| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| CP-690,550 is an immunosuppressive agent being developed for the prevention of kidney allograft rejection, and for the treatment of rheumatoid arthritis as a disease-modifying anti-rheumatic drug. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10023439 |
| E.1.2 | Term | Kidney transplant rejection |
|
| 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 the incidence of clinical biopsy-proven acute rejection (BPAR) (as interpreted by the central blinded pathologist) of combination regimens of CP-690,550 and mycophenolate mofetil (MMF) / mycophenolate sodium (MPS) versus a cyclosporine (CsA)-based regimen in recipients of first renal allografts at Month 6 posttransplant To compare glomerular filtration rate (GFR), as measured by iohexol serum clearance, of combination regimens of CP-690,550 and MMF/MPS versus a CsA-based regimen at Month 12 posttransplant |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety and tolerability of combination regimens of CP-690,550 and MMF/MPS, including adverse events, clinically significant infections, malignancies, incidence and duration of delayed graft function, safety laboratory tests (including proteinuria), and estimated GFR (eGFR) (as calculated from equations); To compare GFR, as measured by iohexol serum clearance, of combination regimens of CP-690,550 and MMF/MPS versus a CsA-based regimen at Month 6 posttransplant; .To compare the progression of chronic allograft lesions of combination regimens of CP-690,550 and MMF/MPS versus a CsA-based regimen at Month 12 posttransplant; To evaluate the efficacy of combination regimens of CP-690,550 and MMF/MPS,including clinical BPAR at Month 12, treated clinical acute rejection combined Banff rejection categories, graft,loss,subject death and treatment failure To evaluate the PK of CP-690,550 and mycophenolic acid |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| 1. Subjects must have end-stage renal disease, have been on renal replacement therapy (eg, dialysis) for >/=1 month or have eGFR (estimated by the Cockcroft-Gault equation) </=10 mL/min, and are scheduled to receive a primary kidney transplant from a cadaveric donor, a living-related HLA-mismatched donor, or a living-unrelated HLA-mismatched donor; 2. Between the ages of 18 and 70 years, inclusive; 3. Either female (including women of childbearing potential) or male adults; 4. Subjects must have no known contraindications to the administration of IL-2 receptor antagonist induction, MMF, corticosteroids, or CsA; 5. Subjects must be willing and able to provide written informed consent with evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study; 6. Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
| 1. Subjects who have current PRA >30%, or who have undergone desensitization treatment; 2. Subjects who are recipients of or scheduled for non-renal transplants; 3. Subjects scheduled for double kidney transplantation; 4. Subjects with evidence of active infection; 5. Subjects with clinically significant infections within the past 3 months (eg, those requiring hospitalization, or as judged by the Investigator); 6. Subjects with a first-degree relative with a history of hereditary immunodeficiency (eg, severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, X-linked agammaglobinemia); 7. Subjects with a history of malignancies with the exception of excised non-metastatic basal cell carcinoma or squamous cell cancer of the skin, or adequately treated cervical carcinoma in situ (preinvasive). Subjects with a history of monoclonal gammopathy of undetermined significance (MGUS) will be excluded; 8. Subjects who have a history of allergy to iodine, betadine, iohexol or other iodinated contrast media; 9. Subjects who have a history of multiple allergies or severe allergy (eg, anaphylaxis) to any substance; 10. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of trial medication; 11. Subjects who are unwilling to refrain from consumption of grapefruit or grapefruit containing juices for the duration of trial medication period; 12. Subjects receiving or are expected to receive concomitant medications on the list of 13. Subjects with known positive results of the following serological tests: HIV-1 Ab, hepatitis B virus (HBV) surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab). Viral load monitoring (HBV DNA PCR and HCV RNA PCR) will be performed by the central laboratory on a blood sample collected prior to dosing of CP-690,550 or CsA to detect active infection. Positive results in these viral load tests will require subject discontinuation; 14. Subjects with mental dysfunction or inability to cooperate with the trial; 15. Subjects with the following laboratory parameters at screening: absolute neutrophil count (ANC) <1800/uL or hemoglobin (Hgb) <8 g/dL; 16. Subjects with any condition that may significantly affect drug absorption (eg, gastrectomy or insufficiently treated diabetic gastroenteropathy); 17. Body weight <90 lbs (<41 kg) or subjects who are morbidly obese at the time of transplant with a body mass index BMI >40 (Appendix B); 18. History of alcohol abuse with less than 6 months of sobriety, or history of drug abuse within the past 5 years;19. Males who are unwilling to abstain from sexual intercourse or use a condom with pregnant or lactating women. Non-vasectomized males unwilling to use a condom in addition to having their female partner use another form of contraception such as an IUD, diaphragm with spermicide, oral contraceptive, injectable progesterone, sub-dermal implant or a tubal ligation if the female partner could become pregnant from the time of the first dose of trial medication until completion of follow-up procedures; 20. Women of childbearing potential who are either pregnant, lactating, planning to become pregnant in the next 12 months, or with a positive serum or urine pregnancy test. Women of childbearing potential must be willing to agree to contraceptive practices; 21. Subjects with evidence of clinically significant disease (eg, gastrointestinal or hepatic disorders) that places the subject at increased risk for participating in the trial and/or will confound the results of the trial. prohibited medications (Appendix A); |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| First clinical BPAR episode (as interpreted by the central blinded pathologist) within 6 months posttransplant. Clinical BPAR is defined as a BPAR associated with an increase in serum creatinine of >/=0.3 mg/dL and >/=20% from pre-rejection baseline. GFR, measured by iohexol serum clearance, at Month 12. |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| parzialmente in doppio cieco, in aperto per lo sponsor |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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