Study Comparing Efficacy and Safety of Mycophenolate Mofetil (Cellcept) With Delayed Introduction of Sirolimus and Discontinuation of Cyclosporine, With Those of Mycophenolate Mofetil and Long Term Continuation of Cyclosporine in Renal Transplant Recipients
Multicentre, Prospective, Randomized, Open-label Study Comparing the Efficacy and Safety of CellCept With Delayed Introduction of Sirolimus and Discontinuation of Cyclosporine, With Those of Standard Immunosuppression Comprising CellCept and Long-term Continuation of Cyclosporine in Renal Transplant Recipients Receiving Induction by Zenapax and Treated With Corticosteroids for 8 Months
1 other identifier
interventional
237
1 country
17
Brief Summary
This multicentre, prospective, randomized, open-label study will compare the safety and efficacy of mycophenolate mofetil with delayed introduction of sirolimus and discontinuation of cyclosporine, with those of mycophenolate mofetil and long term continuation of cyclosporine in renal transplant recipients receiving daclizumab (Zenapax) as induction treatment and followed by 8 month treatment with corticosteroids. The anticipated time on study treatment is 12 months. Participants who will complete the initial 12-month study and who will provide written informed consent will be eligible to participate in a 60-month follow-up phase.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2004
Longer than P75 for phase_3
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2011
CompletedFirst Submitted
Initial submission to the registry
February 16, 2016
CompletedFirst Posted
Study publicly available on registry
February 19, 2016
CompletedFebruary 19, 2016
February 1, 2016
6.2 years
February 16, 2016
February 16, 2016
Conditions
Outcome Measures
Primary Outcomes (7)
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Month 60
60 months
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Up to approximately 12 months
Number of Participants With Serious Adverse Events (SAEs)
From 12 months up to 60 months
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Week 52
52 weeks
Number of Participants With Cancers and Lymphoproliferative Syndromes
Up to approximately 12 months
Number of Participants With Premature Discontinuations due to Adverse Events (AEs)
Up to approximately 12 months
Change From Baseline in 24-Hour Urinary Protein at Week 52
52 weeks
Secondary Outcomes (10)
Mean Inverse Creatinine Concentration
Week 4, 8, 12, 14, 16, 26, 39, and 52
Creatinine Clearance Calculated and Corrected According to Cockcroft-Gault
Week 4, 8, 12, 14, 16, 26, 39, and 52
Glomerular Filtration Rate (GFR) Measured by Iohexol Clearance
Baseline, Week 52
Number of Participants with Response to Treatment, Defined as Creatinine Clearance >/=60 mL/min at Week 52
Week 52
Number of Participants With Treated Rejections
Baseline up to Week 52
- +5 more secondary outcomes
Study Arms (2)
Mycophenolate Mofetil + Cyclosporine
ACTIVE COMPARATORParticipants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months.
Mycophenolate Mofetil + Sirolimus
EXPERIMENTALParticipants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study.
Interventions
Cyclosporine tablets orally once daily at dose level adapted to maintain concentration at 2 hours after administration (C2): 1000-1500 nanogram per milliliter (ng/mL) during Day 0 to Week 4, and 800-1200 ng/mL during Week 4 to Week 52. For Mycophenoate Mofetil + Sirolimus treatment arm, at Week 12, dose of cyclosporine will be reduced by 50% for 3 days, followed by 1/4 of the dose for 3 days, and then cyclosporine will be stopped.
Daclizumab 2 milligram (mg) per kilogram (kg) will be administered as intravenous infusion over 15 minute on Day 0 (during the 24 hours preceding renal transplantation) and at a dose of 1 mg/kg on Day14.
Mycophenoate mofetil 1 gram (g) (2\*500mg tablets or 4\*250mg capsules) will be given twice daily (daily dose of 2 g) orally for 12 months.
Prednisolone 250 mg intravenously on Day 0, followed by 0.5 mg/kg orally daily (maximum 40 mg daily) from Day 1 to Day 7, then 0.25 mg/kg orally daily (maximum 20 mg daily), then dose will be stepwise reduced by 2.5 mg per week to reach to a dose level of 10 mg daily and continued up to 6 months and finally drug will be discontinued after 8 months.
Sirolimus tablets will be given orally from week 12 to week 52, starting with loading dose of 10 mg daily for 2 days followed by 6 mg daily to adapt to trough concentrations of 8-15 ng/mL from week 12 to week 39, and 5-10 ng/mL from week 39 to week 52.
Eligibility Criteria
You may qualify if:
- Receipt of a first cadaveric kidney graft
- Antilymphocyte antibodies and panel reactive antibodies (PRA) less than 30 percent (%) (historical peak and/or current value)
- Cold ischaemia time less than or equal to 36 hours
You may not qualify if:
- Kidney from a living donor; donor greater than (\>) 65 years of age; second renal graft, or more; or multiple organ transplant
- Known hypersensitivity to any of the drugs in the study or their components
- History of cancer or malignancy during previous 5 years, other than successfully treated spinocellular or basal cell cancer
- Participant with severe refractory hyperlipidaemia
- Pregnant woman or nursing mother
- Episode of acute rejection greater than or equal to grade I (Banff classification)
- Estimated creatinine clearance (CrCl) at week 12 less than (\<) 40 milliliter per minute (mL/min) (Cockcroft-Gault formula)
- Serum creatinine variations \>30% during the 15 days before randomization
- Proteinuria \>1 gram/24 hour, or mean mycophenolate mofetil dose \< 1.5 gram/day during the week before randomization
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
Unknown Facility
Angers, 49933, France
Unknown Facility
Caen, 14033, France
Unknown Facility
Clermont-Ferrand, 63000, France
Unknown Facility
La Tronche, 38700, France
Unknown Facility
Lille, 59037, France
Unknown Facility
Limoges, 87042, France
Unknown Facility
Lyon, 69437, France
Unknown Facility
Paris, 75018, France
Unknown Facility
Paris, 75475, France
Unknown Facility
Paris, 75743, France
Unknown Facility
Poitiers, 86021, France
Unknown Facility
Reims, 51092, France
Unknown Facility
Rennes, 35033, France
Unknown Facility
Rouen, 76031, France
Unknown Facility
Salouël, 80480, France
Unknown Facility
Strasbourg, 67091, France
Unknown Facility
Tours, 37044, France
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 16, 2016
First Posted
February 19, 2016
Study Start
November 1, 2004
Primary Completion
January 1, 2011
Study Completion
January 1, 2011
Last Updated
February 19, 2016
Record last verified: 2016-02