Research into the effect of Obinutuzumab on the level of PLA2R antibodies in patients with membranous nephropathy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Radboud universitair medisch centrum Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-07-31

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

F. Hoffmann-La Roche Ltd. will support the study medication (obinutuzumab).

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Therapy

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.

Secondary objectives 4

1. Immunological remission, defined as negative according to the anti-PLA2R antibody immunofluorescence test (IFT).
2. To assess the efficacy of obinutuzumab on disease activity, defined as either complete (CR) or partial (PR) remission at 12 months.
3. To assess adverse events of treatment with obinutuzumab, categorized as SAE or NSAESI, up to 12 months.
4. To determine quality of life (using the 'Kidney Disease Quality of Life-36' questionnaire) during obinutuzumab treatment, average of scores observed at baseline and in week 12, 24, 37 and 52 or up to study exit.

Conditions and MedDRA coding

Primary membranous nephropathy

Regulatory references

Plan to share IPD

Yes

IPD plan description

The individual-level data collected during the trial, including but not limited to demographic information, clinical outcomes, laboratory results, and adverse event data, will be made available for sharing. Because personal data is collected, there are privacy issues. Most data will be published without restrictions, only after an embargo period of 12 months to enable publication of new results based on the data. The pseudonimized data will be accessible under restricted access. Requests for acces will be checked by the PI.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years.
2. Diagnosis of primary membranous nephropathy, confirmed by: a) kidney biopsy or b) positive serum anti-PLA2R antibody test (either by IFT and/or ELISA).
3. Serum anti-PLA2R antibody titer > 80 RU/ml.
4. Proteinuria ≥ 3.5 g/24h despite supportive treatment for at least 6 months with maximally tolerated and stable dose of ACE-inhibitor or ARB.
5. Serum albumin < 30 g/l measured by Bromocresol Purple (BCP) assay.
6. eGFR ≥ 30 ml/min/1.73m2.
7. Treatment with immunosuppression is warranted, as determined by the treating physician.

Exclusion criteria 15

1. Secondary membranous nephropathy (e.g., hepatitis B or C infection, human immunodeficiency virus infection, active infection, systemic lupus erythematosus, sarcoidosis, IgG4-related, drug-induced, malignancy).
2. Rituximab within 12 months prior to inclusion.
3. Calcineurin inhibitor within 2 months prior to inclusion.
4. Treatment with other immunosuppressive drugs within 6 months prior to inclusion.
5. Proteinuria must not have decreased by > 50% over 6 months whilst taking ACE-inhibitor/ARB.
6. Life-threatening nephrotic syndrome resistant to treatment.
7. > 20% increase in serum creatinine not otherwise explained.
8. Pregnancy or breastfeeding.
9. 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.
10. 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.
11. Inability to understand or comply with the requirements of the study.
12. Known active infection or recent major episode of infection.
13. 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.
14. Incapable of recognizing the nature, significance, and scope of the clinical trial or giving consent even with a legal representative.
15. Use of an investigational agent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disappearance rate (half-life) of anti-PLA2R antibodies.

Secondary endpoints 4

1. Immunological remission defined as IFT negative.
2. Efficacy on clinical disease activity, defined as either CR or PR at 12 months.
3. Adverse events.
4. Quality of life during obinutuzumab treatment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Radboud universitair medisch centrum Stichting

Sponsor organisation

Radboud universitair medisch centrum Stichting

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Ruben Visch

Public contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Ruben Visch

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications