First time recipient of a deceased donor liver transplant MedDRA version: 9.1 Level: LLT Classification code 10024714 Term: Liver transplant MedDRA version: 9.1 Level: LLT Classification code 10062016 Term: Immunosuppression
Conditions
Interventions
Product Name: BELATACEPT
Product Code: BMS-224818
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Belatacept
Current Sponsor code: BMS-224818
Other descriptive name: LEA29Y
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) The subject is willing to provide signed written informed consent 2) Target Population a) The subject is a first-time recipient of a deceased donor liver transplant 3) Age and Sex a) Men and women, ages 18 to 70 years, inclusive Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 56 days after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as: • Amenorrhea = 12 consecutive months without another cause or • For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level = 35 mIU/mL. Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. Women of child bearing potential taking MMF should be advised that per the US product information, "two reliable forms of contraception must be used simultaneously unless abstinence is the chosen method." WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product. Long-Term Extension (Protocol Amendment 3): 1) Signed Written Informed Consent 2) Target Population a) The subject has completed 1 year of study treatment (through Week 52) b) The subject is willing and able to continue therapy with their original assigned study medication (belatacept or tacrolimus) 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) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 56 days after the last dose of investigational product. b) Women who are pregnant or breastfeeding c) Women with a positive pregnancy test on enrollment or prior to investigational product administration. 2) Target Disease Exclusions Donor Exclusions a) Living donors b) ABO-incompatible donor recipient pairs c) Donor age 65 years d) Non heart-beating donors e) Anticipated cold ischemia time > 14 hours f) Donor Disease i) Known HIV infection ii) HBV surface antigen-positive or PCR-positive donor if HBV negative recipient iii) HCV antibody-positive or PCR positive donor if HCV negative recipient Recipient Exclusions g) Subjects with a history of hypercoagulable state h) Subjects with fulminant hepatic failure i) Subjects receiving a split or reduced liver j) Subjects who are EBV negative 3) Medical History and Concurrent Diseases a) Subjects who have received 2 or more consecutive weeks of dialysis 1 month prior to enrollment OR anticipated to have prolonged dialysis post-transplantation b) Subjects with known intrinsic renal disease (e.g., a urine protein/ creatinine ratio > 150 mg/g or the presence of an abnormal number of RBCs or granular casts in the urine) AND calculated GFR 3 cm in diameter ii) Non-melanoma skin cancers cured by local resection f) Subjects at risk for tuberculosis (TB). Specifically, subjects: i) With current clinical, radiographic, or laboratory evidence of active or latent TB as determined by local standard of care. ii) With history of active TB: (1) Within the last 2 years, even if it was treated (2) Greater than 2 years ago, unless there is documentation of adequate treatment according to locally accepted clinical practice iii) Who, in the opinion of the investigator and based upon appropriate evaluation, have a risk of reactivation of TB that precludes administration of conventional immunosuppression g) Subjects with any active infection or other contraindication that would normally exclude transplantation h) Subjects with active peptic ulcer disease, chronic diarrhea, or gastrointestinal malabsorption 4) Physical and Laboratory Test Findings a) Subjects with laboratory values that meet the following criteria are to be excluded from the study: i) Hemoglobin < 7 g/dL ii) White blood cell (WBC) count < 2000/mm³ (2 x 109/L) b) Subjects who have difficult intravenous access or other reasons that would likely preclude the ability to receive long-term intravenous infusions. c) Subjects with a chest radiograph consistent with an acute lung parenchymal process or malignancy. Subjects must have a chest radiograph no more than two months prior to enrollment. d) Subjects with a mammogram that is suspicious for malignancy. All women 50 years or o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effects of belatacept-based immunosuppression, relative to tacrolimus, on the incidence of AR (clinically suspected and biopsy-proven), graft loss and death by 6 months Long-Term Extension (Protocol Amendment 3): To assess the long-term safety and tolerability of a belatacept-based immunosuppressive regimen in subjects who have received a liver transplant and completed study treatment through week 52.;Secondary Objective: To evaluate the effects of belatacept, relative to tacrolimus, on: • The composite of subject and graft survival by 6 and 12 months • The triple composite of AR, graft loss and death by 12 months • Incidence, severity, treatment and outcome of AR by 3, 6 and 12 months • Change in renal function over time • Pharmacokinetic (PK) characteristics of belatacept • Incidence of HCV recurrence by 6 and 12 months • Incidence of metabolic and cardiovascular comorbidity (post-transplant diabetes mellitus [PTDM], dyslipidemia, hypertension) by 12 months • Overall safety Long-Term Extension (Protocol Amendment 3): To assess the above listed effects of belatacept, relative to tacrolimus, in the long-term treatment and to evaluate the incidence of discontinuation of study treatment.;Primary end point(s): Primary Efficacy Outcome Measure: • Triple composite of AR (clinically suspected and biopsy proven), graft loss and death by 6 months Secondary Efficacy Outcome Measures: • The composite of subject and graft survival by 6 and 12 months • The triple composite of AR, graft loss and death by 12 months • Incidence, severity, treatment and outcome of AR by 3, 6 and 12 months • Change in renal function over time • Pharmacokinetic (PK) characteristics of belatacept • Incidence of HCV recurrence by 6 and 12 months • Incidence of metabolic and cardiovascular comorbidity (post-transplant diabetes mellitus [PTDM], dyslipidemia, hypertension) by 12 months • Overall safety of belatacept based regimens Long-Term Exte | — |
Countries
Austria, France, Germany, Italy, Spain
Outcome results
None listed