Zepatier in Patients With Substance Use

Study Overview
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Brief Summary
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The goal of this study is to assess hepatitis C virus (HCV) treatment with Zepatier (elbasvir/grazoprevir) in HCV monoinfected and human immunodeficiency virus (HIV)-HCV co-infected, HCV treatment-naïve or peginterferon/ribavirin-experienced patients with HCV genotype 1a, without baseline NS5A resistance, 1b, or 4 and substance use in urban, multidisciplinary specialty clinics.

Detailed Description
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Previously, people who use substances and those without liver fibrosis or cirrhosis were excluded from receiving direct-acting antiviral (DAA) treatment due to Illinois Medicaid restrictions. These sobriety and staging restrictions were recently lifted. However, due to these previous stringent requirements for sobriety, many patients were not able to be treated for HCV. This created a data gap for real-world outcomes of HCV treatment in people who use substances. This study presents a unique opportunity to provide patients with hepatitis C treatment and obtain much needed data on the use of elbasvir/grazoprevir in patients with substance use and other underrepresented comorbidities. Additionally, this study will determine if our current standard of care for the treatment of HCV is effective for patients with substance use.

Official Title
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Cohort Study of Hepatitis C Virus Treatment With Zepatier (Elbasvir/Grazoprevir) in Genotype 1 or 4 HCV Treatment-Naïve or Peginterferon/Ribavirin-Experienced Patients With Substance Use in Urban, Multidisciplinary Specialty Clinics

Conditions
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Hepatitis C, Hiv, Coinfection, HIV, Substance Use Disorders

Intervention / Treatment
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* Drug: Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet [ZEPATIER]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (at least 18 years of age or older) Chronic HCV (HCV antibody positive with detectable HCV-RNA) HCV genotypes 1a, without the presence of baseline NS5A resistance (specifically, polymorphisms at amino acid positions 28, 30, 31, or 93), 1b, or 4 HCV treatment-naïve or peginterferon/ribavirin-experienced Managed by the UI Health Infectious Diseases Clinic or Liver Clinic Recent or current substance use (per self-report or electronic medical record (EMR) data within 90 days of the screening visit, with or without positive baseline urine toxicology), inclusive of one or more of the following: Opiate substitution therapy; Prescription medication misuse (including: opiates, sedatives, tranquilizers, hypnotics, and psychostimulants); Illicit substances; Injection drug use; Alcohol Exclusion Criteria: Incarcerated Pregnant or breastfeeding Decompensated liver disease (Child-Pugh B or C) Albumin below 3 g/dL Platelet count below 75,000 Unwilling to commit to treatment and/or monitoring Poor venous access inhibiting laboratory collection Any condition considered by the investigators to be a contraindication to study participation Hepatitis B virus (HBV) surface antigen (HBsAg) positive

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients living with HCV +/- HIV<br>HCV monoinfected and human immunodeficiency virus (HIV)-HCV co-infected, HCV treatment-naïve or peginterferon/ribavirin-experienced patients with HCV genotype 1a, without baseline NS5A resistance, 1b, or 4 and substance use treated with elbasvir/grazoprevir 50-100 mg fixed-dose-combination, 1 tablet by mouth daily, for 12 weeks. | Drug: Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet [ZEPATIER]<br>* Daily medication<br>* Other names: Zepatier;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR - PP | Proportion of patients in the per-protocol (PP) population with sustained virologic response (SVR). PP: excludes non-treatment related discontinuations and patients lost to follow-up before SVR-12 laboratory test. | 12 weeks after the end of therapy (SVR-12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR - stratified | PP SVR-12 stratified by pre-specified baseline characteristics: HCV monoinfection HIV-HCV co-infection Cirrhosis Positive baseline urine toxicology Men who have sex with men (MSM) Commercial sex work Diagnosed concomitant psychiatric disorder(s) Use of concomitant medication(s) Specific substance(s) used | 12 weeks after the end of therapy (SVR-12) | 
| Drug-Drug interactions (DDIs) | Interventions to prevent or remedy known or suspected DDIs between elbasvir/grazoprevir and concomitant prescription or over-the-counter medications, supplements, and substance of use | From enrollment to treatment completion or termination, which ever comes first, for up to 36 weeks | 
| Adherence | Self-reported adherence to elbasvir/grazoprevir, reported as number of missed doses and % missed doses of total doses | During 12 weeks of treatment | 
| SVR - ITT | Proportion of patients in the intention-to-treat (ITT) population with SVR-12. ITT: all patients who received at least one dose of Zepatier (elbasvir/grazoprevir) | 12 weeks after the end of therapy (SVR-12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, HIV-HCV coinfection, DAA, Elbasvir/grazoprevir