临床试验/NCT00555321

NCT00555321终止2 期

Evaluation of Belatacept as First Line Immunosuppression in De Novo Liver Transplant Recipients

Bristol-Myers Squibb20 个研究点分布在 2 个国家目标入组 260 人开始时间: 2008年1月最近更新: 2012年10月18日

适应症

干预措施

试验速览

阶段: 2 期
状态: 终止
发起方
入组人数: 260
试验地点: 20
主要终点: Percentage of Participants Who Experienced at Least One Episode of Acute Rejection (AR), Graft Loss, or Death by 6 Months Post-transplant

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this clinical research study is to evaluate the effects of belatacept, relative to tacrolimus, on the incidence of rejection, graft loss and death in subjects receiving a liver transplant

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Prevention
盲法: None

入排标准

年龄范围: 18 Years 至 70 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•First time recipient of deceased donor liver transplant
•Age 18-70
•Hepatitis C virus (HCV) positive recipients
•For Long-term extension study-Subjects who have completed one year of study treatment (through Week 52)
•Target Disease Exclusions:
•Donor Exclusions a) Living donors b) ABO-incompatible donor recipient pairs c) Donor age < 12 or > 65 years d) Non heart-beating donors e) Anticipated cold ischemia time > 14 hours f) Donor Disease i) Known Human immunodeficiency virus (HIV) infection ii) Hepatitis B virus (HBV) surface antigen-positive or polymerase chain reaction (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 Epstein-Barr virus (EBV) negative
•Medical History and Concurrent Diseases
•Subjects who have received 2 or more consecutive weeks of dialysis 1 month prior to enrollment OR anticipated to have prolonged dialysis post-transplantation
•Subjects with known intrinsic renal disease (e.g., a urine protein/ creatinine ratio > 150 mg/g or the presence of an abnormal number of red blood cells (RBCs) or granular casts in the urine) AND calculated GFR < 40 ml/min/1.73 m^2 body surface area (BSA) (abbreviated Modification of Diet in Renal Disease [MDRD]). Subjects must have a calculated GFR assessment within 1 month prior to enrollment.
•Subjects with known HIV
•Subjects with any prior or concurrent solid organ (e.g., heart, kidney, pancreas) or cell (e.g., islet, bone marrow) transplant or subjects deemed likely to have a second solid organ or cell transplant (e.g., islet, bone marrow) within the next 3 years.
•Subjects with a history of cancer within the last 5 years
•Allergies and Adverse Drug Reactions
•a) Hypersensitivity to any medications that will be used in the protocol
•Prohibited Treatments and/or Therapies
•Subjects receiving immunosuppressive agent(s) (e.g., methotrexate, abatacept, infliximab, etanercept, chemotherapy, etc.) within the past 6 months for other indications such as an autoimmune disease
•Subjects who received maintenance corticosteroids at a dose of > 5 mg/day of prednisone (or equivalent) for at least 7 consecutive days within the prior year for an underlying chronic inflammatory or autoimmune disease
•Subjects who have used any investigational drug within 30 days prior to the Day 1 visit
•Subjects previously treated with belatacept

排除标准

未提供

研究组 & 干预措施

Group 1: Basiliximab+Belatacept (MI) + MMF

Experimental

干预措施: Basiliximab (Drug)

Group 1: Basiliximab+Belatacept (MI) + MMF

Experimental

干预措施: Belatacept More Intensive (MI) (Drug)

Group 1: Basiliximab+Belatacept (MI) + MMF

Experimental

干预措施: Mycophenolate Mofetil (MMF) (Drug)

Group 2: Belatacept (MI) + MMF

Experimental

干预措施: Belatacept More Intensive (MI) (Drug)

Group 2: Belatacept (MI) + MMF

Experimental

干预措施: Mycophenolate Mofetil (MMF) (Drug)

Group 3: Belatacept Less Intensive (LI) + MMF

Experimental

干预措施: Belatacept Less Intensive (LI) (Drug)

Group 3: Belatacept Less Intensive (LI) + MMF

Experimental

干预措施: Mycophenolate Mofetil (MMF) (Drug)

Group 4: Tacrolimus + MMF

Other

干预措施: Tacrolimus (Drug)

Group 4: Tacrolimus + MMF

Other

干预措施: Mycophenolate Mofetil (MMF) (Drug)

Group 5: Tacrolimus

Active Comparator

干预措施: Tacrolimus (Drug)

结局指标

主要结局

Percentage of Participants Who Experienced at Least One Episode of Acute Rejection (AR), Graft Loss, or Death by 6 Months Post-transplant

时间窗: At 6 months posttransplant

Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading schema. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% (confidence interval) CI within each group, normal approximation is used if N\>=5, otherwise exact method is used.

Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)

时间窗: Day 1 (randomization) to Week 104 + within 56 Days after the last infusion/dose, Deaths were monitored up to database lock (20-June-2011)

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

Number of Participants Who Had AEs of Special Interest During the LTE

时间窗: Day 1 (randomization) through database lock (20-June-2011)

AE of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial).

Number of Participants With Marked Hematology Abnormalities During the LTE

时间窗: Every 4 weeks from Week 53 to Week 104.

Low platelet count: \<50\*10\^9 c/µl; Low leukocytes: \<2.0\*10\^3 c/µl; Low lymphocytes (absolute): \<0.5\*10\^3 c/µl; Low neutrophils (absolute): \<1.0\*10\^3 c/µl.

Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE

时间窗: Every 4 weeks from Week 53 to Week 104.

ULN= upper limit of normal; Normal ranges are provided by the Central Laboratory and may vary according to sex and age. High alanine aminotransferase (ALT): \>5.0\*ULN U/L; High aspartate aminotransferase (AST): \>5.0\*ULN U/L; High direct bilirubin: \>3.0\*ULN mg/dL; High g-glutamyl transferase (GGT): \>5.0\*ULN U/L; High total bilirubin: \>3.0\*ULN mg/dL; High creatinine: \> 3.0\*ULN mg/dL

Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE

时间窗: Every 4 weeks from Week 53 to Week 104.

Low Serum Potassium: \<3.0 meq/L; High serum potassium:\>6.0 mEq/L; Low serum magnesium:\<0.8 mEq/L; Low serum sodium: \<130 mEq/L; High serum sodium: \>155 mEq/L; Low inorganic phosphorus: \<2.0 mg/dL; High uric acid: \>10 mg/dL

次要结局

Percentage of Participants Surviving With Functional Graft: 12-month Treatment Phase(At 6 and 12 months)
Percentage of Participants Surviving With Functional Graft by End of Study (Includes LTE Data)(Day 1 (randomization) through database lock (20-June-2011))
Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by 12 Months(At 12 months posttransplant)
Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by End of Study (Includes LTE Data)(Day 1 (randomization) through database lock (20-June-2011))
Number of Participants Having Acute Rejections: 12-month Treatment Phase(3 , 6, and 12 months)
Number of Participants Having Acute Rejections During the LTE(Day 1 (randomization) through database lock (20-June-2011))
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months(3, 6 and 12 months posttransplant)
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE(Day 1 (randomization) through database lock (20-June-2011))
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months(3, 6 and 12 months posttransplant)
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months(3, 6 and 12 months posttransplant)
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE(Day 1 (randomization) through End of study (database lock of 20-June-2011))
Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months(3, 6, 9 and 12 months posttransplant)
Mean Change From Baseline in Measured Glomerular Filtration Rate (GFR): 12-month Treatment Phase(Baseline (2 month), 12 months posttransplant)
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase(Baseline [BL] (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplant)
Mean Change From Baseline in Calculated GFR During the LTE(Baseline (pretransplant time point), 1, 2, 3, 6,12, 18, 24, 30, 36 months posttransplant)
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12(Baseline (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplant)
Mean Change in Baseline Values of Cystatin C at 2 and 12 Months(Baseline (pretransplant), 2, and 12 months posttransplant)
Belatacept Pharmacokinetic (PK) Parameter: Maximum Serum Concentration(Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.)
Belatacept Pharmacokinetic (PK) Parameter: Time to Achieve the Maximum Plasma Concentration(Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.)
Belatacept PK Parameter: Area Under the Serum Concentration-time Curve to the End of the Dosing Period (AUCtau)(Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.)
Belatacept PK Parameter: Minimum Plasma Concentration(Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.)
Belatacept PK Parameter: Terminal Half-life(Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.)
Belatacept PK Parameter: Total Body Clearance(Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.)
Belatacept PK Parameter: Volume of Distribution(Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.)
Belatacept PK Parameter: Amount Excreted in Ascites Fluid Over Days 1 to 14(Days 1 to 14)
Belatacept PK Parameter: Clearance From Ascites Fluid(Days 1 to 14)
Belatacept Trough Concentration Before Each Infusion During the LTE(Samples were collected predose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105, 532, 728.)
Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) by 12 Months(6 and 12 months posttransplant)
Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) During the LTE(12 months posttransplant, end of study (database lock, 20-June-2011))
Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase(Baseline (pretransplant), 6 and 12 months (mo) posttransplant)
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE(BL (pretransplant), 12, 18, 24, 30 months (mo) posttransplant)
Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase(6 and 12 months posttransplant)
Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase(6 and 12 months posttransplant)
Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase(Baseline (pretransplant), 1, 6, 12 months posttransplant)
Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase(Baseline (pretransplant), 1, 6, 12 months posttransplant)
Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase(Baseline (pretransplant), 1, 6, 12 months posttransplant)
Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase(Baseline (pretransplant), 1, 6, 12 months posttransplant)
Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase(Baseline (pretransplant), 1, 6, 12 months posttransplant)
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase(Baseline (pretransplant), 1, 3, 6, 9, 12 months posttransplant)
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase(BL (pretransplant), 1, 3, 6, 9, 12 months posttransplant)
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase(BL (pretransplant), 1, 3, 6, 9, 12 months posttransplant)
Percentage of Participants Who Developed Hypertension in 12-month Treatment Phase(6 and 12 months posttransplant)
Percentage of Participants Who Have Hypertension at Any Given Time During the 12-month Treatment Phase(6 and 12 months posttransplant)
Number of Participants Who Received Anti-hypertensive Therapy at Month 12(12 months posttransplant)
Percentage of Participants With New Onset Diabetes Mellitus (NODM): 12-month Treatment Phase(6 and 12 months posttransplant)
Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase(6, 12 months (mth) posttransplant)
Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase(Day 1 (randomization) to 12 m + 8 week follow-up or ≤ 56 days after discontinuation of study medication)
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase(Day 1 (randomization) to 12 months or ≤ 56 days after discontinuation of study medication)
Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase(Baseline (pretransplant), 2, 4, 8, 12 weeks, and every 4 weeks for week 16 to 52)
Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase(Baseline (pretransplant), 4, 12, 24, 52 weeks)
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase(Baseline (pretransplant), Weeks 4, 12, 24, and 52)
Number of Participants Who Had Abnormalities in Electrocardiograms: 12-month Treatment Phase(Baseline (pretransplant), Week 52)
Change in Protein to Creatinine Ratio From Month 3 to Month 12.(Month 3 and 12)

研究者

发起方

Bristol-Myers Squibb

申办方类型

Industry

责任方

Sponsor

研究点 (20)

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