Hepatitis C
Conditions
Brief summary
This study is a phase IV, open-label, single arm, multicentre study whose aim is to assess whether interferon-free and ribavirin-free Direct Acting Antiviral (DAA) Hepatitis C Virus (HCV) therapy with grazoprevir/elbasvir, will be feasible for the treatment of People who inject drugs (PWID) with recent injecting drug use or people receiving opioid substitution therapy and chronic HCV genotype 1 or 4 infection.
Detailed description
A prospective, observational cohort design will be used to enrol patients attending tertiary, drug and alcohol and primary health care services in Sydney, Australia. The study consists of a treatment phase (12 weeks) and a follow-up phase (up to 3 years) where participants will be followed every 3 months for the first year and every 6 months in years 2-3 to evaluate treatment response and reinfection. The effectiveness of the treatment will be assessed by looking at the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following therapy with grazoprevir/elbasvir and evaluate demographic and clinical predictors of non-response.
Interventions
Grazoprevir/elbasvir (100mg/50mg) once daily for 12 weeks.
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
No
Inclusion criteria
* Participants have voluntarily signed the informed consent form. * Be ≥18 years of age on day of signing informed consent form. * Have chronic HCV genotype 1 or 4 infection (defined as detectable HCV RNA). * Recent injecting drug use (previous 6 months) or receiving opioid substitution therapy. * HIV-1 infected subjects enrolled in the study must meet the following criteria: * Have HIV infection documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry (Baseline) and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load * b) Be on HIV Antiretroviral Therapy (ART) for at least 4 weeks prior to study entry using an ART regimen that is allowable with the intended DAA regimen as determined by the current PI and the Liverpool drug interaction website (http://www.hiv-druginteractions.org/) or current prescribing guidelines for elbasvir/grazoprevir OR be naive to treatment with any antiretroviral therapy (ART) with a baseline CD4 count of \>200 and have no plans to initiate ART treatment while participating in this study and through to at least Follow-up Week 4. * Negative pregnancy test at screening and baseline (females of childbearing potential only). * All fertile males and females must be using effective contraception during treatment and during 14 days after treatment end.
Exclusion criteria
* Is taking or plans to take any prohibited medications as per DAA Product Information or herbal supplements, including but not limited to St. John's Wort (Hypericum perforatum) within 2 weeks of Baseline. * Is currently using or intends to use barbiturates. * Is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from Baseline and continue throughout treatment, and after the last dose of study medication (as per the regimen requirements), or longer if dictated by local regulations. * Has any condition or pre-study laboratory abnormality, ECG abnormality or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the subject. * Had a life-threatening SAE during the screening period. * Has exclusionary laboratory values as listed below: * Haemoglobin \< 9.5 g/dL for both males and females * Platelets \< 50 x 10\^3 /µL * Serum albumin \< 3.0 g/dL * Patients with Child Pugh-B or C decompensated cirrhosis * Previous HCV treatment-experience. * Ongoing severe psychiatric disease as judged by the treating physician. * Frequent injecting drug use that is judged by the treating physician to compromise treatment safety. * Inability or unwillingness to provide informed consent or abide by the requirements of the study. * Is Hepatitis B surface antigen (HBsAg) positive NOTE: Sanger sequencing will be performed on a pre-treatment sample on all participants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12) | 12 weeks post treatment | Number with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following 12 weeks of daily grazoprevir/elbasvir (100mg/50mg) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Completion | 12 weeks from treatment administration | Number who completed HCV treatment as prescribed (12 weeks of grazoprevir/elbasvir (100mg/50mg) daily) |
| End of Treatment Response (Negative HCV RNA at the End of Treatment) | 12 weeks from treatment administration | Number with undetectable HCV RNA at end of treatment following 12 weeks of daily Grazoprevir/Elbasvir (100mg/50mg) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and Specificity of the Finger-stick Xpert® HCV Viral Load Assay for HCV RNA Detection | 12 week post treatment | To determine the sensitivity and specificity of the Xpert® HCV Viral Load assay for HCV RNA detection in samples collected by finger-stick capillary whole-blood. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Grazoprevir/Elbasvir Grazoprevir/elbasvir (100mg/50mg) daily taken orally for 12 weeks. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Incarceration | 1 |
| Overall Study | Lost to Follow-up | 5 |
Baseline characteristics
| Characteristic | Grazoprevir/Elbasvir |
|---|---|
| Age, Customized ≤46 years | 16 Participants |
| Age, Customized >46 years | 16 Participants |
| Any alcohol use in the previous month | 24 Participants |
| Any injecting drug use in the previous month | 29 Participants |
| Any non-injecting drug use in the previous month | 11 Participants |
| Current opioid substitution therapy (OST) | 18 Participants |
| Hazardous alcohol use in the previous month | 23 Participants |
| Hepatitis C virus (HCV) genotype 1a | 29 Participants |
| Hepatitis C virus (HCV) genotype 1b | 3 Participants |
| History of opioid substitution therapy (OST) | 23 Participants |
| Income Disability/social services | 30 Participants |
| Income Full time employment | 0 Participants |
| Income Other | 1 Participants |
| Income Part time employment | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Caucasian | 22 Participants |
| Race/Ethnicity, Customized Ethnicity Non-caucasian | 10 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 22 Participants |
| Stage of liver disease Cirrhosis (F4) | 2 Participants |
| Stage of liver disease Moderate or advanced fibrosis (F2-F3) | 7 Participants |
| Stage of liver disease No or mild fibrosis (F0-F1) | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 5 / 32 |
Outcome results
Primary
Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12)
Number with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following 12 weeks of daily grazoprevir/elbasvir (100mg/50mg)
Time frame: 12 weeks post treatment
Population: All enrolled
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grazoprevir/Elbasvir | Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12) | SVR12 | 24 Participants |
| Grazoprevir/Elbasvir | Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12) | No test performed | 2 Participants |
| Grazoprevir/Elbasvir | Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12) | Lost to follow-up | 5 Participants |
| Grazoprevir/Elbasvir | Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12) | Incarcerated | 1 Participants |
Secondary
End of Treatment Response (Negative HCV RNA at the End of Treatment)
Number with undetectable HCV RNA at end of treatment following 12 weeks of daily Grazoprevir/Elbasvir (100mg/50mg)
Time frame: 12 weeks from treatment administration
Population: Those who completed treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grazoprevir/Elbasvir | End of Treatment Response (Negative HCV RNA at the End of Treatment) | ETR | 24 Participants |
| Grazoprevir/Elbasvir | End of Treatment Response (Negative HCV RNA at the End of Treatment) | Not tested | 2 Participants |
Secondary
Number of Participants With Treatment Completion
Number who completed HCV treatment as prescribed (12 weeks of grazoprevir/elbasvir (100mg/50mg) daily)
Time frame: 12 weeks from treatment administration
Population: All enrolled
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grazoprevir/Elbasvir | Number of Participants With Treatment Completion | Treatment completion | 26 Participants |
| Grazoprevir/Elbasvir | Number of Participants With Treatment Completion | Lost to follow-up | 5 Participants |
| Grazoprevir/Elbasvir | Number of Participants With Treatment Completion | Incarcerated | 1 Participants |
Other Pre-specified
Sensitivity and Specificity of the Finger-stick Xpert® HCV Viral Load Assay for HCV RNA Detection
To determine the sensitivity and specificity of the Xpert® HCV Viral Load assay for HCV RNA detection in samples collected by finger-stick capillary whole-blood.
Time frame: 12 week post treatment
Population: Only 22 had both Xpert and plasma samples collected. Some participants had \>1 paired sample. HCV RNA from plasma was compared to the Xpert result. Sensitivity is number of positive Xpert results divided by the number of positive plasma results. The specificity is number of negative Xpert results divided by the number of negative plasma results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Grazoprevir/Elbasvir | Sensitivity and Specificity of the Finger-stick Xpert® HCV Viral Load Assay for HCV RNA Detection | Specificity | 95.7 Percentage |
| Grazoprevir/Elbasvir | Sensitivity and Specificity of the Finger-stick Xpert® HCV Viral Load Assay for HCV RNA Detection | Sensitivity | 100 Percentage |