|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Minimal Change Disease (MCD) and Focal segmental glomerulosclerosis (FSGS)
|Medical condition in easily understood language
|These are auto-immune renal diseases that present with a common clinical phenotype, the nephrotic syndrome (NS).
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To assess the efficacy of rituximab on the time to relapse of NS from partial/complete remission
|Secondary objectives of the trial
|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
|Trial contains a sub-study
|Principal inclusion criteria
|To be included in the trial the participant must:
• Age 16 years or older.
• NS at trial entry (serum albumin < 35g/l and protein creatinine ratio (PCR) >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).
|Principal 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
|E.5 End points
|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): PCR<50mg/mmol (only one result required).
PARTIAL REMISSION (PR): Reduction in Urinary PCR≥ 50% from Day 0 - Start of Protocolised Prednisolone Regimen (SPPR) AND PCR ≥50mg/mmol and ≤300mg/mmol on two consecutive results. The date of first assessment is the date of partial remission.
RELAPSE: recurrent NS as defined by albumin < 35 g/l, PCR >300mg/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 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)
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
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The end of trial will be 30 months after the last patient has been recruited or a minimum of 76 primary outcome events have been observed, whichever occurs later.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days