Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome

NCT02438982 | Completed Phase 3 DMC

• 2 other identifiers: pednephro RCT/PM/NRSMCH-54CTRI/2014/01/004355
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Nephrotic syndrome in children is primarily caused by minimal change disease. Majority of these patients respond well to corticosteroids. However, as many as 70% of children with nephrotic syndrome experience at least one relapse, and 30% develop a more complicated course with frequent relapses (FRNS)(≥2 relapses/ 6 months) with or without steroid dependency (SDNS)(relapse during tapering or within 2 weeks after discontinuation of corticosteroids). Repeated and prolonged courses of steroids in these children often result in long-term complications. The goal of the treatment is to reduce the rate of relapses, the cumulative dose of corticosteroids, and the incidence of serious complications. In order to minimize the side effects of steroid therapy, different steroid sparing agents such as cyclophosphamide, calcineurin inhibitors(CNI), levamisole, and mycophenolate mofetil (MMF) have been used in SDNS. Whereas CNI are usually considered the steroid sparing drug class of first choice, rituximab is increasingly used as alternative to minimize CNI toxicity. Various prospective studies suggest that Rituximab, a B cell depleting monoclonal antibody, could be a safe and effective alternative to steroid or immunosuppressants to achieve and maintain remission in this population.Single rituximab course have been shown to be efficacious for 6 to 12 months and the side effect profile observed to date is very benign. Studies comparing the usefulness of these agents are lacking. In our proposed randomized controlled trial, the investigators want to compare the efficacy and safety of CNI to that of Rituximab in treating children with SDNS.

Conditions

Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

• 12-month relapse-free survival

  12-month

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

Oral Tacrolimus (Tablet form) 0.2mg/kg/day starting dose. Targeting trough level of Tacrolimus (T0) 5-7 ng/ml.

Drug: Tacrolimus

Rituximab

EXPERIMENTAL

Two rituximab infusions will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2). Circulating B cells will be measured 24 hours after rituximab administration. If \>5 B cells per mm3 , it will be measured again after 1 week. If count is still \>5 B cells per mm3, third \& fourth doses of rituximab will be given.

Drug: Rituximab

Interventions

Tacrolimus DRUG

Oral Tacrolimus (Tablet form) 0.2mg/kg/day starting dose. Targeting trough level of Tacrolimus (T0) 5-7 ng/ml.

Also known as: Calcineurin inhibitor

Tacrolimus

Rituximab DRUG

Two rituximab infusions will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2). Circulating B cells will be measured 24 hours after rituximab administration. If \>5 B cells per mm3, it will be measured again after 1 week. If count is still \>5 B cells per mm3, third \& fourth doses of rituximab will be given.

Also known as: anti CD20 monoclonal antibody

Rituximab

Eligibility Criteria

• Age: 3 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children between 3 and 16 years with SDNS
• Minimal Change disease/FSGS/MesPGN/ as per Kidney Biopsy report.
• Estimated glomerular filtration rate (eGFR) \>80 ml/min per 1.73 m2 at study entry.
• Remission at study entry (trace or nil proteinuria, as determined by the dipstick test or \<100 mg/dl for at least 3 days).
• Not received any steroid sparing agent previously.
• Parents willing to give informed written consent.
• Ability to swallow tablet

You may not qualify if:

• Known etiology (e.g., lupus erythematosus, IgA nephropathy, amyloidosis, malignancy, other secondary forms of NS)
• Patients with severe leucopenia (leucocytes \<3.0× 1000 cells/mm3), severe anemia (haemoglobin \<8.9 g/dl), thrombocytopenia (platelet \<100.0 × 1000 cells/mm3) or deranged liver function tests (AST or ALT to \>50 IU/L ) at enrolment.
• Known active chronic infection (tuberculosis, HIV, hepatitis B or C) Live vaccination within 1 mo

Sponsors & Collaborators

• Nilratan Sircar Medical College: lead

Study Sites (1)

NRS Medical College & Hospital

Kolkata, West Bengal, 700014, India

Location

Related Publications (2)

• Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.

  PMID: 39513526 DERIVED

• Basu B, Sander A, Roy B, Preussler S, Barua S, Mahapatra TKS, Schaefer F. Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial. JAMA Pediatr. 2018 Aug 1;172(8):757-764. doi: 10.1001/jamapediatrics.2018.1323.

  PMID: 29913001 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Tacrolimus; Calcineurin Inhibitors; Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Biswanath Basu

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor & In charge, Division of Pediatric Nephrology

Study Record Dates

• First Submitted: May 6, 2015
• First Posted: May 8, 2015
• Study Start: May 8, 2015
• Primary Completion: August 1, 2016
• Study Completion: September 1, 2016
• Last Updated: August 1, 2017

Record last verified: 2017-07

Locations

IN (1)