A Multicenter Study Evaluating the Safety and Tolerabilit... | NCT00415311

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

NCT00415311

Sponsor

Enzon Pharmaceuticals, Inc.

Status

Terminated

Last Update Posted

Aug 9, 2011Estimated

Enrollment

24Actual

Phase

Phase 1

Conditions

Liver Transplantation

Interventions

Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)
Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)
Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Status Module

Record Verification Date

Aug 2011

Overall Recruitment Status or Expanded Access Status

Terminated

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Sponsor decision to terminate the study

Expanded Access Info

Start Date

Dec 2006

Primary Completion Date

Jun 2009Actual

Completion Date

Dec 2009Actual

First Submitted Date

Dec 20, 2006

First Submission Date that Met QC Criteria

Dec 20, 2006

First Posted Date

Dec 22, 2006Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Aug 8, 2011

Last Update Posted Date

Aug 9, 2011Estimated

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

24Actual

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
0 mg/kg	Other	Drug: Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)
0.5 mg/kg	Other	Drug: Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)
1.0 mg/kg	Other	Drug: Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Intravenous Recombinant Human Mannose-Binding Lectin (rhMBL)	Drug	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

Outcomes Module

Primary Outcomes

Measure	Description	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 Outcomes

Measure	Description	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

Other Outcomes

Not provided

Eligibility Module

Eligibility 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.

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Alison Freifeld, MD	University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198-5400	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
University of California San Francisco		San Francisco	California	94143	United States
Nebraska Medical Center