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

NCT ID: NCT03298698

Last Updated: 2018-08-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-22
• Study Completion Date: 2022-01-22

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.

Detailed Description

Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are important causes of idiopathic nephrotic syndrome. First-line treatment with high dose prednisone up to 16 weeks is associated with serious side effects. Especially if treatment continues for more than 8 weeks.

Retrospective studies suggested that Rituximab may be more effective in patients unresponsive to 8 weeks of high dose prednisone. Treatment with rituximab was associated with a higher proportion of patients attaining remission of proteinuria and with fewer side effects.

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 an idiopathic nephrotic syndrome due to biopsy proven MCD or FSGS age 18 years or older.

All patients will be treated with high dose prednisone (1 mg/kg/day) for 8 weeks.

Patients can be included in the trial in case of persistent 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

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. In the Rituximab group, 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 (maximum of 2 additional doses) until complete B cell depletion.

Expected duration of the follow-up is 12 months, consisting of 9 visits.

Conditions

Idiopathic Nephrotic Syndrome; Minimal Change Disease; Focal Segmental Glomerulosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

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).

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: 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).

Prednisone

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

Group Type: ACTIVE_COMPARATOR

Prednisone

Intervention Type: DRUG

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

Interventions

Rituximab

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).

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Other Intervention Names

Mabthera; Prednisolone

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Patients inoculated with a vaccine within 4 weeks prior to inclusion
• Pregnancy, breast feeding, women with inadequate contraception
• Malignancy
• Kidney transplantation
• Previous treatment with monoclonal antibodies within 2 years prior to inclusion
• 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
• Severe osteoporosis with vertebral fracture

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeroen K Deegens, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Nijmegen Medical center

Jack F Wetzels, MD, PhD

Role: STUDY_CHAIR

Radboud University Nijmegen Medical Center

Locations

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Jeroen Deegens, MD,PhD

Role: CONTACT

Jeroen.Deegens@radboudumc.nl

+31243614761

Facility Contacts

Jeroen K Deegens, MD, PhD

Role: primary

Jeroen.Deegens@radboudumc.nl

+31243614761

Jack F Wetzels, MD, PhD

Role: backup

Jack.Wetzels@radboudumc.nl

+31243614761

References

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.

Reference Type: DERIVED

PMID: 35230699 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35224732 (View on PubMed)

Other Identifiers

RSRNS17

Identifier Type: -

Identifier Source: org_study_id