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 evaluate the efficacy of sirolimus assessed by the incidence of biopsy-confirmed acute rejection episode at 6 months after transplantation in Korean renal transplantation recipients. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of sirolimus over 12 months after transplantation in Korean renal transplantation recipients.
To evaluate graft function, subject survival and graft survival at 6, 12 months after transplantation, and biopy confirmed acute rejection rate within 12 months after transplantation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age great than (>) 13 years
2. End-stage renal disease, with subjects receiving a primary renal allograft from a cadaveric donor, from a living-unrelated donor, or from a living-related (excluding 0 antigen mismatch) donor. A mismatch is defined as a donor human leukocyte antigen (HLA) antigen not shared by the patient.
3. All female subjects at risk for pregnancy must have a negative pregnancy test result before sirolimus administration, and must agree and commit to the use of a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation of study medication. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Any female subject who becomes pregnant during the treatment period must be discontinued from the on-therapy portion of the study.
4. Total white blood cell count greater than or equal to (>=) 4,000/ cubic millimeter (mm^3) (4.0 *10^9 /liter [L]), platelet count >= 100,000/mm^3 (100 x 10 9/L, fasting triglycerides >=400 milligram per deciliter (mg/dL), and fasting cholesterol >= 300 mg/dl. If it is not possible to obtain fasting triglycerides and cholesterol before surgery, historical values less than (<) 1 year may be used.
5. Signed and dated informed consent (parent or legal guardian must provide consent for patients <18 years of age). If possible, an assent form will be signed by patients <18 years of age enrolled in the study.
6. Patients with a panel of reactive antibody (%PRA) less than equal to (<=) 50 percent (%).
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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. Evidence of infiltration, cavitation, or consolidation on chest x-ray obtained during pre-study screening
3. Chronic antiarrhythmic therapy for ventricular arrhythmia or other cardiac abnormality contraindicating general anesthesia or surgery
4. 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).
5. Use of any investigational drug during the 4 weeks before enrolling in the study.
6. Presence of 4 or more HLA mismatches.
7. Active gastrointestinal disorder that may interfere with drug absorption.
8. Known hypersensitivity to sirolimus or its derivatives.
9. Multiple organ transplants
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of subjects experiencing biopsy confirmed acute rejection through month 6 after transplantation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after transplantation |
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E.5.2 | Secondary end point(s) |
1) Glomerular Filtration Rate (GFR) (Nankivell Method)
2) Serum Creatinine
3) Subject and Graft Survival
4) Number of subjects Experiencing Biopsy Confirmed Acute Rejection Through Month 12 After Transplantation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 6 and 12 months
2) Baseline, 6 and 12 months
3) 12 months
4) 12 months after transplantation |
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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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 |
Korea, Democratic People's 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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 5 |