Liver Transplantation
Conditions
Keywords
Liver Transplantation, rhMBL
Brief summary
This is a multicenter, open-label, randomized, Phase 1B study evaluating liver transplant recipients receiving rhMBL (2 cohorts) or without rhMBL (1 cohort).
Detailed description
This is a multicenter, open-label, randomized, Phase 1B study evaluating liver transplant recipients receiving rhMBL (2 cohorts) or without rhMBL (1 cohort). Patients will have received an orthotopic liver transplant (OLT) or a living related donor (LRD) liver transplant. Patients in all cohorts are to receive immunosuppressant therapy and anti-infectious prophylactic supportive therapy according to institutional standards. The donor's mannose-binding lectin (MBL) genotype will be evaluated to determine the liver transplant recipient's study eligibility. For recipients receiving an OLT, a sample of liver tissue or lymph nodes will be collected from the donor liver at the time of organ harvest for MBL genotyping. For recipients receiving a LRD transplant, the MBL genotype of the LRD will be determined in a companion protocol, Screening Protocol to Evaluate Mannose-Binding Lectin (MBL) Genotype in Living Related Donors for Liver Transplant Recipients. A recipient whose donor has an A/O or O/O MBL genotype will be eligible to participate in this study. Patients will be randomized in a 2:2:1 ratio to receive up to 8 intravenous (i.v.) infusions of rhMBL at a dose of 0.5 or 1.0 mg/kg, or to receive no rhMBL, respectively. Approximately 20 patients will be treated in each of the 2 rhMBL arms, and approximately 10 patients will be treated with standard immunosuppressive agents and anti-infectious prophylaxis but not with rhMBL. Cohort 1 * Number of Patients 20 * rhMBL (mg/kg) 0.5 Cohort 2 * Number of Patients 20 * rhMBL (mg/kg) 1.0 Cohort 3 * Number of Patients 10 * rhMBL (mg/kg) None
Interventions
Intravenous(i.v.) administration for 8 weeks. Patients will be randomized to one of three cohorts: 0 mg/kg; 0.5 mg/kg, or 1.0 mg.kg
Sponsors
Enzon Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: Patients must meet all of the following criteria to be eligible for enrollment into the study: * Capable of understanding the protocol requirements and risks and providing written informed consent. * Scheduled to undergo OLT or LRD liver transplantation (single organ). Split grafts will not be allowed from OLT donors. * Donor has an MBL genotype of A/O or O/O. * Age ≥18 years old. * Willing to receive transfusions of blood products. Any patient who has given informed consent to participate in the clinical study and who meets all entry criteria for the study may participate in the genetic part of the study.
Exclusion criteria
Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the safety and tolerability of rhMBL administered i.v. at doses of 0.5 and 1.0 mg/kg, as 8 weekly doses over 8 weeks, in the setting of liver transplantation | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| Determine the pharmacokinetic (PK) profile of rhMBL | 3 months |
| Determine the pharmacodynamics (PD) (complement deposition) of rhMBL | 3 months |
| Determine the immunogenicity of rhMBL by testing for the presence of anti-rhMBL antibodies | 3 months |
| Detect preliminary evidence of activity of rhMBL by analyzing the incidence of infectious complications. | 3 months |
Countries
United States
Outcome results
None listed