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

Roche

Status and phase: Completed; Phase 3

Conditions: Renal Transplantation

Treatments: Drug: Mycophenoate Mofetil; Drug: Prednisolone; Drug: Daclizumab; Drug: Cyclosporine; Drug: Sirolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT02686619

ML18326

Details and patient eligibility

About

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.

Enrollment: 237 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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237 participants in 2 patient groups

Mycophenolate Mofetil + Cyclosporine

Active Comparator group

Description:

Participants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months.

Treatment:

Drug: Cyclosporine

Drug: Daclizumab

Drug: Prednisolone

Drug: Mycophenoate Mofetil

Mycophenolate Mofetil + Sirolimus

Experimental group

Description:

Participants 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.

Treatment:

Drug: Sirolimus

Drug: Cyclosporine

Drug: Daclizumab

Drug: Prednisolone

Drug: Mycophenoate Mofetil