Clinical Trial Results:
Randomised Trial of Anti-CD20 in C4d+ Chronic Allograft Nephropathy
Summary
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EudraCT number |
2006-002330-38 |
Trial protocol |
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Global end of trial date |
09 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Jun 2019
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First version publication date |
23 Jun 2019
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Other versions |
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Summary report(s) |
FINAL STUDY REPORT |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RituxiCAN-C4
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00476164 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
King's College London
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Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
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Public contact |
Professor Anthony Dorling, Kings College London, 44 020 7188 8711, anthony.dorling@kcl.ac.uk
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Scientific contact |
Professor Anthony Dorling, Kings College London, 44 020 7188 8711, anthony.dorling@kcl.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Mar 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Mar 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Mar 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
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.
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Protection of trial subjects |
During the initial phase of the run-in period, the following standard clinical therapies will be introduced and/or optimised according to the following guidelines;
• Mycophenolate mofetil bd, or enteric coated mycophenolic acid bd, with dose determined according to local unit guidelines. In those centres monitoring MPA levels, dose will be titrated to achieve plasma 12-hour post-dose levels of 1.6-2.75. In these centres, the starting dose will be 500mg bd in patients not already on MMF
• Tacrolimus bd titrated to achieve 12-hour post-dose levels of 4-8. Starting dose 0.05mg/kg bd in patients not already on Tacrolimus
• Statin therapy to achieve total non-fasting cholesterol to ≤ 4.5
• ACE-I and ARB combination therapy to achieve a target bp of ≤140/≤80
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Background therapy |
Optimised Tacrolimus, MMF, ACE-I/ARB, statins | ||
Evidence for comparator |
n/a | ||
Actual start date of recruitment |
12 Apr 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 23
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Worldwide total number of subjects |
23
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EEA total number of subjects |
23
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
22
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited from 16 sites across the UK | |||||||||||||||
Pre-assignment
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Screening details |
All eligible patients will be undergo a run-in period during which time standard therapy will be optimised (0-2 months) followed by 3 months on fully optimised therapy. At the end of the run-in, graft function and degree of proteinuria will be re-assessed and patients who still meet the criteria for entrance into the study. | |||||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
Not applicable
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Control Arm | |||||||||||||||
Arm description |
Control group were randomised to stay on standard therapy with the formal 3-month analysis period will begin on the day of randomisation. | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Rituximab Arm | |||||||||||||||
Arm description |
Participants in the Rituximab arm received two 1g infusions 14 days apart, administered with paracetamol and chlorphenamine +/- hydrocortisone followed by co-trimoxazole (or alternative) for 6 months. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Rituximab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received Rituximab 1g infusions on two occaisions 14 days apart.
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Baseline characteristics reporting groups
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Reporting group title |
Control Arm
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Reporting group description |
Control group were randomised to stay on standard therapy with the formal 3-month analysis period will begin on the day of randomisation. | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rituximab Arm
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Reporting group description |
Participants in the Rituximab arm received two 1g infusions 14 days apart, administered with paracetamol and chlorphenamine +/- hydrocortisone followed by co-trimoxazole (or alternative) for 6 months. | ||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Control Arm
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Reporting group description |
Control group were randomised to stay on standard therapy with the formal 3-month analysis period will begin on the day of randomisation. | ||
Reporting group title |
Rituximab Arm
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Reporting group description |
Participants in the Rituximab arm received two 1g infusions 14 days apart, administered with paracetamol and chlorphenamine +/- hydrocortisone followed by co-trimoxazole (or alternative) for 6 months. |
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End point title |
Rate of deterioration of renal function [1] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At least 6 data points over three months
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see final study report for details of analysis. |
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Attachments |
FINAL STUDY REPORT |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
AEs will be recorded from consent up to the primary end-point.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Control Arm
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Reporting group description |
Control group were randomised to stay on standard therapy with the formal 3-month analysis period will begin on the day of randomisation. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rituximab Arm
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Reporting group description |
Participants in the Rituximab arm received two 1g infusions 14 days apart, administered with paracetamol and chlorphenamine +/- hydrocortisone followed by co-trimoxazole (or alternative) for 6 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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19 Oct 2009 |
Change of Sponsor from Imperial College London to King's College London |
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14 Feb 2010 |
a) Addition of “administration of lymphocyte depleting antibody within 3 months of enrolment” to the exclusion criteria.
b) Requirement for units to give 6 months of prophylactic co-trimoxazole to all patients receiving rituximab. The dose will be that used by each unit for prophtlaxis. |
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20 Dec 2010 |
Allow use enteric coated mycophenolic acid instead of MMF.
Allow use imaging techniques other than MRA.
Amended IMP labels |
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07 Feb 2012 |
Two changes have been made to the exclusion criteria, the first to reflect a difficulty the trial team have had in obtaining timely imaging to exclude renal artery stenosis (which after 40 recruits has not excluded anybody), and the second to reflect a minor change in the SmPC for rituximab. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |