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)
- Conditions
- Renal Transplantation
- Interventions
- Registration Number
- NCT01596062
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
- 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-)
Other protocol-defined inclusion/exclusion criteria may apply.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Simulect 80mg + Neoral + Myfortic + steroids Simulect® A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Neoral® + Myfortic® + corticosteroids Simulect 40mg + Neoral + Myfortic + steroids Myfortic® A cumulative dose of 40 mg of Simulect® (20mg at Day 0 (D0) and 20mg at Day 4 (D4)+ Neoral® + Myfortic® + corticosteroids Simulect 80mg + Neoral + Myfortic + steroids Myfortic® A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Neoral® + Myfortic® + corticosteroids Simulect 80mg + Certican + Myfortic + steroids Myfortic® A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Certican® + Myfortic® + corticosteroids Simulect 40mg + Neoral + Myfortic + steroids Simulect® A cumulative dose of 40 mg of Simulect® (20mg at Day 0 (D0) and 20mg at Day 4 (D4)+ Neoral® + Myfortic® + corticosteroids Simulect 80mg + Certican + Myfortic + steroids Simulect® A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Certican® + Myfortic® + corticosteroids Simulect 40mg + Neoral + Myfortic + steroids Neoral® A cumulative dose of 40 mg of Simulect® (20mg at Day 0 (D0) and 20mg at Day 4 (D4)+ Neoral® + Myfortic® + corticosteroids Simulect 40mg + Neoral + Myfortic + steroids Corticosteroids A cumulative dose of 40 mg of Simulect® (20mg at Day 0 (D0) and 20mg at Day 4 (D4)+ Neoral® + Myfortic® + corticosteroids Simulect 80mg + Certican + Myfortic + steroids Certican® A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Certican® + Myfortic® + corticosteroids Simulect 80mg + Neoral + Myfortic + steroids Corticosteroids A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Neoral® + Myfortic® + corticosteroids Simulect 80mg + Neoral + Myfortic + steroids Neoral® A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Neoral® + Myfortic® + corticosteroids Simulect 80mg + Certican + Myfortic + steroids Corticosteroids A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Certican® + Myfortic® + corticosteroids
- Primary Outcome Measures
Name Time Method Saturation Rate of CD25 Antigen Saturation by Basiliximab Day 0, Day 1, Day 4, Day 6, Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84 (Week 12) post-transplantation CD25 saturation is the percentage of T cells expressing CD25
Area Under the Curve (AUC) of CD25 Saturation by Basiliximab From Day 0 to Day 84 Day 84 (Week 12) after transplantation CD25 saturation is the percentage of T cells expressing CD25. Mean AUC of CD25 was calculated only for patients who received two Simulect® injections.
- Secondary Outcome Measures
Name Time Method AUC of Basiliximab Binding to CD25 Receptors From Day 0 to Day 84 Day 84 (Week 12) post-transplantation Mean AUC was calculated only for patients who received two Simulect injections.
Percentage of T-cells That Bind Basiliximab to CD25 Receptors Day 0, Day 1, Day 4, Day 6, Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84 (Week 12) post-transplantation This is the percentage of T cells binding basiliximab at all timepoints.
Percentage of Participants With of Treatment Failures Day 84 (Week 12), Week 24 Treatment failure was defined either as a BPAR, a graft loss, a death or a loss to follow-up. An extended treatment failure was also defined including treated borderline lesions, BPAR, graft loss, death or loss to follow-up. Treated borderline lesions were considered as acute rejection by investigators and DMC experts.
Estimated Glomerular Filtration Rate (eGFR) at Day 8 and Week 24 Day 8, Week 24 (MDRDa formula) with imputation by last observation carried forward (LOCF)
Percentage of Participants With of Biopsy Proven Acute Rejection (BPAR) Day 84 (Week 12), Week 24 post-transplantation BPAR is one of the components of treatment failure. One assessment of efficacy was BPAR. Renal graft biopsies were performed and the renal tissue was examined to determine if there was acute rejection of the renal transplant.
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR) According to Type and Severity Day 84 (Week 12), Week 24 post-transplantation Antibody mediated acute rejection: C4d deposition, presence of circulating antidonor antibody, morphologic evidence of acute tissue injury such as acute tubular necrosis-like minimal inflammation or capillary and/or glomerular inflammation and/or thromboses or arterial inflammation. Cellular acute rejection: acute T-cell mediated rejection Type IA: Significant interstitial infiltration (\> 25% of parenchyma) and foci of moderate tubulitis (\> 4 mononuclear cells/tubular cross section or group of 10 tubular cells) Type IB: Significant interstitial infiltration (\> 25% of parenchyma) and foci of severe tubulitis (\> 10 mononuclear cells/tubular cross section or group of 10 tubular cells) Type IIA: Mild to moderate intimal arteritis. Type IIB: Severe intimal arteritis comprising \> 25% of the lumenal area. Type III: Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation).
Proportion of CD3+, CD4+, CD8+, CD19+ and CD56+ T Cells Day 0, Day 6, Day 42, Day 84 (Week 12) Cell counts of various subpopulations of T, B and NK lymphocytes (CD3, CD4, CD8, CD19 and CD56) (flow cytometry).
Trial Locations
- Locations (1)
Novartis Investigative Site
🇫🇷Tours Cedex, France