Efficacy and Safety of Everolimus+EC-MPS After Early CNI Elimination vs EC-MPS +Tacrolimus in Renal Transplant Recipients

NCT ID: NCT00965094

Last Updated: 2014-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2013-06-30

Brief Summary

The primary objective of this trial is to show non-inferiority of a CNI-free regimen with respect to the renal function at Month 9 post Tx assessed by glomerular filtration rate - Nankivell method - as compared to the standard CNI-based regimen in de novo renal transplant patients.

Conditions

Chronic Renal Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus

At BL1, all study patients received induction therapy with basiliximab (Simulect®; 2x20mg on day 0 - 2 hours prior to transplantation, and on day 4 after transplantation) and commenced an immunosuppressive regimen consisting of MPA (Myfortic®; target dose: 1440 mg/day, which was also the maximum daily dose) + tacrolimus (Prograf®; based on C0-h levels; Table 9-2) and with corticosteroids. AT BL2 \[Month 3 (+1 week) after transplantation\], eligible patients were randomized, using living and cadaveric donation as stratum. Patients were switched to the CNI-free regimen. Everolimus was added to the patients immunosuppressive regimen and tacrolimus was removed successively.

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

One tablet containing 0.25, 0.5mg or 0.75 mg. Initially 2 mg/day. Afterwards based on blood level (target 6-10 ng/mL)

Basiliximab

Intervention Type: DRUG

One vial containing 20 mg lyophilisate. 2 x 20 mg \[day 0 (2 hrs prior to Tx) and day 4 post Tx\] to be applied as 10 sec. bolus injection, i.v.

Enteric Coated Mycophenolate Sodium (EC-MPS)

Intervention Type: DRUG

One tablet containing 180 mg or 360 mg. 1440 mg/day (2x720 mg). If tolerated, dose reduction due to side effectis were possible (min. dose at BL@: 720 mg/day)

Corticosteroids

Intervention Type: DRUG

Used according to Israeli standards. A minimum dose of 5mg \[prednisone, or equivalent, was used throughout the study period.

Reference Therapy

At BL1, all study patients received induction therapy with basiliximab (Simulect®; 2x20mg on day 0 - 2 hours prior to transplantation, and on day 4 after transplantation) and commenced an immunosuppressive regimen consisting of MPA (Myfortic®; target dose: 1440 mg/day, which was also the maximum daily dose) + tacrolimus (Prograf®; based on C0-h levels; Table 9-2) and with corticosteroids. AT BL2 \[Month 3 (+1 week) after transplantation\], eligible patients were randomized, using living and cadaveric donation as stratum. Patients continued on the prior immunosuppressive regimen consisting of MPA + tacrolimus with corticosteroids.

Group Type: ACTIVE_COMPARATOR

Tacrolimus (FK506)

Intervention Type: DRUG

Capsules 0.5 mg, 1 mg. Dosing according to blood level.

Basiliximab

Intervention Type: DRUG

One vial containing 20 mg lyophilisate. 2 x 20 mg \[day 0 (2 hrs prior to Tx) and day 4 post Tx\] to be applied as 10 sec. bolus injection, i.v.

Enteric Coated Mycophenolate Sodium (EC-MPS)

Intervention Type: DRUG

One tablet containing 180 mg or 360 mg. 1440 mg/day (2x720 mg). If tolerated, dose reduction due to side effectis were possible (min. dose at BL@: 720 mg/day)

Corticosteroids

Intervention Type: DRUG

Used according to Israeli standards. A minimum dose of 5mg \[prednisone, or equivalent, was used throughout the study period.

Interventions

Everolimus

One tablet containing 0.25, 0.5mg or 0.75 mg. Initially 2 mg/day. Afterwards based on blood level (target 6-10 ng/mL)

Intervention Type: DRUG

Tacrolimus (FK506)

Capsules 0.5 mg, 1 mg. Dosing according to blood level.

Intervention Type: DRUG

Basiliximab

One vial containing 20 mg lyophilisate. 2 x 20 mg \[day 0 (2 hrs prior to Tx) and day 4 post Tx\] to be applied as 10 sec. bolus injection, i.v.

Intervention Type: DRUG

Enteric Coated Mycophenolate Sodium (EC-MPS)

One tablet containing 180 mg or 360 mg. 1440 mg/day (2x720 mg). If tolerated, dose reduction due to side effectis were possible (min. dose at BL@: 720 mg/day)

Intervention Type: DRUG

Corticosteroids

Used according to Israeli standards. A minimum dose of 5mg \[prednisone, or equivalent, was used throughout the study period.

Intervention Type: DRUG

Other Intervention Names

Certican; Prograf; Simulect; Myfortic

Eligibility Criteria

Inclusion Criteria

• Recipients of de novo cadaveric, living unrelated or living related kidney transplants
• Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at screening, 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.
• Patients who are willing and able to participate in the study and from whom written informed consent has been obtained.

Exclusion Criteria

• More than one previous renal transplantation
• Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
• Donor age: < 5 years or > 65 years
• Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
• Patients who had received an investigational drug within 4 weeks of the baseline period
• Patients who are recipients of A-B-O incompatible transplants or T cell cross-match positive transplants
• Patients with already existing antibodies against the HLA-type of the receiving transplant
• Patients with any known hypersensitivity to Simulect®, Certican®, mycophenolic acid, Prograf®, other drugs similar to Certican® (e.g., macrolides), or other components of the formulations.
• Patients who have received an investigational immunosuppressive drug within four weeks prior to study entry (Baseline visit 1)
• Patients with thrombocytopenia (platelets < 75,000/mm³), or an absolute neutrophil count of < 1,500/mm³ or leucopenia (leucocytes < 2,500/mm³), or hemoglobin < 6 g/dL
• Patients with preexisting lung disease (alveolitis, fibrosis) Patients with symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, who are unlikely to comply with the study requirements, or who are unable to give informed consent
• Patients with a history of malignancy during the last five years, except squamous or basal cell carcinoma of the skin
• Patients who are HIV positive or Hepatitis B surface antigen positive or Hepatitis C virus positive. Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C are excluded.
• Evidence of severe liver disease (incl. abnormal liver enzyme profile, i.e. AST, ALT or total bilirubin > 3 times UNL)
• Females of childbearing potential who are planning to become pregnant, who are pregnant or lactating, and/or who are unwilling to use effective means of contraception (see also section 8.2)
• Presence of a clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus that in the opinion of the investigator would interfere with the appropriate conduct of the study
• Evidence of drug or alcohol abuse
• Patients receiving drugs known to interact with Tacrolimus and/or everolimus according to the list provided in Appendix 3 to this protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Haifa, , Israel

Novartis Investigative Site

Petah Tikva, , Israel

Novartis Investigative Site

Tel Aviv, , Israel

Countries

Israel

References

Bemelman FJ, de Maar EF, Press RR, van Kan HJ, ten Berge IJ, Homan van der Heide JJ, de Fijter HW. Minimization of maintenance immunosuppression early after renal transplantation: an interim analysis. Transplantation. 2009 Aug 15;88(3):421-8. doi: 10.1097/TP.0b013e3181af1df6.

Reference Type: BACKGROUND

PMID: 19667948 (View on PubMed)

Other Identifiers

CRAD001AIL03

Identifier Type: -

Identifier Source: org_study_id