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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01596062
First received: September 29, 2011
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Renal Transplantation
Drug: Simulect®
Drug: Neoral®
Drug: Certican®
Drug: Myfortic®
Drug: Corticosteroids
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective, Multicenter, Randomized, Open-label, Phase 2, Lasting 12 Weeks, Evaluating the Pharmacodynamics, Efficacy and Safety of Basiliximab in de Novo Adult Renal Transplant Patients at Low Risk Receiving Either a Cumulative Dose of Basiliximab of 40 or 80 mg in Combination With Cyclosporine Microemulsion, or a Cumulative Dose of 80 mg of Basiliximab Without Calcineurin Inhibitor, With Additional Follow-up of 12 Weeks

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Area Under the Curve (AUC) of CD25 Saturation by Basiliximab From Day 0 to Day 84 [ Time Frame: Day 84 (Week 12) after transplantation ] [ Designated as safety issue: No ]
    CD25 saturation is the percentage of T cells expressing CD25. Mean AUC of CD25 was calculated only for patients who received two Simulect® injections.

  • Saturation Rate of CD25 Antigen Saturation by Basiliximab [ Time Frame: 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 ] [ Designated as safety issue: No ]
    CD25 saturation is the percentage of T cells expressing CD25


Secondary Outcome Measures:
  • AUC of Basiliximab Binding to CD25 Receptors From Day 0 to Day 84 [ Time Frame: Day 84 (Week 12) post-transplantation ] [ Designated as safety issue: No ]
    Mean AUC was calculated only for patients who received two Simulect injections.

  • Percentage of T-cells That Bind Basiliximab to CD25 Receptors [ Time Frame: 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 ] [ Designated as safety issue: No ]
    This is the percentage of T cells binding basiliximab at all timepoints.

  • Proportion of CD3+, CD4+, CD8+, CD19+ and CD56+ T Cells [ Time Frame: Day 0, Day 6, Day 42, Day 84 (Week 12) ] [ Designated as safety issue: No ]
    Cell counts of various subpopulations of T, B and NK lymphocytes (CD3, CD4, CD8, CD19 and CD56) (flow cytometry).

  • Percentage of Participants With of Biopsy Proven Acute Rejection (BPAR) [ Time Frame: Day 84 (Week 12), Week 24 post-transplantation ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 84 (Week 12), Week 24 post-transplantation ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With of Treatment Failures [ Time Frame: Day 84 (Week 12), Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 8, Week 24 ] [ Designated as safety issue: No ]
    (MDRDa formula) with imputation by last observation carried forward (LOCF)


Enrollment: 16
Study Start Date: March 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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
Drug: 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).
Other Name: Basiliximab
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.
Other Name: Cyclosporine microemulsion
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.
Other Name: mycophenolate sodium
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.
Experimental: Simulect 80mg + Neoral + Myfortic + steroids
A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Neoral® + Myfortic® + corticosteroids
Drug: 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).
Other Name: Basiliximab
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.
Other Name: Cyclosporine microemulsion
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.
Other Name: mycophenolate sodium
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.
Experimental: Simulect 80mg + Certican + Myfortic + steroids
A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Certican® + Myfortic® + corticosteroids
Drug: 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).
Other Name: Basiliximab
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.
Other Name: Everolimus
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.
Other Name: mycophenolate sodium
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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-)

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01596062

Locations
France
Novartis Investigative Site
Bordeaux Cedex, France, 33076
Novartis Investigative Site
Paris cedex 15, France, 75015
Novartis Investigative Site
Tours Cedex, France, 37044
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01596062     History of Changes
Obsolete Identifiers: NCT01469390
Other Study ID Numbers: CCHI621AFR05, 2010-024231-16
Study First Received: September 29, 2011
Results First Received: March 17, 2014
Last Updated: June 26, 2014
Health Authority: France: Conseil National de l'Ordre des Médecins
France: L'Agence nationale de sécurité du médicament et des produits de santé (ANSM)

Keywords provided by Novartis:
Basiliximab
renal transplantation
CNI-free
everolimus

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Mycophenolic Acid
Mycophenolate mofetil
Everolimus
Sirolimus
Basiliximab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on August 21, 2014