Randomised Trial of Rituximab in C4d+ Chronic Renal Transplant Rejection

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2006-002330-38-GB
• Date of registration: 16/10/2006
• Prospective Registration: Yes
• Primary sponsor: King's College London
• Public title: Randomised Trial of Rituximab in C4d+ Chronic Renal Transplant Rejection
• Scientific title: Randomised Trial of Anti-CD20 in C4d+ Chronic Allograft Nephropathy - RituxiCAN-C4
• Date of first enrolment: 22/11/2006
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002330-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: Standard optimal clinical care according to our unit protocol; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Contacts

• Name: Joint Clinical Trials Office
• Affiliation: Kings College London

• Name: Joint Clinical Trials Office
• Affiliation: Kings College London

Key inclusion & exclusion criteria

Inclusion criteria:
To be included in the study the patient must have:
•A functioning kidney allograft (with estimated GFR by MDRD >20) and be >6/12 post-transplantation
•Either deteriorating allograft function as defined by linear regression of reciprocal creatinine plot. Deterioration will be defined as a negative slope over at least the preceding 3 months (with at least 6 creatinines included) with an adjusted r2 >0.35 and a p value of =0.05 compared to horizontal baseline. Deterioration will be confirmed by Cockcroft Gault eGFR somparisons over same period to rule out body mass as a cause of change in creatinines
OR Significant proteinuria defined as a urine protein : creatinine ratio =50
OR Both deteriorating function and proteinuria
•CAN, by Banff ’97 criteria, or transplant glomerulopathy on renal allograft biopsy performed within 3/12 of enrolment
•Diffuse, linear C4d deposition on at least 25% of peritubular capillary (PTC) and/or glomerular EC of renal transplant biopsy when assessed by immunoperoxidase OR >50% of PTC (alone) when assessed by immunofluorescence.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
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 patient inclusion

•<18 years of age
•suspicion of pregnancy confirmed by positive HCG pregnancy test
•untreated ureteric obstruction on ultrasound of allograft
•history of acute allograft rejection in preceding 3/12
•history of MI in preceding 3/12
•history of malignancy in previous 5 years (excluding tumours limited to skin)
•symptomatic IHD
•recipient of simultaneous pancreas/kidney transplant
•recipient of ABO-incompatible kidney
•recipient who underwent an HLA desensitisation procedure prior to transplantation
•evidence, on examination of renal allograft biopsy specimen, of recurrent or de-novo disease (except IgA deposition in absence of mesangial proliferation)
• evidence, on examination of renal allograft biopsy specimen, of CNI toxicity IF ACCOMPANIED by mostly supra-therapeutic CNI trough levels in the 6 month period preceding biopsy.
• doumented allergy to mouse or chimeric human/mouse proteins
• HepBsAg+, HCV Ab+ or HIV+ or HepBcAb+
• administration of lymphocyte depleting antibody within 3 months of enrolment


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

Health Condition(s) or Problem(s) studied

Renal Transplant Rejection - chronic
MedDRA version: 14.1 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Trade Name: MabThera
Product Name: N/A
Product Code: N/A
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
Other descriptive name: Anti-CD20 monoclonal Ab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-50

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Determined 3-5 months post-randomisation

Primary end point(s): •Rate of deterioration in renal function, defined by slope of reciprocal creatinine plot, on samples taken in the preceding 3 months.
•Change in degree of proteinuria, where present

Main Objective: To determine whether anti-CD20 therapy can stabilise or improve renal function and/or proteinuria in patients with C4d+, chronic (humoral) rejection in whom standard therapeutic approaches have failed.

Secondary Objective: To compare patient and graft survival between control and rituximab-treated groups
To evaluate the adverse effect profile of rituximab in this group
To correlate changes in circulating B cell numbers, anti-HLA and non-HLA Ab profiles and titre with responses to standard therapy and / or rituximab
To correlate changes in T cell responsiveness to alloantigens with responses to standard therapy and / or rituximab

Secondary Outcome(s)

Secondary end point(s): To compare patient and graft survival between control and rituximab-treated groups
To evaluate the adverse effect profile of rituximab in this group
To correlate changes in circulating B cell numbers, anti-HLA and non-HLA Ab profiles and titre with responses to standard therapy and / or rituximab
To correlate changes in T cell responsiveness to alloantigens with responses to standard therapy and / or rituximab

Timepoint(s) of evaluation of this end point: Secondary endpoints will be determined at 3-5 months post-randomisation and at 1, 2 and 3 years post-recruitment

Secondary ID(s)

RituxiCAN-C4

Source(s) of Monetary Support

Roche

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 23/06/2019
• Date Completed: 09/03/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-002330-38/results