1
Immunological remission
Immunological remission, defined as negative accorording to the anti-PLA2R antibody immunofluorescence test (IFT).
Time frame
From baseline to 52 weeks after the last obinutuzumab infusion.2
Clinical efficacy
To assess efficacy of obinutuzumab on disease activity, defined as either complete remission (CR) or partial remission (PR).
Time frame
From baseline to 52 weeks after the last obinutuzumab infusion.3
Adverse events
To assess adverse events of treatment with obinutuzumab, categorized as SAE or NSAESI.
Time frame
From baseline to 52 weeks after the last obinutuzumab infusion.4
Quality of life during treatment
To determine quality of life (Kidney Disease Quality of Life-36) during obinutuzumab treatment.
Time frame
From baseline to 52 weeks after the last obinutuzumab infusion.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Radboud University Medical Center
Lead sponsor
Hoffmann-La Roche
Collaborator
Source ClinicalTrials.gov