First Liver Transplant Patients Receive Experimental Drug to Prevent Hepatitis C Infection

[Guest guest]

http://www.infectioncontroltoday.com/news/2011/01/first-liver-transplant-patient\

s-receive-experimental-drug-to-prevent-hepatitis-c-infection.aspx

First Liver Transplant Patients Receive Experimental Drug to Prevent Hepatitis C

Infection

Following a successful Phase 1 study for safety, researchers at MassBiologics of

the University of Massachusetts Medical School (UMMS) today announced the

beginning of a Phase 2 clinical trial testing the ability of a human monoclonal

antibody they developed to prevent hepatitis C virus (HCV) infection of a donor

liver in transplant patients.

The first patients were enrolled in the study in December. The primary goal of

this randomized, double-blind, placebo-controlled study is to test if the

monoclonal antibody, designated MBL-HCV1, prevents re-infection of patients

chronically infected with HCV who are undergoing liver transplantation.

MassBiologics plans to enroll 16 patients in the first part of the study. " We

are hopeful that positive results from this study will meet an important public

health need, and we could not take this important step without the willing and

thoughtful participation of these volunteers, " says Donna Ambrosino, MD,

executive director of MassBiologics and a professor of pediatrics at the Medical

School.

There are currently five hospitals participating in the trial—Massachusetts

General Hospital, Beth Israel Deaconess Medical Center, both in Boston, Lahey

Clinic in Burlington, Massachusetts, Yale-New Haven Hospital in Connecticut and

Mount Sinai Hospital in New York City—and others may join in the coming months.

The first six patients enrolled have come from three of these sites.

HCV damages the liver and is the leading indication for liver transplantation,

diagnosed in about half of the 6,000 patients who receive liver transplants each

year in the United States. According to the Centers for Disease Control and

Prevention (CDC), 3.2 million Americans are chronically infected with HCV and

approximately 10,000 die annually of the disease. Globally, as many as 170

million people are estimated to suffer from HCV infection.

For patients with end-stage liver disease from HCV infection, liver

transplantation is the only option. While it can be a life-saving treatment,

transplantation does not cure the disease. In nearly all cases, the patient's

new liver is eventually infected by HCV because the virus remains in the

patient's bloodstream during surgery. The course of recurrent HCV disease is

accelerated after transplantation and up to 20 percent of transplant patients

develop cirrhosis within five years. Unfortunately, the standard antiviral drugs

currently used to treat HCV prior to the onset of end-stage liver disease are

poorly tolerated after liver transplantation, leaving these patients with few

options.

To address this unmet medical need, the team at MassBiologics, working in

collaboration with investigators Gyongyi Szabo, MD, PhD, professor of medicine,

and Finberg, MD, professor and chair of the Department of Medicine at

UMMS, set out to develop a human monoclonal antibody that could clear HCV from a

patient's bloodstream and protect the donated liver from infection. In

pre-clinical studies, MBL-HCV1 successfully neutralized the virus in cell

culture and animal models of infection. A Phase 1 study in 31 healthy volunteers

completed in 2009 showed the antibody was well tolerated, with no serious side

effects. The Phase 1 study also measured the levels of the antibody in the

bloodstream and its ability to bind and inactivate the virus, thereby helping to

establish the dosage and protocol for the Phase 2 study now under way.

In the current study, patients will be randomized to receive an infusion of

either the antibody or placebo between one and four hours prior to surgery.

Then, during the phase of surgery when the diseased liver is removed, but before

the donor liver is implanted, patients will receive a second infusion of either

the antibody or placebo. After the surgery is completed, the patients will

receive a third infusion, and then daily infusions during the first week of

recovery. A final infusion is administered on the 14th day after liver

transplantation.

" The liver is the main reservoir for the hepatitis C virus, " says Brett Leav,

MD, senior director of clinical affairs at MassBiologics. " The virus circulates

in the blood, but only resides and replicates in the liver. So the idea here is

to clear the virus from the bloodstream before it has an opportunity to

re-infect the new liver. "

After transplantation, patients' blood will be tested on a regular basis to

screen for reemergence of HCV, which is usually detected within the first week

after transplantation. The primary goal of the Phase 2 trial is to see if the

patients who received the antibody are free of HCV at 42 days after

transplantation. An interim analysis is planned after the first 16 patients have

been enrolled in the trial, and a Data Safety and Monitoring Board overseeing

the study will assess the effectiveness and safety of MBL-HCV1.