Pharmacodynamics, Efficacy and Safety of Basiliximab 40 or 80 mg in Combination With Ciclosporine Microemulsion or Everolimus, in Adult Low Risk de Novo Renal Transplant Recipients (IDEALE Study)

NCT ID: NCT01596062

Last Updated: 2014-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2013-03-31

Brief Summary

The aims of this study are to extensively study the levels of CD25-Receptors saturation and expression obtained with 2 different doses of Simulect® in combination with Neoral® (i.e to demonstrate that saturation and expression vary according to the dose of Simulect® given), and to study the levels of CD25-Receptors saturation without Neoral® and compare them to the data with Neoral®.

It will be conducted in low risk de novo adult renal transplant recipients until 12 weeks post-transplant, receiving either a cumulative dose of 40 or 80 mg of Simulect® in combination with Neoral®, or a cumulative dose of 80 mg of Simulect® in a calcineurin inhibitor free immunosuppressant therapy.

Conditions

Renal Transplantation

Study Design

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

Study Groups

Simulect 40mg + Neoral + Myfortic + steroids

A cumulative dose of 40 mg of Simulect® (20mg at Day 0 (D0) and 20mg at Day 4 (D4)+ Neoral® + Myfortic® + corticosteroids

Group Type: ACTIVE_COMPARATOR

Simulect®

Intervention Type: DRUG

Simulect® was provided to the study center in its commercial package containing a powder vial with 20 mg of active product and sterile water for injection. The solution should be used immediately after reconstitution. The infusion was prepared by adding at least 50 mL of physiologic or 5% glucose solution to the reconstituted solution (at least 100 mL for 40 mg of Simulect®). Simulect® was transported and kept in a cold environment (2-8°C) as recommended in the summary of product characteristics (SPC).

Neoral®

Intervention Type: DRUG

Neoral® was provided to the study center in its commercial package as 10, 25, 50 or 100 mg soft capsules in thermoformed blister packs.

Myfortic®

Intervention Type: DRUG

Myfortic® was administered orally b.i.d. with a 12-hour interval. Tablets could be taken either with or outside meals but consistently throughout the study. To maintain the integrity of the enteric coating, tablets were not to be crushed. Myfortic® treatment was initiated either preoperatively or within 24 hours post transplantation according to local practice in each center. Starting dose was to be 2160 mg/day (1080 mg b.i.d.) for at least 2 weeks and for at most 4 weeks. Patients were then to receive 1440 mg/day (720 mg b.i.d.) until the end of the study. Myfortic® was administered as concomitant treatment to all patients, using the same regimen for all 3 study groups. It was provided to the study center in its commercial package as 180 and 360 mg gastro-resistant tablets.

Corticosteroids

Intervention Type: DRUG

Corticosteroid i.v. therapy could be administered peri or per operatively according to local practice in each center with the same scheme for each patient in the center. Oral corticotherapy was to be initiated rapidly, within one week following transplantation, with a minimal dose of 20 mg/day. Thereafter, the dose was to be decreased according to local practice but oral corticosteroids were to be continued throughout the study with a minimal dose of 5 mg/day.

Simulect 80mg + Neoral + Myfortic + steroids

A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Neoral® + Myfortic® + corticosteroids

Group Type: EXPERIMENTAL

Simulect®

Intervention Type: DRUG

Simulect® was provided to the study center in its commercial package containing a powder vial with 20 mg of active product and sterile water for injection. The solution should be used immediately after reconstitution. The infusion was prepared by adding at least 50 mL of physiologic or 5% glucose solution to the reconstituted solution (at least 100 mL for 40 mg of Simulect®). Simulect® was transported and kept in a cold environment (2-8°C) as recommended in the summary of product characteristics (SPC).

Neoral®

Intervention Type: DRUG

Neoral® was provided to the study center in its commercial package as 10, 25, 50 or 100 mg soft capsules in thermoformed blister packs.

Myfortic®

Intervention Type: DRUG

Myfortic® was administered orally b.i.d. with a 12-hour interval. Tablets could be taken either with or outside meals but consistently throughout the study. To maintain the integrity of the enteric coating, tablets were not to be crushed. Myfortic® treatment was initiated either preoperatively or within 24 hours post transplantation according to local practice in each center. Starting dose was to be 2160 mg/day (1080 mg b.i.d.) for at least 2 weeks and for at most 4 weeks. Patients were then to receive 1440 mg/day (720 mg b.i.d.) until the end of the study. Myfortic® was administered as concomitant treatment to all patients, using the same regimen for all 3 study groups. It was provided to the study center in its commercial package as 180 and 360 mg gastro-resistant tablets.

Corticosteroids

Intervention Type: DRUG

Corticosteroid i.v. therapy could be administered peri or per operatively according to local practice in each center with the same scheme for each patient in the center. Oral corticotherapy was to be initiated rapidly, within one week following transplantation, with a minimal dose of 20 mg/day. Thereafter, the dose was to be decreased according to local practice but oral corticosteroids were to be continued throughout the study with a minimal dose of 5 mg/day.

Simulect 80mg + Certican + Myfortic + steroids

A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Certican® + Myfortic® + corticosteroids

Group Type: EXPERIMENTAL

Simulect®

Intervention Type: DRUG

Simulect® was provided to the study center in its commercial package containing a powder vial with 20 mg of active product and sterile water for injection. The solution should be used immediately after reconstitution. The infusion was prepared by adding at least 50 mL of physiologic or 5% glucose solution to the reconstituted solution (at least 100 mL for 40 mg of Simulect®). Simulect® was transported and kept in a cold environment (2-8°C) as recommended in the summary of product characteristics (SPC).

Certican®

Intervention Type: DRUG

Certican® was provided to the study center in its commercial package as 0.75, 0.5 and 0.25 mg tablets in thermoformed blister packs.

Myfortic®

Intervention Type: DRUG

Myfortic® was administered orally b.i.d. with a 12-hour interval. Tablets could be taken either with or outside meals but consistently throughout the study. To maintain the integrity of the enteric coating, tablets were not to be crushed. Myfortic® treatment was initiated either preoperatively or within 24 hours post transplantation according to local practice in each center. Starting dose was to be 2160 mg/day (1080 mg b.i.d.) for at least 2 weeks and for at most 4 weeks. Patients were then to receive 1440 mg/day (720 mg b.i.d.) until the end of the study. Myfortic® was administered as concomitant treatment to all patients, using the same regimen for all 3 study groups. It was provided to the study center in its commercial package as 180 and 360 mg gastro-resistant tablets.

Corticosteroids

Intervention Type: DRUG

Corticosteroid i.v. therapy could be administered peri or per operatively according to local practice in each center with the same scheme for each patient in the center. Oral corticotherapy was to be initiated rapidly, within one week following transplantation, with a minimal dose of 20 mg/day. Thereafter, the dose was to be decreased according to local practice but oral corticosteroids were to be continued throughout the study with a minimal dose of 5 mg/day.

Interventions

Simulect®

Simulect® was provided to the study center in its commercial package containing a powder vial with 20 mg of active product and sterile water for injection. The solution should be used immediately after reconstitution. The infusion was prepared by adding at least 50 mL of physiologic or 5% glucose solution to the reconstituted solution (at least 100 mL for 40 mg of Simulect®). Simulect® was transported and kept in a cold environment (2-8°C) as recommended in the summary of product characteristics (SPC).

Intervention Type: DRUG

Neoral®

Neoral® was provided to the study center in its commercial package as 10, 25, 50 or 100 mg soft capsules in thermoformed blister packs.

Intervention Type: DRUG

Certican®

Certican® was provided to the study center in its commercial package as 0.75, 0.5 and 0.25 mg tablets in thermoformed blister packs.

Intervention Type: DRUG

Myfortic®

Myfortic® was administered orally b.i.d. with a 12-hour interval. Tablets could be taken either with or outside meals but consistently throughout the study. To maintain the integrity of the enteric coating, tablets were not to be crushed. Myfortic® treatment was initiated either preoperatively or within 24 hours post transplantation according to local practice in each center. Starting dose was to be 2160 mg/day (1080 mg b.i.d.) for at least 2 weeks and for at most 4 weeks. Patients were then to receive 1440 mg/day (720 mg b.i.d.) until the end of the study. Myfortic® was administered as concomitant treatment to all patients, using the same regimen for all 3 study groups. It was provided to the study center in its commercial package as 180 and 360 mg gastro-resistant tablets.

Intervention Type: DRUG

Corticosteroids

Corticosteroid i.v. therapy could be administered peri or per operatively according to local practice in each center with the same scheme for each patient in the center. Oral corticotherapy was to be initiated rapidly, within one week following transplantation, with a minimal dose of 20 mg/day. Thereafter, the dose was to be decreased according to local practice but oral corticosteroids were to be continued throughout the study with a minimal dose of 5 mg/day.

Intervention Type: DRUG

Other Intervention Names

Basiliximab; Cyclosporine microemulsion; Everolimus; mycophenolate sodium

Eligibility Criteria

Inclusion Criteria

• Patients receiving a primary renal graft from a deceased or living, related or unrelated donor and who require basiliximab induction therapy
• Cold ischemia time < 30 hours

Exclusion (Non inclusion) criteria:

• Patients undergoing multi-organ transplantation, including both kidneys, or who have previously undergone organ transplantation, including renal transplantation
• Patients receiving a graft from a non-heart-beating donor
• A-B-O incompatible graft or positive T cell crossmatch
• Patients receiving a graft from an expanded criteria donor according to the UNOS definition (donor older than 60 years or donor aged between 50 and 60 years and presence of at least 2 of the following factors: hypertension, serum creatinine concentration ≥ 132 µmol/mL, cardiovascular cause of death)
• Positive anti-HLA antibodies (Luminex) prior to transplantation
• Patients whose original renal disease was primary focal and segmental hyalinosis or was related to atypical hemolytic uremic syndrome
• EBV-negative patients receiving a graft from an EBV-positive donor (EBV D+R-)

• 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 Pharmaceticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Bordeaux, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Tours, , France

Countries

France

References

Thibault G, Paintaud G, Legendre C, Merville P, Coulon M, Chasseuil E, Ternant D, Rostaing L, Durrbach A, Di Giambattista F, Buchler M, Lebranchu Y. CD25 blockade in kidney transplant patients randomized to standard-dose or high-dose basiliximab with cyclosporine, or high-dose basiliximab in a calcineurin inhibitor-free regimen. Transpl Int. 2016 Feb;29(2):184-95. doi: 10.1111/tri.12688. Epub 2015 Oct 8.

Reference Type: DERIVED

PMID: 26369526 (View on PubMed)

Other Identifiers

2010-024231-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CCHI621AFR05

Identifier Type: -

Identifier Source: org_study_id

NCT01469390

Identifier Type: -

Identifier Source: nct_alias