A Multicenter Study Evaluating the Safety and Tolerability of Intravenous rhMBL in Liver Transplant Recipients.

A Multicenter, Open-Label, Randomized, Phase 1B Study Evaluating the Safety and Tolerability of Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL) in Liver Transplant Recipients

This is a multicenter, open-label, randomized, Phase 1B study evaluating liver transplant recipients receiving rhMBL (2 cohorts) or without rhMBL (1 cohort).

Study Overview

• Status: Terminated
• Conditions: Liver Transplantation
• Intervention / Treatment: Drug: Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7400
      • Nebraska Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 372321
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 exclusion criteria will not be eligible for enrollment.

• Concurrent serious medical illness, in the judgment of the principal investigator (PI), which could potentially interfere with protocol compliance.
• Positive screening pregnancy test or is breast-feeding.
• Female or male patient of reproductive capacity unwilling to use methods appropriate to prevent pregnancy during this study.
• Any condition that, in the opinion of the PI or Enzon makes the patient unsuitable for the study.
• Current participation in another clinical study with an investigational agent and/or use of an investigational drug (not including investigational use of an approved drug) in the 30 days before the first dose of rhMBL.
• Prior liver transplants.
• Systemic chemotherapy within 1 year before liver transplantation.
• Serum creatinine >5 mg/dL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 0.5 mg/kg	Drug: Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL); 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
Other: 1.0 mg/kg	Drug: Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL); 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
Other: 0 mg/kg	Drug: Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL); 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Enzon Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Alison Freifeld, MD, University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198-5400

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: December 20, 2006
• First Submitted That Met QC Criteria: December 20, 2006
• First Posted (Estimate): December 22, 2006

Study Record Updates

• Last Update Posted (Estimate): August 9, 2011
• Last Update Submitted That Met QC Criteria: August 8, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Liver Transplantation; rhMBL
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Coagulants; Agglutinins; Lectins
• Other Study ID Numbers: EZN-2232-02