Clinical trial NCT00606086: Safety and Efficacy of the Therapeutic Vaccine GI-5005 Combined With Pegylated Interferon Plus Ribavirin Standard of Care Therapy Versus Standard of Care Alone in Patients With Genotype 1 Chronic Hepatitis C Infection
Official title: A Phase 2 Randomized, Open Label, Multi-center, Therapeutic Trial of the Efficacy, Immunogenicity, and Safety of GI-5005; an Inactivated Recombinant Saccharomyces Cerevisiae Expressing a Hepatitis C Virus NS3-Core Fusion Protein, Combined With Pegylated Interferon Plus Ribavirin Standard of Care Therapy Versus Standard of Care Alone, and GI-5005 Salvage of Standard of Care Failures, in Patients With Genotype 1 Chronic Hepatitis C Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Genotype 1 Chronic Hepatitis C
Keywords: Hepatitis, HCV, Liver disease, HepC
Lead sponsor: GlobeImmune
Sponsor class: INDUSTRY
First posted: 2008-02-01
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The GI-5005 therapeutic vaccine in combination with standard of care or standard of care alone will be injected under the skin of HCV subjects. Patients will be monitored for safety, immune responses and any therapeutic benefits related to the injections including EVR, ETR, and SVR.


Eligibility criteria: Inclusion Criteria:

* Chronic hepatitis C infection with genotype 1 based on serum positivity for HCV RNA or a positive test for serum anti-HCV antibody for at least 6 months;
* One of the following response criteria based on response to prior combination therapy with pegylated or non-pegylated interferon plus ribavirin:

Non-Responders

* Poor responders - a subset of non-responders who achieved \> 1 log10 but \< 2 log10 reduction in HCV RNA after a minimum of 12 weeks of prior interferon based therapy.
* Partial responders - a subset of non-responders who achieve at least a 2 log10 reduction in HCV RNA by 12 weeks, but do not achieve an end of treatment response (ETR defined as HCV RNA negativity by PCR assay at the end of a minimum of 6 months of therapy).

Naive

* Patients who are treatment naïve and have refused IFN therapy for reasons other than contraindication.
* Signed, written, informed consent from the patient or legal representative before any study-specific procedures are performed;
* Liver biopsy within 3 years of the screening visit, documenting extent of liver disease consistent with chronic hepatitis C with evidence of inflammation and/or fibrosis. Liver biopsy within 1 year for subjects consenting to paired biopsy testing. Eight unstained liver biopsy slides are required for the baseline sample and post-treatment sample for use in central blinded evaluation for paired biopsy testing;
* Age ≥ 18 years;
* Negative scratch test (immediate hypersensitivity, IgE mediated) to S. cerevisiae.

Exclusion Criteria:

* History of decompensated liver disease, including but not restricted to, portal hypertension as manifested by a known history of gastroesophageal varices, variceal bleeding, ascites or encephalopathy, histopathologic or clinical evidence of cirrhosis, hepatocellular carcinoma, or renal impairment consistent with hepatorenal syndrome;
* History of significant non-HCV chronic liver disease, i.e. alcoholic hepatitis, autoimmune hepatitis;
* Null response to prior IFN plus ribavirin therapy, defined as patients that have received at least 12 weeks of interferon-based treatment with \< 1 log10 reduction in viral load;
* Subjects treated with more than 1 complete hepatitis C regimen (subjects with a history of 1 complete prior regimen and a second incomplete prior regimen may be eligible upon discussion with and approval of the medical monitor);
* Subjects that required a dose reduction of \>25% of the planned exposure of IFN or \>50% of their planned ribavirin exposure during their previous interferon/ribavirin treatment;
* Subjects that required growth factors during their previous interferon/ribavirin treatment;
* Subjects that received small molecule inhibitor therapy combined with an interferon based regimen. (subjects that received small molecule inhibitor monotherapy can be included);
* Treatment for HCV infection within 28 days before screening;
* Chronic hepatitis B infection or positive hepatitis B surface antigen (HBsAg) at screening;
* Body weight \>275 pounds;
* Known history of HIV infection or positive HIV antibody test at screening;
* History of Crohn's disease or ulcerative colitis;
* Concurrent therapy with herbal supplements taken specifically for the treatment of HCV (i.e. milk thistle). Wash-out of HCV related herbals for 28 days prior to Day 1. Consult sponsor before excluding potential subjects;
* Alcohol and/or IV drug abuse within the past year;

Primary outcomes:
measure: EVR (Early Virologic Response)
timeFrame: At 12 weeks of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic Torrey Pines
state: California
city: San Diego
country: United States
facility: Research and Education inc.
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Englewood
country: United States
facility: South Denver Gastroenterology
state: Colorado
city: Farmingtom
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Marietta
country: United States
facility: NW Georgia Research Institute
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Medical Center
state: Hawaii
city: Valparaiso
country: United States
facility: Northwest Indiana Center for Clinical Research
state: Indiana
city: New Orleans
country: United States
facility: Tulane University Hospital
state: Louisiana
city: Laurel
country: United States
facility: Maryland Digestive Disease Research
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: Gastroenterology Associates, PA
state: Mississippi
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Newport News
country: United States
facility: Liver Institute of Virginia Bon Secours Health System
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
Study officials:
References: