Belatacept in Liver Transplant Recipients

Bristol-Myers Squibb (BMS)

Status and phase: Terminated; Phase 2

Conditions: Immunosuppression in Solid Organ Transplant

Treatments: Drug: Belatacept Less Intensive (LI); Drug: Basiliximab; Drug: Belatacept More Intensive (MI); Drug: Mycophenolate Mofetil (MMF); Drug: Tacrolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT00555321

IM103-045

Details and patient eligibility

About

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

Enrollment: 260 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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260 participants in 5 patient groups

Group 1: Basiliximab+Belatacept (MI) + MMF

Experimental group

Treatment:

Drug: Basiliximab

Drug: Belatacept More Intensive (MI)

Drug: Mycophenolate Mofetil (MMF)

Group 2: Belatacept (MI) + MMF

Experimental group

Treatment:

Drug: Belatacept More Intensive (MI)

Drug: Mycophenolate Mofetil (MMF)

Group 3: Belatacept Less Intensive (LI) + MMF

Experimental group

Treatment:

Drug: Belatacept Less Intensive (LI)

Drug: Mycophenolate Mofetil (MMF)

Group 4: Tacrolimus + MMF

Other group

Description:

Other

Treatment:

Drug: Mycophenolate Mofetil (MMF)

Drug: Tacrolimus

Group 5: Tacrolimus

Active Comparator group

Treatment:

Drug: Tacrolimus