Scale-up of Treatment of Hepatitis C Infection Among People Who Inject Drugs

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase IV, Open-label, Single Arm, Multicentre Trial of Grazoprevir/Elbasvir for Genotype 1 or 4 in People With Chronic Hepatitis C Virus Infection and Recent Injecting Drug Use or Receiving Opioid Substitution Therapy

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Grazoprevir/elbasvir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Grazoprevir/elbasvir<br>Grazoprevir/elbasvir (100mg/50mg) daily taken orally for 12 weeks. | Drug: Grazoprevir/elbasvir<br>* Grazoprevir/elbasvir (100mg/50mg) once daily for 12 weeks.<br>* Other names: Zepatier;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 12 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Completion | Number who completed HCV treatment as prescribed (12 weeks of grazoprevir/elbasvir (100mg/50mg) daily) | 12 weeks from treatment administration | 
| 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) | 12 weeks from treatment administration |