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

NCT05704400 | Unknown Phase 2 DMC

• 1 other identifier: DUAL1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nephrotic Syndrome

Outcome Measures

Primary Outcomes (2)

• Safety- number of treatment-related adverse events

  Primary: to test whether the combination of rituximab and daratumumab is safe and can achieve and maintain drug-free disease remission in patients with multi drug-dependent nephrotic syndrome within 12 months. The investigators will consider the number of participants with treatment-related adverse events as assessed by CTCAE v4.0 This outcome will not be compared but only studied following the intervention.

  12 months

• Efficacy- number of months in remission

  To test whether the combination of rituximab and daratumumab can achieve and maintain drug-free disease remission in patients with multi drug-dependent nephrotic syndrome within 12 months The investigators will compare the outcome of log-albuminuria following the infusion of the two drugs to the log-albuminuria before the infusion, when patients were maintained by the association of MMF and CNI (i.e. the drug recommended by Clinical Practice Guidelines-KDIGO as benchmark of the treatment).

  12 months

Secondary Outcomes (1)

• Prediction

  12 months

Study Arms (1)

single arm

EXPERIMENTAL

Drug: Rituximab Biosimilar ABP 798; Drug: Daratumumab

Interventions

Rituximab Biosimilar ABP 798 DRUG

Rituximab IV: the dose is standard for pediatric nephrotic syndrome; for dosage between 100 and 250 mg rituximab will be diluted in 100 ml of normal saline and administered at 2 ml/h for the first 30'; 3 ml/h for the second 30'; 6 ml/h for the third 30'; 15 ml/h until the end. For dosage between 260 and 500 mg rituximab will be diluted in 250 ml of normal saline and administered at 6 ml/h for the first 30'; 9 ml/h for the second 30'; 18 ml/h for the third 30'; 36 ml/h until the end. For dosage between 510 and 1000 mg rituximab will be diluted in 500 ml of normal saline and administered at 9 ml/h for the first 30'; thereafter, the infusion rate can be doubled every 30 minutes up to a maximum of 72 ml/h.

single arm

Daratumumab DRUG

Daratumumab vials 20 mg 1 ml will be collected to reach the desired dose of 16 mg /Kg, the dose is standard recommend to treat myeloma; diluted in 1000 ml of normal saline and infused at the constant speed of 50 ml/h. This will be reduced in case of cutaneous allergic reactions

single arm

Eligibility Criteria

• Age: 3 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituto Giannina Gaslini: lead

Study Sites (1)

IRCCS G. Gaslini

Genova, 16148, Italy

RECRUITING

Related Publications (1)

• Angeletti A, Bruschi M, Kajana X, La Porta E, Spinelli S, Caridi G, Lugani F, Verrina EE, Ghiggeri GM. Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment. Front Immunol. 2023 Aug 29;14:1213203. doi: 10.3389/fimmu.2023.1213203. eCollection 2023.

  PMID: 37705972 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Gianmarco Ghiggeri, MD

  IRCCS G. Gaslini

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gianmarco Ghiggeri, MD

CONTACT

+39010-56363523; gmarcoghiggeri@gaslini.org

Andrea Angeletti, MD, PhD

CONTACT

+39010-56363523; andreaangeletti@gaslini.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Phase II Proof of concept, the Dual 1 is a before-after clinical trial testing the superiority of rituximab plus daratumumab in maintaining drug free disease remission in patients with multi-drug dependent nephrotic syndrome

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: January 30, 2023
• Study Start: March 1, 2023
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2025
• Last Updated: October 31, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

IT (1)