A Multicenter Study Evaluating the Safety and Tolerability of IV Recombinant Human Mannose Binding Lectin (rhMBL) in Liver Transplant Recipients. - Full Text View

Sponsored by:	Enzon Pharmaceuticals, Inc.
Information provided by:	Enzon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00415311

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 I Phase II

MedlinePlus related topics: Liver Transplantation

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety Study
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

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

Secondary Outcome Measures:

Determine the pharmacokinetic (PK) profile of rhMBL
determine the pharmacodynamics (PD) (complement deposition) of rhMBL
determine the immunogenicity of rhMBL by testing for the presence of anti-rhMBL antibodies
detect preliminary evidence of activity of rhMBL by analyzing the incidence of infectious complications.

Estimated Enrollment:	50
Study Start Date:	December 2006

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

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

Contacts

Contact: Joseph Kwiatek

908-541-8727

Locations

United States, Nebraska
Nebraska Medical Center	Recruiting
Omaha, Nebraska, United States, 68198-7400
Contact: Penny Hardiman 402-559-8930
Principal Investigator: Alison Freifeld, MD
United States, New York
Mount Sinai School of Medicine	Recruiting
New York, New York, United States, 10029
Contact: Nabil Rezk 212-659-8031 nabil.rezk@mountsinai.org
Contact: Rosemarie Gagliardi 212-659-8050 rosemarie.gagliardi@mountsinai.org
Principal Investigator: Sukru Emre, MD

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
Principal Investigator:	Sukru Emre, MD	Mount Sinai School of Medicine, New York, NY 10029

More Information

Study ID Numbers:	EZN-2232-02
Study First Received:	December 20, 2006
Last Updated:	August 1, 2007
ClinicalTrials.gov Identifier:	NCT00415311
Health Authority:	United States: Food and Drug Administration

Keywords provided by Enzon Pharmaceuticals, Inc.:

Liver Transplantation
rhMBL

ClinicalTrials.gov processed this record on January 16, 2009