A Phase IV Trial of Paritaprevir/Ritonavir, Ombitasvir, Dasabuvir for Chronic Hepatitis C Genotype 1 Virus Infection
- Conditions
- Hepatitis C, Chronic
- Interventions
- Drug: "3D" regimenDrug: "3D" regimen with ribavirin
- Registration Number
- NCT02498015
- Lead Sponsor
- Kirby Institute
- Brief Summary
A total of 100 people with chronic HCV and recent injection drug use or recipients of opioid substitution therapy will be enrolled in 5 countries and 21 study sites. Participants with genotype 1a infection or cirrhosis will receive 12 weeks of open-label paritaprevir/ritonavir/ombitasvir and dasabuvir ("3D"), and twice-daily ribavirin. Participants with genotype 1b infection without cirrhosis will receive 12 weeks of open-label "3D". The study consists of a screening phase (6 weeks), treatment phase (12 weeks) and follow-up phase (96 weeks) to evaluate treatment response and reinfection.
- Detailed Description
A total of 100 people with recent injection drug use or recipients of opioid substitution therapy will be enrolled from drug and alcohol clinics, tertiary liver and infectious diseases clinics and community health centres across Canada, Europe, New Zealand, France, and Australia. This will include at least 30 participants with F3/F4 liver disease. Participants will be considered recent injection drug users if they have used injection drugs in the 6 months prior to consent. Participants receiving stable opioid substitution therapy (stable dose for \>2 weeks) will also be included. Patients with frequent drug use that is judged by the treating physician to compromise treatment safety will be excluded. The study drugs consisting of two tablets of the co-formulated paritepravir/ritonavir/ombitasvir (75/50/12.5 mg) once daily, one dasabuvir tablet (250 mg) twice daily, ribavirin (1000 mg) daily in two divided doses (genotype 1a only and/or cirrhosis). Electronic blister packs will be used to improve and monitor treatment adherence. This innovative strategy with the "3D" interferon-free regimen could considerably enhance the capacity to scale-up HCV treatment among PWID, and is therefore being evaluated in this phase IV study within a well-defined PWID population.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 87
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description "3D" regimen "3D" regimen The "3D" regimen contain two tablets of co-formulated paritepravir/ritonavir/ombitasvir (75/50/12.5 mg) once daily, and one dasabuvir tablet (250 mg) twice daily for genotype 1b without cirrhosis. Treatment will be 12 weeks. "3D" regimen with ribavirin "3D" regimen with ribavirin The "3D" regimen with ribavirin contain two tablets of co-formulated paritepravir/ritonavir/ombitasvir (75/50/12.5 mg) once daily, one dasabuvir tablet (250 mg) twice daily, and ribavirin (1000 mg regardless of weight) daily in two divided doses for genotype 1a (with/without) and genotype 1b with cirrhosis. Treatment will be for 12 weeks.
- Primary Outcome Measures
Name Time Method The proportion of participants with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) 12 weeks post treatment To evaluate the proportion of participants with undetectable HCV RNA 12 weeks post end of treatment (SVR12) following the "3D" regimen with or without ribavirin for 12 weeks in people with chronic HCV genotype 1 infection.
- Secondary Outcome Measures
Name Time Method The proportion of participants with undetectable HCV RNA at 24 weeks post end of treatment (SVR24) 24 weeks post treatment To evaluate the proportion of participants with undetectable HCV RNA 24 weeks (SVR24) post end of treatment.
Change in injecting drug use and injecting risk behaviour Baseline to week 12 To evaluate the change in injecting drug use and injecting risk behaviours during and following treatment. Change in injecting drug use and injecting risk behaviour will be measured via a self report behavioural questionnaire completed by participants at baseline, week 4 during treatment, week 8 during treatment and end of treatment.
Change in health-related quality of life Questionnaire Baseline to week 12 To evaluate the change in health-related quality of life during treatment. Change in health-related quality of life will be measured by self report questionnaire (EQ-5D) at baseline, week 4 during treatment and end of treatment.
Treatment adherence Baseline to week 12 To evaluate the proportion of participants adherent to treatment (both on-treatment adherence and treatment discontinuation).
Impact of mixed HCV infection on treatment response Baseline to SVR12 To evaluate the rate of mixed HCV infection at baseline and among those with treatment non-response
The proportion of participants with undetectable HCV RNA at the end of treatment - week 12 End of treatment week 12 To evaluate the proportion of participants with undetectable HCV RNA at the end of treatment after receiving 12 weeks of "3D" regimen with or without ribavirin.
Change in mental health Baseline to week 12 To evaluate the change in mental health during treatment. Change in mental health will be measured by self report mental health questionnaire (Kessler10) at baseline, week 4 during treatment and end of treatment.
Change in opioid substitution therapy Baseline to week 12 To evaluate the change in OST during treatment (dose and any discontinuation)
Utility of HCV core antigen testing as a simple method for HCV monitoring Week 108 To evaluate the utility of HCV core antigen testing as a simple method for HCV monitoring including treatment response. HCV RNA will be measured using the HCV core antigen test and then compared to HCV RNA levels measured using standard methods (EDTA plasma samples and Roche TaqMan).
The proportion of participants with undetectable HCV RNA at 2 weeks following the initiation of treatment - week 2 2 weeks following the initiation of treatment To evaluate the proportion of participants with undetectable HCV RNA after receiving 2 weeks of "3D" regimen with or without ribavirin.
The proportion of participants with undetectable HCV RNA at 4 weeks following the initiation of treatment - week 4 4 weeks following the initiation of treatment To evaluate the proportion of participants with undetectable HCV RNA after receiving 4 weeks of "3D" regimen with or without ribavirin.
Association between adherence and response to treatment Early (0-3 weeks), mid (4-7 weeks), late (8-11 weeks) during treatment To evaluate the association between adherence and response to treatment \[including an evaluation of the impact of early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) missed doses on response to treatment\]; adherence will be measured via a self report questionnaire and pill count via return of the weekly blister packs. The impact of the number and timing of the missed pills will be evaluated.
Safety and tolerability (number and type of adverse events and serious adverse events) Baseline to week 24 (SVR24) To evaluate the number and type of adverse events and serious adverse
HCV reinfection rate Week 108 To evaluate the rate of HCV reinfection during and following treatment
Emergence of viral resistance-associated variants (RAVs) Baseline to week 12 To evaluate the emergence of viral resistance-associated variants (RAVs). HCV sequencing will be performed on the baseline EDTA plasma samples of all participants at baseline to detect any baseline RAVs and will be preformed on the EDTA plasma samples of the participants who experienced virological failure to detect the emergence of RAVs.
Trial Locations
- Locations (1)
The Kirby Institute, University of New South Wales Australia
🇦🇺Sydney, New South Wales, Australia