E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038533 |
E.1.2 | Term | Renal transplant |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare incidence of biopsy-confirmed acute rejection, graft loss, or death within 12 months post-transplantation between the treatment arm A (CsA+Rapamune+CS) and treatment arm B (CsA+MMF+CS). |
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E.2.2 | Secondary objectives of the trial |
To compare serum creatinine at 3, 6 and 12 months after transplantation.
To compare Glomerular Filtration Rate (GFR) (Nankivell method) at 3, 6 and 12 months after transplantation.
To compare incidence of biopsy-confirmed acute rejection at 6 months following transplantation.
To compare histologic grade of first acute rejection.
To compare subject and graft survival at 12 months after transplantation.
To compare incidence of infections, histologically-confirmed lymphoproliferative disease and anemia at 12 months after transplantation.
To compare incidence of efficacy failure or treatment failure.
To compare number of subjects discontinuing assigned therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age greater than or equal to (>=) 13 years and weight >=40 kg.
2. End-stage renal disease, with subjects receiving a primary or secondary renal allograft from a living-unrelated donor, or from a living-related donor.
3. Women who are of childbearing potential must have a negative pregnancy test before enrollment in the study and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation from the study.
4. Total white blood cell count >= 4.0 x 109/ Liter (L) (4,000/millimeter (mm) P^3) platelet count ≥ 100 x 10^9/L (100,000/mm ^3), fasting triglycerides greater than or equal to <=4.6 miliimole per liter (mmol/L) (400 milligram per deciliter [mg/dL]), fasting cholesterol <= 7.8 mmol/L (300 mg/dL). If it is not possible to obtain fasting triglycerides and cholesterol before surgery, historical values (within 1 year) may be used.
5. Signed and dated informed consent (parent or legal guardian must provide consent for subjects less than (<) 18 years of age). An assent form will be signed by subjects < 18 years of age enrolled in the study. |
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E.4 | Principal exclusion criteria |
1. Evidence of active systemic or localized major infection at the time of initial Sirolimus administration.
2. Cadaveric donors
3. History of malignancy within 5 years before enrollment into the study (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin)
4. Use of any investigational drug other than specified in the protocol during the 4 weeks before enrolling in the study.
5. Use of planned antibody induction therapy at the time of transplantation.
6. Active gastrointestinal disorder that may interfere with drug absorption.
7. Known hypersensitivity to Sirolimus, Mycophenolat Mofetil (MMF) or Cyclosporine or its derivatives.
8. Multiple organ transplants (2 or more organ transplant e.g. Kidney and Pancreas).
9. Subject with high risk of rejection (eg. subjects with a PRA greater than (>) 50 percent (%), black subjects and subjects with 2nd transplant who lost their first graft within the first 6 months).
10. Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during pre-study screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of Efficacy Failure
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Serum Creatinine Level
2. Creatinine Clearance
3. Glomerular Filtration Rate (GFR) by Nankivell Method
4. Incidence of Biopsy-Confirmed Acute Rejection
5. Histologic Grade of First Acute Rejection
6. Percentage of subjects Who Survived
7. Percentage of subjects With Graft Survival
8. Incidence of Presumptive or Documented Infection
9. Incidence of Histologically Confirmed Lymphoproliferative Disease
10. Percentage of Subjects With Efficacy Failure or Premature Elimination
11. Incidence of Anemia
12. Number of Subjects Who Discontinued
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Month 3, 6, 12
2. Month 3, 6, 12
3. Month 3, 6, 12
4. Baseline up to Month 6
5. Baseline up to Month 12
6. Month 12
7. Month 12
8. Baseline up to Month 12
9. Baseline up to Month 12
10. Month 12
11. Baseline up to Month 12
12. Month 12
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Iran, Islamic Republic of |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 24 |