A multi-centre trial of a new immunosuppression regime for pancreatic islet transplant recipients

Exclusion Criteria46

• WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study medication. It should be noted that according to the US product information for mycophenolate mofetil (CellCept©) and mycophenolic acid (Myfortic©), “two reliable forms of contraception be used simultaneously unless abstinence is the chosen method”
• WOCBP using a prohibited contraceptive method
• Women who are pregnant or breastfeeding
• Women with a positive pregnancy test on enrolment or prior to study drug administration
• Subjects who had a positive T-cell or B-cell crossmatch
• Subjects with a prior solid organ (kidney, heart, liver, pancreas) or cell ( bone marrow, stem cell) transplants
• Subjects who are known hepatitis C antibody-positive or PCR-positive for hepatitisC (neither hepatitis C antibody or PCR for hepatitis C testing is required for entry into the study)
• Subjects who are known hepatitis B surface antigen-positive or PCR-positive for hepatitis B (neither hepatitis B surface antigen or PCR for hepatitis B testing is required for entry into the study)
• Subjects with known human immunodeficiency virus (HIV) infection. HIV testing is not required for entry into the study
• Subjects with a chest radiograph (posterior-anterior and lateral views) consistent with an acute lung parenchymal process, malignancy, or active tuberculosis. Subjects must have a chest radiograph within 2 months prior to transplantation
• Subjects with any significant infection
• Baseline LFT's outside of normal range
• Insulin requirement > 0.7 IU/kg/day or a HbA1c > 12%
• Serum Cholesterol > 10 mmol/l
• Requirement for systemic corticosteroid usage
• Treatment with terfenadine, cisapride, astemizole, pimozide, or ketoconazole (that is not discontinued prior to sirolimus administration).
• Malignant disease other than localized and excised skin Squamous Cell or Basal Cell Carcinoma
• Hepatic disease, including any form of active viral hepatitis, portal venous abnormality or cirrhosis
• Chronic Pancreatitis
• Significant cardiac disease including ischaemic and valvular heart disease
• Respiratory disease including clinically significant asthma, bronchiectasis or obstructive airways disease.
• Any form of chronic or current acute mental or psychiatric illness that in the opinion of the investigator would prevent them from adhering to the trial protocol
• Any form of chronic infection that could in the view of the investigator pose a risk after transplantation
• Allergy to intravenous contrast agents, sirolimus, belatacept or anti-thymocyte globulin
• Subjects whose life expectancy is severely limited by disease state or other underlying medical condition
• Subjects with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years
• Subjects with a history of substance abuse (drug or alcohol) within the past 5 years, or psychotic disorders that are not compatible with adequate study follow-up
• Any other disease which in the opinion of the investigator may represent a significant risk after transplantation and immunosuppression
• Subjects with laboratory values that meet the following criteria are to be excluded from the study:
• Urine Assay:
• a) Proteinuria > 300 mg/day or
• b) Urine protein : creatinine ratio > 1
• Hematology:
• a) Hemoglobin < 7 g/dL
• b) Platelets < 80,000/mm3
• c) White blood cell count < 3000/mm3 (3 x 109/L)
• Chemistry:
• a) Bilirubin >1.5 x upper limit of normal range (ULN); Subjects who have Gilbert’s syndrome and have a normal direct bilirubin are permitted
• b) Aspartate aminotransferase (AST) greater than or equal to 2 x ULN
• c) Alanine aminotransferase (ALT) greater than or equal to 2 x ULN
• All women 50 years or older must have a screening mammogram or provide results of a mammogram performed within 6 months of enrolment. Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical or diagnostic evaluations will be excluded. Women of any age who have a first degree relative with a history of breast cancer or who have other risk factors for breast cancer must undergo increased surveillance for breast cancer according to local practice.
• Subjects who have difficult i.v. access
• Subjects who have used any investigational drug within 30 days prior to the Day 1 visit
• Subjects previously treated with belatacept
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
• Subjects previously treated with belatacept or previously enrolled in a belatacept trial with their present allograft