Belatacept in Liver Transplant Recipients
Information source: Bristol-Myers Squibb
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Immunosuppression in Solid Organ Transplant
Intervention: Tacrolimus (Drug); Basiliximab (Drug); Belatacept More Intensive (MI) (Drug); Belatacept Less Intensive (LI) (Drug); Mycophenolate Mofetil (MMF) (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: Bristol-Myers Squibb Official(s) and/or principal investigator(s): Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb
Summary
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
Clinical Details
Official title: Evaluation of Belatacept as First Line Immunosuppression in De Novo Liver Transplant Recipients
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Percentage of Participants Who Experienced at Least One Episode of Acute Rejection (AR), Graft Loss, or Death by 6 Months Post-transplantNumber of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data) Number of Participants Who Had AEs of Special Interest During the LTE Number of Participants With Marked Hematology Abnormalities During the LTE Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE
Secondary outcome: Percentage of Participants Surviving With Functional Graft: 12-month Treatment PhasePercentage of Participants Surviving With Functional Graft by End of Study (Includes LTE Data) Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by 12 Months Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by End of Study (Includes LTE Data) Number of Participants Having Acute Rejections: 12-month Treatment Phase Number of Participants Having Acute Rejections During the LTE Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months Mean Change From Baseline in Measured Glomerular Filtration Rate (GFR): 12-month Treatment Phase Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase Mean Change From Baseline in Calculated GFR During the LTE Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12 Mean Change in Baseline Values of Cystatin C at 2 and 12 Months Belatacept Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Belatacept Pharmacokinetic (PK) Parameter: Time to Achieve the Maximum Plasma Concentration Belatacept PK Parameter: Area Under the Serum Concentration-time Curve to the End of the Dosing Period (AUCtau) Belatacept PK Parameter: Minimum Plasma Concentration Belatacept PK Parameter: Terminal Half-life Belatacept PK Parameter: Total Body Clearance Belatacept PK Parameter: Volume of Distribution Belatacept PK Parameter: Amount Excreted in Ascites Fluid Over Days 1 to 14 Belatacept PK Parameter: Clearance From Ascites Fluid Belatacept Trough Concentration Before Each Infusion During the LTE Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) by 12 Months Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) During the LTE 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 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 Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase Percentage of Participants Who Developed Hypertension in 12-month Treatment Phase Percentage of Participants Who Have Hypertension at Any Given Time During the 12-month Treatment Phase Number of Participants Who Received Anti-hypertensive Therapy at Month 12 Percentage of Participants With New Onset Diabetes Mellitus (NODM): 12-month Treatment Phase Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase Number of Participants Who Had Abnormalities in Electrocardiograms: 12-month Treatment Phase Change in Protein to Creatinine Ratio From Month 3 to Month 12.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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
1. Subjects who have received 2 or more consecutive weeks of dialysis 1 month prior to
enrollment OR anticipated to have prolonged dialysis post-transplantation
2. 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.
3. Subjects with known HIV
4. 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.
5. 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
1. 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
2. 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
3. Subjects who have used any investigational drug within 30 days prior to the Day 1
visit
4. Subjects previously treated with belatacept
Locations and Contacts
Local Institution, Wien 1090, Austria
Local Institution, Rio De Janeiro 21041, Brazil
Local Institution, Clichy Cedex 92118, France
Local Institution, Lyon 69437, France
Local Institution, Montpellier 34295, France
Local Institution, Paris 75014, France
Local Institution, Toulouse Cedex 9 31059, France
Local Institution, Villejuif 94800, France
Local Institution, Berlin 13353, Germany
Local Institution, Hamburg 20246, Germany
Local Institution, Hannover 30625, Germany
Local Institution, Heidelberg 69120, Germany
Local Institution, Tuebingen 72076, Germany
Local Institution, Bergamo 24128, Italy
Local Institution, Padova 35128, Italy
Local Institution, Pisa 56124, Italy
Local Institution, Roma 00168, Italy
Local Institution, Barcelona 08036, Spain
Local Institution, Edmonton, Alberta T6G 2B7, Canada
Mayo Clinic Hospital, Phoenix, Arizona 85054, United States
Local Institution, Ciudad De Buenos Aires, Buenos Aires C1181ACH, Argentina
Usc University Hospital, Los Angeles, California 90033, United States
University Of California San Francisco Medical Center, San Francisco, California 94143, United States
Mayo Clinic Transplant Department, Jacksonville, Florida 32224, United States
Lifelink Healthcare Institute, Tampa, Florida 33606, United States
Emory University Hospital, Atlanta, Georgia 30322, United States
Northwestern University Feinberg School Of Medicine, Chicago, Illinois 60611, United States
Tulane Center For Abdominal Transplant, New Orleans, Louisiana 70112, United States
Henry Ford Hospital, Detriot, Michigan 48202, United States
University Of Minnesota, Minneapolis, Minnesota 55455, United States
Washington University School Of Medicine, St. Louis, Missouri 63110, United States
Nyu School Of Medicine, New York, New York 10016, United States
Westchester Medical Center, Valhalla, New York 10595, United States
Carolinas Medical Center, Charlotte, North Carolina 28203, United States
Univ. Of Cin. Coll. Of Med., Cincinnati, Ohio 45267, United States
Integris-Baptist Medical Ctr., Oklahoma City, Oklahoma 73112, United States
Local Institution, Toronto, Ontario M5G 2N2, Canada
Local Institution, Curitiba, Parana 80060, Brazil
Hospital Of The University Of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
Local Institution, Centro-Porto Alegre, Rio Grande Do Sul 90020, Brazil
Baylor University Medical Center, Dallas, Texas 75246, United States
Froedtert Memorial Lutheran Hospital, Milwaukee, Wisconsin 53226, United States
Additional Information
BMS Clinical Trials Disclosure For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
Starting date: January 2008
Last updated: September 17, 2012
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