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

This study has been terminated.
(Sponsor decision to terminate the study)
Sponsor:
Information provided by:
Enzon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00415311
First received: December 20, 2006
Last updated: August 8, 2011
Last verified: August 2011
  Purpose

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


Condition Intervention Phase
Liver Transplantation
Drug: Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Enzon Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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 [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the pharmacokinetic (PK) profile of rhMBL [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Determine the pharmacodynamics (PD) (complement deposition) of rhMBL [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Determine the immunogenicity of rhMBL by testing for the presence of anti-rhMBL antibodies [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Detect preliminary evidence of activity of rhMBL by analyzing the incidence of infectious complications. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: December 2006
Study Completion Date: December 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00415311

Locations
United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, Nebraska
Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7400
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 372321
Sponsors and Collaborators
Enzon Pharmaceuticals, Inc.
Investigators
Principal Investigator: Alison Freifeld, MD University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198-5400
  More Information

No publications provided

Responsible Party: Nazish Huq, Clinical Project Manager, Enzon Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00415311     History of Changes
Other Study ID Numbers: EZN-2232-02
Study First Received: December 20, 2006
Last Updated: August 8, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Enzon Pharmaceuticals, Inc.:
Liver Transplantation
rhMBL

ClinicalTrials.gov processed this record on July 20, 2014