Hepatitis C
Conditions
Keywords
Hepatitis C virus, People who inject drugs, Drug users, Direct acting antiviral (DAA), Infectious diseases, Prisoners
Brief summary
The purpose of the study is to assess how feasible it is to treat and prevent the transmission of Hepatitis C in the prison setting to achieve substantial reductions in the incidence and prevalence of Hepatitis C. It is hypothesised that a rapid scale-up of Hepatitis C Virus (HCV) treatment with interferon-free Direct Acting Anti-virals (DAAs) in prison inmates will achieve a \>50% reduction in the incidence of HCV infection over a two year period in the prison setting.
Detailed description
The study will be conducted initially in two maximum security prisons located in New South Wales, Australia and comprises four phases: Phase 1, Surveillance of HCV Incidence and Prevalence and Liver Disease Burden: The HCV incidence and prevalence phase is a prospective longitudinal cohort. HCV incidence and prevalence and liver disease burden will be monitored through regular six-monthly cross-sectional surveys of participants for 3.5 years. Phase 2, Modelling: The data from year 1 of the surveillance of HCV incidence and prevalence phase will be used to model the number of participants required to be treated to demonstrate a 50% reduction in incidence. Phase 3, Treatment Intervention: The treatment intervention will only be conducted in one of the maximum security prisons (Treatment Prison). The second prison will continue to care for HCV infected inmates as per standard of care (Control Prison). The intervention component of this study will consist of a phase IV open-label study of interferon-free DAAs for the treatment of HCV infection. The treatment phase will commence in year 2 and will be two years in duration. The exact drug combination and regimen to be used in the treatment intervention will be determined in year 1 once phase II and III data of sofosbuvir and ledipasvir and other potential interferon-free DAA regimens are published. The exact number of participants required to demonstrate a 50% reduction in incidence will be determined during the modelling phase. Phase 4, Cost-effectiveness: During the treatment intervention phase participants will be required to complete a survey to obtain estimates of health outcomes (EQ-5D survey) at regular intervals. This data will be used by the health economist to determine the cost effectiveness of treatment as prevention in the prison setting.
Interventions
The treatment phase will commence in year 2. This is 12 weeks of the pangenotypic sofosbuvir/velpatasvir 400/100mg, coformulated into one tablet daily.
Sponsors
Kirby Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Surveillance of HCV Incidence and Prevalence Inclusion criteria 1. 18 years of age or older 2. Voluntarily signed the (surveillance phase) informed consent form. 3. Adequate English and mental health status to provide written informed consent and comply with study procedures
Exclusion criteria
1\) Prisoners of a security classification which makes clinic attendance for study visits logistically difficult 5.2 Treatment Intervention Inclusion criteria 1. 18 years of age or older. 2. Voluntarily signed the (treatment phase) informed consent form. 3. Detectable HCV RNA in plasma. 4. HCV genotypes 1-6 5. Anticipated incarceration duration \>12 weeks following the planned commencement of therapy. 6. Compensated liver disease where the following criteria must be met: 1. INR\< 1.8 2. Albumin \>30 g/L 3. Bilirubin \<35umol/L 7. Prisoners with Fibroscan \> 12KPa or AFP \>50 ng/mL must have an abdominal ultrasound or CT scan without evidence of hepatocellular carcinoma within 2 months prior to screening. 8. Negative pregnancy test at baseline (females of childbearing potential only). 9. \[For prisoners released during treatment or follow-up\] If engaging in sexual intercourse which may potentially result in pregnancy, all fertile males must be using effective contraception during treatment and during the 90 days after treatment end, and all fertile females must be using effective contraception during treatment and during the 30 days after treatment end 10. If co-infection with HIV is documented, the subject must meet the following criteria: 1. Antiretroviral (ARV) untreated for \>8 weeks preceding screening visit with CD4 T cell count \>500 cells/mm3 OR 2. On a stable ARV regimen for \>8 weeks prior to screening visit, with CD4 T cell count \>200 cells/mm3 and an undetectable plasma HIV RNA level. * Suitable ARV include: * Nucleos(t)ide reverse transcriptase inhibitors: Tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), emtricitabine (FTC)Non-nucleoside reverse transcriptase inhibitors: Rilpivirine * Protease inhibitors: Atazanavir, darunavir, lopinavir, ritonavir * Integrase inhibitors: Dolutegravir, raltegravir, elvitegravir/cobicistat * Contraindicated ARV include: * Efavirenz (50% reduction in velpatasvir exposure) * Didanosine * Zidovudine * Tipranavir Other ARV agents may be permissible at the time of study commencement pending further drug-drug interaction studies; please discuss with the Medical Monitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatitis C virus (HCV) incidence | 2 years | Incidence of HCV infection over a two year period in a network of four participating correctional centres. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SVR12 | 24 weeks | The proportion of patients with undetectable HCV RNA at 12 weeks following the end of treatment (SVR12) |
| ETR | 12 weeks | The proportion of patients with an end of treatment response (ETR) |
| Rapid Virological Response (RVR) | 4 weeks | The proportion of patients with undetectable HCV RNA at 4 weeks following the initiation of treatment (RVR) |
| Treatment adherence | 12 weeks | The proportion adherent to therapy (both on-treatment adherence and treatment discontinuation) and the association between adherence and response to treatment |
| Hepatitis C virus prevalence | 2 years | Change in prevalence of HCV infection over a two year period in a network of four participating correctional centres. |
| Treatment uptake | 2 years | The rate of HCV treatment uptake among eligible inmates and reasons for non-uptake |
| On-treatment change in illicit drug use | 24 weeks | Changes in illicit drug use behaviours during treatment |
| HCV reinfection rate | 2 years | The rate of HCV reinfection following treatment |
| Number of patients with adverse events | 16 weeks | Safety and tolerability of the treatment regimen |
Countries
Australia
Outcome results
None listed