Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome

NCT03298698 | Unknown Phase 3

• 1 other identifier: RSRNS17
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This will be an open-label, randomized controlled trial which compares continued treatment with high dose prednisone (standard therapy) to treatment with rituximab in patients with minimal change disease or focal segmental glomerulosclerosis unresponsive to 8 weeks of high dose prednisone . patients either receive 2 doses of Rituximab 375 mg/m2 iv at time 0 and 14 days with termination of prednisone or standard therapy which consist of 8 additional weeks of high dose prednisone treatment.

Conditions

Idiopathic Nephrotic Syndrome; Minimal Change Disease; Focal Segmental Glomerulosclerosis

Keywords

Idiopathic nephrotic syndrome; Minimal change disease; Focal segmental glomerulosclerosis; Rituximab; Randomized clinical trial

Outcome Measures

Primary Outcomes (1)

• Complete remission

  The proportion of patients reaching complete remission defined as proteinuria \<0.3 g/day or \< 300 mg/g

  8 weeks

Secondary Outcomes (15)

• Partial remission

  8 weeks

• Late complete or partial remission

  2-12 months

• Time to remission

  12 months

• Time to relapse

  12 months

• Proportion of patients with a relapse

  12 months

Study Arms (2)

Rituximab

EXPERIMENTAL

Rituximab: 375 mg/m2 intravenously on day 0 and day 14 B-cells will be monitored weekly, and if no complete depletion is achieved, additional dose(s) of Rituximab will be given at a weekly interval until complete B cell depletion (maximum of 2 additional doses).

Drug: Rituximab

Prednisone

ACTIVE COMPARATOR

Prednisone 1 mg/kg/day (max 80 mg/day) for 8 weeks

Drug: Prednisone

Interventions

Rituximab DRUG

Rituximab: 375 mg/m2 intravenously on day 0 and day 14 B-cells will be monitored weekly, and if no complete depletion is achieved, additional dose(s) of Rituximab will be given at a weekly interval until complete B cell depletion (maximum of 2 additional doses).

Also known as: Mabthera

Rituximab

Prednisone DRUG

Prednisone 1 mg/kg/day (max 80 mg/day) for 8 weeks

Also known as: Prednisolone

Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Persistent proteinuria ≥ 2 g/ 24 hours or a protein-to-creatinine ratio ≥ 2 g/10mmol (2 g/g) after 8 weeks of treatment with high dose prednisone 1 mg/kg/day (max 80 mg/day)
• Idiopathic nephrotic syndrome caused by biopsy proven minimal change disease or focal segmental glomerulosclerosis

You may not qualify if:

• Severe nephrotic syndrome with hypotension
• Previous treatment with immunosuppressive medication other than prednisone
• Treatment with prednisone \> 10 weeks in last six months
• Secondary form of FSGS or minimal change disease
• Patients who test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc).
• Patients infected with HIV or suffering from other active infections
• Pregnancy, breast feeding, women with inadequate contraception
• Malignancy
• Kidney transplantation
• Neutrophils \< 1.5 x 109/L and/or platelet counts \< 75 x 109/L
• Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
• Active peptic ulcer
• Known hypersensitivity to glucocorticoids
• Insulin resistant diabetes mellitus
• Treatment with carbamazepine, phenobarbital, phenytoin en rifampicin

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Medical Center

Nijmegen, 6500HB, Netherlands

RECRUITING

Related Publications (2)

• Azukaitis K, Palmer SC, Strippoli GF, Hodson EM. Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2022 Mar 1;3(3):CD001537. doi: 10.1002/14651858.CD001537.pub5.

  PMID: 35230699 DERIVED

• Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.

  PMID: 35224732 DERIVED

MeSH Terms

Conditions

Nephrosis, Lipoid; Glomerulosclerosis, Focal Segmental

Interventions

Rituximab; Prednisone; Prednisolone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Study Officials

• Jeroen K Deegens, MD,PhD

  Radboud University Nijmegen Medical center

  PRINCIPAL INVESTIGATOR

• Jack F Wetzels, MD, PhD

  Radboud University Nijmegen Medical Center

  STUDY CHAIR

Central Study Contacts

Jeroen Deegens, MD,PhD

CONTACT

+31243614761; Jeroen.Deegens@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: October 2, 2017
• Study Start: August 22, 2018
• Primary Completion: August 22, 2021
• Study Completion: January 22, 2022
• Last Updated: August 27, 2018

Record last verified: 2018-08

Locations

NL (1)