Efficacy of Anti-CD20 Ab Associated With Anti-CD38 in the Childhood Multidrug Dependent and Resistant Nephrotic Syndrome

• Status: Not yet recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Nephrotic syndrome is considered a disease caused by an interplay of immunological stimuli with adaptive immunity(CD80/CD40) as trigger and Treg in the mid between co-stimulatory molecules and effectors. The positive effect of drugs blocking CD20 maturation in SDNS suggests a main role of these cells in regulating the system. Multidrug dependent, multidrug resistant nephrotic syndrome as well as post transplant FSGS recurrence patients can be considered difficult to treat patients and the association of two drugs, one targeting CD20 and a targeting plasmacells can be use in order to block the stimulatory cascade at more sites.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Istituto Giannina Gaslini
• Treatments: Daratumumab; Rituximab

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any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject any time without prejudice to his or her future medical care.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