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.

• Conditions: The genotype 1 Chronic Hepatitis C Infection; MedDRA version: 9.1Level: HLTClassification code 10057212Term: Hepatitis viral infections

• Registration Number: EUCTR2007-005385-12-BG
• Lead Sponsor: GlobeImmune, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04-15
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. 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;
2. Two HCV RNA values of =1000 IU/mL within the screen period;
3. One of the following response criteria based on response to prior combination therapy with pegylated or non-pegylated interferon plus ribavirin:
• 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).
•Patients who are treatment naïve and have refused IFN therapy for reasons other than contraindication.
4. 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;
5. If female of childbearing potential, negative pregnancy test;
6. Age = 18 years;
7. Negative scratch test (immediate hypersensitivity, IgE mediated) to S. cerevisiae.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. 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;
2. History of significant non-HCV chronic liver disease, i.e. alcoholic hepatitis, autoimmune hepatitis;
3. Liver function:
•ALT or AST > 5 times the upper limit of normal (ULN).
•Alpha-fetoprotein level > 50 ng/mL (Alpha-fetoprotein level from ULN to 50 ng/mL must have a normal ultrasound during screening for inclusion).
•Total bilirubin > 1.8 mg/dL (except for elevations secondary to Gilbert syndrome).
•INR =1.4.
4. 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;
5. 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);
6. 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;
7. Subjects that required growth factors during their previous interferon/ribavirin treatment;
8. Subjects that received small molecule inhibitor therapy combined with an interferon based regimen. (subjects that received small molecule inhibitor monotherapy can be included);
9. Treatment for HCV infection within 28 days before screening;
10. Chronic hepatitis B infection or positive hepatitis B surface antigen (HBsAg) at screening;
11. Body weight >275 pounds;
12. History of other significant chronic diseases including:
•Poorly controlled diabetes
•clinically significant or symptomatic cardiovascular or cerebrovascular disease
•autoimmune disease
•autoimmune conditions associated with chronic HCV: Symptomatic cryoglobulinemia, Glomerulonephritis, Sjogren’s syndrome, Thyroid disease (subjects with stable thyroid disease may be eligible upon discussion with and approval of the medical monitor), Porphyria cutanea tarda
•active major psychiatric disease (includes history of major depression, psychosis, suicidal ideation or attempts, or in-patient hospitalization for psychiatric management).
•renal disease (serum creatinine >1.5 ULN).
•evidence of significant hematologic abnormalities: CD4+ cell count <200/uL,
Neutrophil count < 1.5 x 103/uL, WBC < 4000/uL, Platelets <150,000/uL, Hemoglobin <12.0 g/dL (males), <11g/dL (females)
13. Known history of HIV infection or positive HIV antibody test at screening;
14. History of cancer within the last 5 years with the exception of localized basal or squamous cell carcinoma or Stage 1A cervical cancer;
15. History of Crohn’s disease or ulcerative colitis;
16. History of major organ transplantation;
17. Concurrent and chronic therapy with immunosuppressive drugs including systemic corticosteroids. Short courses of steroids for exacerbation of normally well-controlled asthma or other conditions may be permitted after consultation with the Medical Monitor;
18. Concurrent therapy with herbal supplements taken specifically for the treatment of HCV is prohibited (i.e. milk thistle). Twenty eight day wash-out of HCV related herbals is required prior to Day 1;
1

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified