Hepatitis C, Chronic
Conditions
Keywords
hepatitis C, treatment, injection drug users or receiving opiate substitution therapy
Brief summary
This sudy will determine whether shortening treatment for hepatitis C is feasible, safe and effective for patients who are current injection drug users or receiving opiate substitution therapy and who are responding well to treatment early on.
Detailed description
The study will evaluate the feasibility, safety and effectiveness of shortened treatment for hepatitis C genotypes 2/3 in current injection drug users or receiving opiate substitution therapy. Treatment will be with pegylated interferon alfa 2b (directly observed) and ribavirin for 12 weeks in those that have non-quantifiable (\<15 IU/ml detected and \<15 IU/ml undetected) HCV RNA or undetectable HCV RNA on qualitative assay at week 4 and 24 weeks in those that have quantifiable (≥15 IU/ml) HCV RNA or detectable HCV RNA on qualitative assay at week 4.
Interventions
DRUGPegylated interferon alfa 2b
Pegylated interferon alfa 2b 1.5 mcg/kg/week to a maximum of 150 mcg/week administered subcutaneously once weekly directly observed.
DRUGRibavirin
Ribavirin - 800-1400 mg daily according to weight taken orally with food, self administered in split doses.
Sponsors
Merck Sharp & Dohme LLC
Kirby Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age * chronic HCV infection * HCV genotype 2/3 infection * active injection drug use (within 24 weeks prior to consent) or currently receiving opiate substitution therapy * compensated liver disease * negative pregnancy test (within 24 hours of first dose of study medication) * effective contraception for the duration of the study * written informed consent
Exclusion criteria
* previous interferon or ribavirin therapy * investigation drug use in the 6 weeks prior to first dose of study medication * infection with HCV genotypes other than 2/3 * HIV infection * HBV infection * ongoing severe psychiatric disease * frequent drug use that is judged by the treating physician to compromise treatment safety * standard clinical and medical exclusions for treatment with pegylated interferon alfa 2b and ribavirin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Efficacy | 36 weeks | The primary outcome measure is the number of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following directly observed PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non-quantifiable (\<15 IU/ml detected and \<15 IU/ml undetected) HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy and for 24 weeks in participants with quantifiable (≥15 IU/ml) HCV RNA or detectable HCV RNA on qualitative assay at week 4 of therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Adherence | 48 weeks | Evaluate the adherence (\>80 of PEG-IFN, \>80% of RBV, \>80% of time) to directly observed PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non-quantifiable HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy and for 24 weeks in participants with quantifiable HCV RNA or detectable HCV RNA on qualitative assay at week 4 of therapy. |
| Treatment Response (ETR & SVR24) | 48 weeks | Evaluate the percentage with undetectable HCV RNA at end of treatment (ETR) and 24 weeks post end of treatment (SVR24) in participants treated with PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non quantifiable HCV RNA or undetectable HCV RNA at week 4 of therapy and for 24 weeks in participants with quantifiable HCV RNA or detectable HCV RNA at week 4 of therapy. |
| Behavioral and Quality of Life | 48 weeks | Evaluate changes in illicit drug use, opiate substitution therapy, depression, suicidal ideations and health-related quality of life in participants treated with PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non-quantifiable HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy and for 24 weeks in participants with quantifiable HCV RNA or detectable HCV RNA at week 4 of therapy. |
Countries
Australia, Belgium, Canada, Germany, Norway, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Treatment Duration (24 Weeks) Subjects with detectable HCV RNA after four weeks of therapy will continue on PEG-IFN and ribavirin until week 24 and follow-up for an additional 24 weeks following treatment completion (48 weeks in total).
Pegylated interferon alfa 2b: Pegylated interferon alfa 2b 1.5 mcg/kg/week to a maximum of 150 mcg/week administered subcutaneously once weekly directly observed.
Ribavirin: Ribavirin - 800-1400 mg daily according to weight taken orally with food, self administered in split doses. | 26 |
| Shortened Treatment Duration (12 Weeks) Subjects with undetectable HCV RNA after four weeks of therapy will continue on PEG-IFN and ribavirin until week 12 and follow-up for an additional 24 weeks following treatment completion (36 weeks in total).
Pegylated interferon alfa 2b: Pegylated interferon alfa 2b 1.5 mcg/kg/week to a maximum of 150 mcg/week administered subcutaneously once weekly directly observed.
Ribavirin: Ribavirin - 800-1400 mg daily according to weight taken orally with food, self administered in split doses. | 61 |
| Discontinued Prior to RVR Participants who discontinued therapy prior to RVR assessment at week 4 and were therefore not placed in either study arms. | 6 |
| Total | 93 |
Baseline characteristics
| Characteristic | Standard Treatment Duration (24 Weeks) | Shortened Treatment Duration (12 Weeks) | Discontinued Prior to RVR | Total |
|---|---|---|---|---|
| Age, Continuous | 40 years | 41 years | 50 years | 41 years |
| Sex: Female, Male Female | 3 Participants | 12 Participants | 1 Participants | 16 Participants |
| Sex: Female, Male Male | 23 Participants | 49 Participants | 5 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 26 | 60 / 61 | 5 / 6 |
| serious Total, serious adverse events | 4 / 26 | 6 / 61 | 1 / 6 |
Outcome results
Primary
Treatment Efficacy
The primary outcome measure is the number of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following directly observed PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non-quantifiable (\<15 IU/ml detected and \<15 IU/ml undetected) HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy and for 24 weeks in participants with quantifiable (≥15 IU/ml) HCV RNA or detectable HCV RNA on qualitative assay at week 4 of therapy.
Time frame: 36 weeks
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Treatment Duration (24 Weeks) | Treatment Efficacy | 10 Participants |
| Shortened Treatment Duration (12 Weeks) | Treatment Efficacy | 51 Participants |
| Discontinued Prior to RVR | Treatment Efficacy | 0 Participants |
Secondary
Behavioral and Quality of Life
Evaluate changes in illicit drug use, opiate substitution therapy, depression, suicidal ideations and health-related quality of life in participants treated with PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non-quantifiable HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy and for 24 weeks in participants with quantifiable HCV RNA or detectable HCV RNA at week 4 of therapy.
Time frame: 48 weeks
Secondary
Treatment Adherence
Evaluate the adherence (\>80 of PEG-IFN, \>80% of RBV, \>80% of time) to directly observed PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non-quantifiable HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy and for 24 weeks in participants with quantifiable HCV RNA or detectable HCV RNA on qualitative assay at week 4 of therapy.
Time frame: 48 weeks
Secondary
Treatment Response (ETR & SVR24)
Evaluate the percentage with undetectable HCV RNA at end of treatment (ETR) and 24 weeks post end of treatment (SVR24) in participants treated with PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non quantifiable HCV RNA or undetectable HCV RNA at week 4 of therapy and for 24 weeks in participants with quantifiable HCV RNA or detectable HCV RNA at week 4 of therapy.
Time frame: 48 weeks