Minimal Change Disease (MCD) and Focal segmental glomerulosclerosis (FSGS)
Conditions
Interventions
Product Name: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
CAS Number: 0174722-31-7
Sponsors
Cambridge University Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be included in the trial the participant must: • Age 16 years or older. • NS at trial entry (serum albumin 300mg/mmol) secondary to MCD/FSGS with, • De novo disease or relapsing disease in a patient previously steroid or calcineurin inhibitor (CNI) responsive. • Latest biopsy (at any time) proven MCD/FSGS. • Ability to provide written informed consent. • Agreed to be enrolled in the National Registry of Rare Kidney Disease (RaDaR). Are the trial subjects under 18? yes Number of subjects for this age range: 5 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: The presence of any of the following will preclude participant inclusion: • MCD or FSGS due to secondary causes, including obesity-driven hyperfiltration, remnant kidneys, malignancy of a type likely to be associated with MCD /FSGS and genetic polymorphisms known to be associated with nephrosis • MCD/FSGS secondary to malignancy, including lymphoproliferative disorders • Family history of MCD or FSGS in a first degree relative • Previous rituximab within 18 months preceding Day 0 (SPPR), or 12 months if there is evidence of B cell return in peripheral lymphocyte subsets • Previous cyclophosphamide within 6 months preceding Day 0 (SPPR) • Prednisolone daily dose equal to or greater than 60mg, with a course length of greater than4 weeks, immediately prior to randomisation • Evidence of current or past infection with Hepatitis B, C or HIV (unless appropriate prophylaxis is given and no replicating virus is detected). • Positive serum pregnancy test (within 14 days prior to treatment with IMP in main trial and rituximab in OLP) • Evidence of active severe infection • Severe heart failure or severe, uncontrolled cardiac disease • Pregnant or breast-feeding women • Live vaccine administration in the four weeks prior to enrolment and while remaining on IMP treatment • Previous/known hypersensitivity to prednisolone or IMP or to murine proteins (and any excipients as described in section 6.1 of the SmPC). • Co-enrolment in another clinical trial of an investigational medicinal product • Any other reason which, in the opinion of the Principal Investigator (PI), renders the patient unsuitable for the trial. • An increase in CNI dose in the four weeks preceding randomisation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of rituximab on the time to relapse of NS from partial/complete remission ; Secondary Objective: To assess the effect of rituximab on NHS and societal resource use and hence cost. To assess the effect of rituximab on safety and on secondary measures of efficacy, such as achievement of remission of NS and the preservation of renal function To assess the effect of rituximab on patient reported health status ; Primary end point(s): Primary outcome measure: Time from partial or complete remission (whichever documented first) to relapse of NS as defined below: COMPLETE REMISSION (CR): PCR300mg/mmol and an increase in 50% over the nadir value during remission on two consecutive results. The date of first assessment is the date of relapse. For patients with an albumin >35g/l prior to relapse, only one PCR result is required (ie PCR > 300mg/mmol that has risen by 50% over the nadir value and an albumin < 35g/L). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary assessments will include an evaluation of the effect of rituximab on: ? Proportion of patients achieving partial or complete remission ? Time to partial or complete remission from Day 0 (SPPR) ? Serious AEs ? AE of Special Interest, including infection and steroid-associated side effects ? Change in urinary PCR/24 hour proteinuria ? Change in serum albumin ? Kidney function as assessed by the change in Glomerular filtration rate (GFR) from Day 0 - Start of Protocolised Prednisolone Regimen (SPPR) to 24 months and to trial end ? Health Status (EQ5D5L) ? Resource use, cost and cost-effectiveness | — |
Countries
United Kingdom
Contacts
Public ContactMrs Carrie Bayliss
Cambridge University Hospitals NHS Foundation Trust - Cambridge Clinical Trials Unit
Outcome results
None listed