Efficacy and Safety of Everolimus With Enteric-Coated Mycophenolate Sodium (EC-MPS) in a Cyclosporine Microemulsion-free Regimen Compared to Standard Therapy in de Novo Renal Transplant Patients

Novartis

Status and phase: Completed; Phase 4

Conditions: Renal Transplantation

Treatments: Drug: Cyclosporine; Drug: Everolimus; Drug: Enteric-coated mycophenolate sodium; Drug: Corticosteroids

Study type: Interventional

Funder types: Industry

Identifiers

NCT00154310

CRAD001A2418

Details and patient eligibility

About

The purpose of this study is to assess whether a calcineurin inhibitor (CNI)-free regimen with enteric-coated mycophenolate sodium (EC-MPS) and everolimus is as safe and well-tolerated as the standard regimen containing enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion, but results in better renal function.

Enrollment: 300 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria :

The following inclusion criteria had to be present at BL 1 (Screening visit prior to transplantation):

1. Males or females, aged 18 - 65 years

2. Recipients of de novo cadaveric, living unrelated or living related kidney transplants

3. Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at BL 1, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility

4. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained

   Of all patients included into the study at BL 1 (prior to transplantation), those who continued into the randomized study period had to meet the following condition at BL 2, prior to randomization:

5. Patients had to be on an immunosuppressive regimen with EC-MPS (target dose; 1440 mg/day, if tolerated; minimal dose: 720 mg/day), cyclosporine and corticosteroids

6. Patients with an actual serum creatinine =< 3.0 mg/dl

Exclusion Criteria:

The following exclusion criteria must not be present at BL 1 (Screening visit prior to transplantation):

1. More than one previous renal transplantation

2. Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney

3. Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)

4. Patients who are recipients of A-B-O incompatible transplants

5. Patients with a historical or current peak PRA of > 25%

6. Patients with already existing antibodies against the HLA-type of the receiving transplant

7. Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception

   Of all patients included into the study at BL 1 (prior to transplantation), those who met one or more of the following criteria at BL 2, prior to randomization, should not continue into the randomized study period:

8. Graft loss or death

9. Changes to the immunosuppressive regimen prior to randomization due to immunologic reasons

10. Patients who suffered from severe rejection (>= BANFF II acute rejection), recurrent acute rejection, or steroid resistant acute rejection

11. Proteinuria > 1g/day

Other protocol-defined exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

300 participants in 2 patient groups

Everolimus + Mycophenolate sodium

Experimental group

Description:

Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.

Treatment:

Drug: Corticosteroids

Drug: Enteric-coated mycophenolate sodium

Drug: Everolimus

Cyclosporine + Mycophenolate sodium

Active Comparator group

Description:

Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.

Treatment:

Drug: Corticosteroids

Drug: Enteric-coated mycophenolate sodium

Drug: Cyclosporine