Genotype 1 Chronic Hepatitis C
Conditions
Keywords
Hepatitis, HCV, Liver disease, HepC
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.
Interventions
DRUGGI-5005
40YU, subcutaneous
Pegylated interefron is an injection and ribavirin is an oral tablet
Sponsors
GlobeImmune
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EVR (Early Virologic Response) | At 12 weeks of treatment | Early Virologic Response (EVR) is a response measured by the reduction of virus in the blood after 12 weeks of treatment. |
Countries
United States
Participant flow
Recruitment details
38 Investigators in the U.S. (30 in U.S., 3 in Europe, 5 in India) were recruited to participate in this study. First subject was screened on November 12, 2007 and the last subject was screened on March 7, 2011.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Peg-IFN/Ribavirin Plus GI-5005 Subjects were given GI-5005 alone for 12 weeks (5 weekly followed by 2 monthly doses). After completion of GI-5005 monotherapy run in period peg-IFN/ribavirin (SOC) therapy was added to continued monthly administration of GI-5005 and the subjects were treated for subsequent 12 week period. At the end of this period, subjects who achieve an EVR continued to receive GI-5005 plus SOC therapy for an additional 36 weeks (naive subjects) or an additional 60 weeks (non-responder subjects). Subjects who did not achieve an EVR were followed for safety during a 36 week off treatment period. Any subject who discontinued SOC therapy due to intolerance at or prior to EVR assessment was treated with GI-5005 monotherapy for up to a total of 72 weeks. | 72 |
| Arm 2: Peg-IFN/Ribavirin or Peg-IFN/Ribavirin Plus GI-5005 Subjects were treated with 12 weeks of SOC (Peg-IFN plus Ribavirin) therapy. Subjects who achieve an EVR continued to receive SOC therapy for an additional 36 weeks (naive subjects) or an additional 60 weeks (non-responder subjects). Subjects who did not achieve an EVR, GI-5005 was added to SOC therapy and study drug administration continued for up to an additional 62 weeks. Subjects who discontinued SOC therapy due to intolerance were treated with GI-5005 monotherapy for up to 72 weeks. | 68 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 4 | 8 |
| Overall Study | Non-compliance | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Randomized, not treated | 1 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Arm 2: Peg-IFN/Ribavirin or Peg-IFN/Ribavirin Plus GI-5005 | Total | Arm 1: Peg-IFN/Ribavirin Plus GI-5005 |
|---|---|---|---|
| Age, Continuous | 49 years | 48 years | 48 years |
| Region of Enrollment Europe | 4 participants | 10 participants | 6 participants |
| Region of Enrollment India | 2 participants | 6 participants | 4 participants |
| Region of Enrollment United States | 62 participants | 124 participants | 62 participants |
| Sex: Female, Male Female | 23 Participants | 53 Participants | 30 Participants |
| Sex: Female, Male Male | 45 Participants | 87 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 71 | 65 / 65 |
| serious Total, serious adverse events | 14 / 71 | 7 / 65 |
Outcome results
Primary
EVR (Early Virologic Response)
Early Virologic Response (EVR) is a response measured by the reduction of virus in the blood after 12 weeks of treatment.
Time frame: At 12 weeks of treatment
Population: One hundred forty subjects were randomized, only 133 subjects received at least one dose of study drug. Subjects who did not receive at least one dose of study drug were removed from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Peg-IFN/Ribavirin Plus GI-5005 | EVR (Early Virologic Response) | 79.4 percentage of participants |
| Arm 2: Peg-IFN/Ribavirin or Peg-IFN/Ribavirin Plus GI-5005 | EVR (Early Virologic Response) | 78.5 percentage of participants |
p-value: 1Cochran-Mantel-Haenszel test