Prevention of kidney allograft rejection MedDRA version: 9.1 Level: LLT Classification code 10066543 Term: Acute allograft rejection
Conditions
Interventions
Product Name: CP-690,550
Pharmaceutical Form: Tablet
CAS Number: 540737-29-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Current Sponsor code: CP-690,550
Pha
Sponsors
Pfizer Inc. 235 East 42nd Street, New York, NY10017
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 prohibited medications (Appendix A); 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) 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 pla
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) 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 2) 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;Secondary Objective: 1) 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 and estimated GFR. 2) To compare GFR, as measured by iohexol serum clearance, of combination regimens of CP-690,550 and MMF/MPS vs a CsA-based regimen at Month 6 posttransplant 3) 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 4) 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 5) To evaluate the PK of CP-690,550 and mycophenolic acid 6) To evaluate the effects of CP-690,550 on lymphocyte subsets and on health outcome assessment;Primary end point(s): 1) 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. 2) GFR, measured by iohexol serum clearance, at Month 12. | — |
Countries
Belgium, Czech Republic, France, Germany, Italy, Netherlands, Portugal, Spain
Outcome results
None listed