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

Radboud University Medical Center

Status and phase: Unknown; Phase 3

Conditions: Minimal Change Disease; Idiopathic Nephrotic Syndrome; Focal Segmental Glomerulosclerosis

Treatments: Drug: Rituximab; Drug: Prednisone

Study type: Interventional

Funder types: Other

Identifiers

NCT03298698

RSRNS17

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Rituximab

Experimental group

Description:

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).

Treatment:

Drug: Rituximab

Prednisone

Active Comparator group

Description:

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

Treatment:

Drug: Prednisone