Hepatitis C
Conditions
Keywords
Hepatitis C, HCV
Brief summary
The major goal of this project is to identify the role of the immune responses in the emergence of protease inhibitor mutants during therapy.
Detailed description
Objective 1: Evaluate the role of the immune responses in determining the emergence of HCV NS3 resistance mutation during protease inhibitor therapy Hypothesis 1 (HT 1): Low HLA binding to peptides containing protease inhibitor resistance mutations is associated with the emergence of protease inhibitor mutants during therapy and failure of the treatment. Hypothesis 2 (HT 2): A hole in T cell repertoire may allow emergence of protease inhibitor mutants during protease inhibitor therapy which leads to loss of the immune responses to these mutants and failure of treatment.
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
University of Cincinnati
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
All chronically HCV-infected patients who fail peg-IFN and RBV therapy and are eligible for combined treatment with PI therapy will be enrolled. Briefly, this includes: 1. Male or female 2. Age 18 to 65 3. Chronic HCV infection evidenced by liver biopsy or persistent HCV viremia for \>6 months 4. Treatment experienced and classified as non-responder or relapser to prior interferon-based therapy.
Exclusion criteria
1. Treatment naïve chronically HCV-infected patients. 2. Patients with a history of inflammatory bowel diseases (IBD) or suspected IBD, autoimmune diseases, including rheumatoid arthritis, and any patients on systemic immunomodulators. 3. Pregnancy 4. HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Completed Standard Treatment | 9 months | Blood samples will be drawn while the subject is on treatment to measure viral load and HCV-specific immune responses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Cleared the Virus | 9 months | Blood samples will be drawn while the subject is on treatment to measure viral load and HCV-specific immune responses |
Countries
United States
Participant flow
Recruitment details
We plan to enroll 10 chronically HCV-infected patients who fail the standard peg-IFN and Ribavirin (RBV) therapy (NR) and are therefore eligible for combined treatment with PI therapy according to the recent FDA approvals for Boceprevir. Patients will be recruited from the outpatient clinics at the University of Cincinnati College of Medicine
Participants by arm
| Arm | Count |
|---|---|
| 10 Hepatitis C Infected Subjects 10 chronically HCV-infected patients who fail the standard peg-IFN and Ribavirin therapy (NR) and are therefore eligible for combined treatment with Protease Inhibitor therapy. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | 10 Hepatitis C Infected Subjects |
|---|---|
| Age, Continuous Non responders | 60.00 years STANDARD_DEVIATION 5.29 |
| Age, Continuous Responders | 55.3 years STANDARD_DEVIATION 14.03 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 1 / 10 |
Outcome results
Primary
Number of Participants Who Completed Standard Treatment
Blood samples will be drawn while the subject is on treatment to measure viral load and HCV-specific immune responses.
Time frame: 9 months
Population: Measure HCV viral load and HCV-specific immune responses at baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 Hepatitis C Infected Subjects | Number of Participants Who Completed Standard Treatment | complete standard treatment | 10 participants |
| 10 Hepatitis C Infected Subjects | Number of Participants Who Completed Standard Treatment | not complete | 0 participants |
Secondary
Number of Participants Who Cleared the Virus
Blood samples will be drawn while the subject is on treatment to measure viral load and HCV-specific immune responses
Time frame: 9 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 Hepatitis C Infected Subjects | Number of Participants Who Cleared the Virus | responder | 7 participants |
| 10 Hepatitis C Infected Subjects | Number of Participants Who Cleared the Virus | Non-responder | 3 participants |