Combining two monoclonal antibodies to treat difficult nephrotic syndrome in children

Efficacy of Chimeric Monoclonal Anti-CD20 Antibodies (Rituximab Biosimilar) Associated With Monoclonal Anti-CD38 (Daratumumab) in the Treatment of Childhood Multidrug Dependent and Resistant (MDNS, MRNS) Nephrotic Syndrome

This study is testing if combining two specific antibodies can help children aged 3 to 24 with tough-to-treat nephrotic syndrome feel better when other medicines haven't worked.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 3 Years to 24 Years
• Sex: All
• Sponsor: Istituto Giannina Gaslini (Academic / other)
• Drugs / interventions: Rituximab, cyclophosphamide, prednisone, obinutuzumab, daratumumab
• Locations: 1 site (Genova)
• Trial ID: NCT05704400 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of combining two monoclonal antibodies, Rituximab Biosimilar ABP 798 and Daratumumab, to treat childhood nephrotic syndrome that is resistant to multiple drugs. The study focuses on patients aged 3 to 24 years who have been dependent on or resistant to standard treatments for at least six months. By targeting CD20 and plasmacells, the trial aims to block the immunological pathways contributing to the disease. The approach is based on previous positive outcomes from similar treatments in a small cohort of patients.

Who should consider this trial

Good fit: Ideal candidates are children aged 3 to 24 years with a history of multidrug dependent or resistant nephrotic syndrome.

Not a fit: Patients who do not have nephrotic syndrome or those who are not resistant to standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for children suffering from multidrug dependent and resistant nephrotic syndrome.

How similar studies have performed: Previous studies have shown positive outcomes with similar combinations of monoclonal antibodies, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Age between 3 and 24 years
* Multidrug dependent or resistant nephrotic syndrome for at least six months before enrolment. The need of at least 2 of the oral drugs listed below defines multidrug-dependence: prednisone at any doses, MMF 1200 mg m2 and CNI 0.1 mg day given in two doses. Dependence is defined by two consecutive relapses during double therapies or within 14 days of ceasing one of the three components of the therapeutic approach. Resistance is defined as lack of antiproteinuric effect of a double therapy based on steroid plusCNI or mofetilmycophenolate (MMF).Steroid resistance is defined by failure to achieve complete remission after 6 weeks with prednisone60 mg/m2.
* Post transplant recurrence of FSGS.
* Ability to provide consent and assent: parents'/guardian's written informed consent, and child's assent given before any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject any time without prejudice to his or her future medical care.

Exclusion Criteria:

* Positivity to autoimmunity tests (ANA, nDNA, ANCA)
* Reduction of C3 levels.
* eGFR\<60/ml/min/1,73 m2 valuated according to revised Bedside Schwartz Formula for patients between 2 and 17 years and with CKD-EPI Creatinine 2009 Equation for 18 years old patients.
* Pregnancy
* Neoplasm
* Infections: previous or actual HBV (with HBeAb positivity) or HCV infection
* CD20 B lymphocytes count \<2,5%
* Treatment with Rituximab or cyclophosphamide in the last 6 months

Where this trial is running

Genova

• IRCCS G. Gaslini — Genova, Italy (Recruiting)

Study contacts

• Principal investigator: Gianmarco Ghiggeri, MD — IRCCS G. Gaslini
• Study coordinator: Gianmarco Ghiggeri, MD

Conditions Nephrotic Syndrome