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

Renal Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02686619
• Other study ID #: ML18326
• Status: Completed
• Phase: Phase 3
• First received: February 16, 2016
• Last updated: February 16, 2016
• Start date: November 2004
• Est. completion date: January 2011

Study information

• Verified date: February 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps Agence française de sécurité sanitaire des produits de santé (SaintDenis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 237
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 presenting, on inclusion, either symptoms suggestive of active gastroduodenal ulcer, or gastroduodenal ulcer confirmed by fibroscopy and biopsy, and requiring treatment

• Participant with severe refractory hyperlipidaemia

• Pregnant woman or nursing mother

Exclusion Criteria for Follow-up Phase:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Drug:
• Cyclosporine
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
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
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
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
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Month 60		60 months	No
Primary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to approximately 12 months	No
Primary	Number of Participants With Serious Adverse Events (SAEs)		From 12 months up to 60 months	No
Primary	Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Week 52		52 weeks	No
Primary	Number of Participants With Cancers and Lymphoproliferative Syndromes		Up to approximately 12 months	No
Primary	Number of Participants With Premature Discontinuations due to Adverse Events (AEs)		Up to approximately 12 months	No
Primary	Change From Baseline in 24-Hour Urinary Protein at Week 52		52 weeks	No
Secondary	Mean Inverse Creatinine Concentration		Week 4, 8, 12, 14, 16, 26, 39, and 52	No
Secondary	Creatinine Clearance Calculated and Corrected According to Cockcroft-Gault		Week 4, 8, 12, 14, 16, 26, 39, and 52	No
Secondary	Glomerular Filtration Rate (GFR) Measured by Iohexol Clearance		Baseline, Week 52	No
Secondary	Number of Participants with Response to Treatment, Defined as Creatinine Clearance >/=60 mL/min at Week 52		Week 52	No
Secondary	Number of Participants With Treated Rejections		Baseline up to Week 52	No
Secondary	Mean Serum Creatinine Concentration		Week 4, 8, 12, 14, 16, 26, 39, and 52	No
Secondary	Number of Participants With Biopsy-proven Acute Rejections		Baseline up to Month 60	No
Secondary	Number of Participants With Histologic Evaluation of the Graft		Week 52	No
Secondary	Number of Participants Who Were Alive		Month 60	No
Secondary	Number of Participants With Graft Survival		Month 60	No