The Use of Rituximab IN treatment of immune-mediated Glomerulonephritis (TURING)

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2018-004611-50-GB
• Date of registration: 11/04/2019
• Prospective Registration: Yes
• Primary sponsor: Cambridge University Hospitals NHS Foundation Trust
• Public title: The Use of Rituximab IN treatment of immune-mediated Glomerulonephritis (TURING)
• Scientific title: A randomised, two-arm (1:1 ratio), double blind, placebo controlled phase III trial to assess the efficacy, safety, cost and cost-effectiveness of rituximab in treating de novo or relapsing NS in patients with MCD/FSGS (TURING) - TURING
• Date of first enrolment: 14/06/2019
• Target sample size: 112
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004611-50
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Mrs Carrie Bayliss
• Affiliation: Cambridge University Hospitals NHS Foundation Trust - Cambridge Clinical Trials Unit

• Name: Mrs Carrie Bayliss
• Affiliation: Cambridge University Hospitals NHS Foundation Trust - Cambridge Clinical Trials Unit

Key inclusion & exclusion criteria

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).




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:
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







Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Minimal Change Disease (MCD) and Focal segmental glomerulosclerosis (FSGS)

Intervention(s)

Product Name: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
CAS Number: 0174722-31-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To assess the efficacy of rituximab on the time to relapse of NS from partial/complete remission

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 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

Secondary Outcome(s)

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

Secondary ID(s)

CCTU0228

Source(s) of Monetary Support

NIHR HTA

Ethics review

Status: Approved
Approval date:
Contact: