A Pilot Study of Treating HCV at a Psychiatrist-staffed Outpatient Addiction Clinic

Study Overview
=================
Brief Summary
-----------------
The main purpose of this pilot study is to investigate the safety, effectiveness and tolerability of the study medication in the treatment of people with chronic hepatitis C virus infection who regularly attend a psychiatrist-staffed clinic for opiate addiction treatment.

Detailed Description
-----------------
An estimated 3.2 million people in the United States are currently infected with hepatitis C virus (HCV). Since 1990, when the US introduced screening of the blood supply for HCV, injection drug use has been the primary mode of HCV transmission in the United States. It is widely recognized that addressing the HCV epidemic among people who inject drugs (PWID) depends on increasing access to: 1) clean injection equipment; 2) opiate substitution therapy (OST); 3) curative HCV treatment; and 4) assistance with comorbid psychiatric conditions and social issues (Robaeys, C et al, 2013). Nevertheless, access to HCV treatment among current and former injection drug users is thought to be limited by several factors including: 1) insufficient number of infectious disease and gastroenterology providers and 2) provider and third-party payor concerns about adherence to medication and the risk of reinfection (Aspinall, EJ et al, 2013). Strategies to increase access among current and former injection drug users to direct acting antiviral drugs are urgently needed. The purpose of the current study is to assess the impact of co-treating chronic hepatitis C infection and opiate dependence within the context of an outpatient addiction clinic staffed by psychiatrists. The beneficial impact of co-treating opiate dependence and an infectious illness has been demonstrated in the case of HIV infection. Altice and colleagues conducted an observational study of HIV-infected opiate-dependent patients who were offered OST with buprenorphine/naloxone at 10 different HIV clinics. Subjects initiating buprenorphine/naloxone were more likely to initiate or remain on ART (antiretroviral therapy) (Altice, 2011). The Extension for Community Healthcare Outcomes (ECHO) program has demonstrated that with proper training and mentorship, primary care providers with no prior experience in managing HCV are able to treat the disease effectively (Arora et al, 2011). Since the publication of the ECHO study, the treatment of HCV has become considerably less complicated due to the widespread availability of safe, highly effective single tablet regimens, such as Epclusa. The investigators believe that treatment of HCV is now well within the grasp of physicians and other healthcare providers without training in internal or family medicine. This single arm pilot study will assess HCV treatment with Epclusa at an outpatient addiction clinic staffed by psychiatrists. The investigators hypothesize that with proper training and mentorship, psychiatrists who are also a licensed buprenorphine/naloxone providers will be able to effectively assess liver health and treat chronic hepatitis C infection with Epclusa. Further, the investigators hypothesize that patients with chronic hepatitis C infection on buprenorphine/naloxone maintenance therapy who are treated for HCV by a psychiatrist during regularly scheduled visits to an addiction clinic will have high rates of adherence to HCV treatment and achieve SVR12 (sustained virologic response, 12 weeks post-treatment). Given that subjects will receive standard of care evaluation and treatment for their chronic hepatitis C infection, the investigators believe that study participation poses minimal risk. Indeed, The investigators believe that subjects will benefit from improved access to this important treatment which will be provided at a convenient location by a known physician under the guidance of an infectious disease physician with extensive experience treating HCV infection.

Official Title
-----------------
Bridging Care to HCV Treatment Among Opiate Dependent Patients on Buprenorphine/Naloxone Maintenance Therapy: A Pilot Study of Treating HCV With Epclusa at a Psychiatrist-staffed Outpatient Addiction Clinic

Conditions
-----------------
Hepatitis C, Chronic, Hepatitis C, Opiate Dependence

Intervention / Treatment
-----------------
* Drug: sofosbuvir/velpatasvir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing and able to provide written informed consent Age ≥ 18 years Confirmation of chronic HCV infection as documented by a positive HCV antibody test at least 6 months prior to the Baseline/Day 1 visit and positive HCV RNA test at screening HCV genotype 1, 2, 3, 4, 5 or 6 In stable remission from opiate use on buprenorphine/naloxone for at least 12 weeks Within the following laboratory parameters as assessed at the screening visit: HCV RNA quantifiable Screening rhythm strip without bradycardia (heart rate > 60 or, if on beta blocker, > 55 BPM) Alanine Aminotransferase (ALT) ≤ 10 x ULN (upper limit of normal) Aspartate Aminotransferase (AST) ≤ 10 x ULN Direct bilirubin ≤ 1.5 x ULN Platelets > 60,000 Hemoglobin A1C (HbA1c) ≤ 10% Creatinine clearance ≥ 30 mL/min, as calculated by the Cockcroft-Gault equation Albumin ≥ 3g/dL International Normalized Ratio (INR) ≤ 1.5 x ULN or on an anticoagulant regimen affecting INR Female subject is eligible to enter if it is confirmed that she is: Not pregnant or nursing Not of childbearing potential (i.e. s/p hysterectomy, oophorectomy or has medically documented ovarian failure, or are postmenopausal women > 50 years of age with cessation of menses for 12 months or greater) OR Of childbearing potential with a negative serum pregnancy test within 2 weeks of screening, a negative urine pregnancy test on Day 1, and a commitment to either abstain from intercourse or consistently use an acceptable method of birth control (Appendix 4) in addition to condom use by her male partner(s) from the date of screening until 30 days after the last dose of study drug All male study participants must agree to consistently and correctly use condoms with their female partner(s) and their female partner(s) must agree to use an acceptable method of birth control (listed) from the date of screening until 90 days after the last dose of study drug Male subjects must refrain from sperm donation from the date of screening until 90 days after the last dose of study drug Subject must be in generally good health, with the exception of HCV, in the opinion of the Sponsor-Investigator or Sub-Investigator(s) Subject must be able to comply with dosing instructions for study drug administration and able to complete the study visits, including all required post-treatment visits Exclusion Criteria: Presence of decompensated cirrhosis as defined by encephalopathy, ascites, or a history of a variceal bleed Prior treatment with direct acting antiviral hepatitis C medications Positive urine drug toxicity test at screening (except for cannabinoids and prescribed medications) Absence of buprenorphine in urine sample at screening Currently pregnant or breastfeeding female Detectable HIV RNA > 50 copies/ml (co-infected subjects with suppressed viral load are eligible for participation) Use of any prohibited concomitant medication within 28 days prior to day 1 Chronic use of systemically administered immunosuppressive agents Difficulty with blood collection or poor venous access History of solid organ transplantation Known significant allergy to sofosbuvir or velpatasvir Current chronic liver disease of a non-HCV etiology (including hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency) Active Hepatitis B virus (HBV) infection defined as either a positive HBV surface antigen test or a positive test for HBV DNA. (Subjects who are positive for HBV core antibody but negative for Hepatitis B surface antibody, surface antigen, and DNA ARE eligible)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Arm<br>In this open label, single arm study, all subjects will receive the intervention as prescribed by psychiatrists in the office based opiate addition treatment program. | Drug: sofosbuvir/velpatasvir<br>* 12 week treatment with once daily sofosbuvir/velpatasvir fixed dose combination therapy. Tablets are formulated with 400mg sofosbuvir and 100mg velpatasvir in pink, diamond-shaped, film coated tablets.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment (SVR-12) | To assess the effectiveness of HCV treatment with velpatasvir/sofosbuvir administered by psychiatrist/licensed buprenorphine/naloxone providers during regularly scheduled visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental healthcare, as measured by percentage of patients achieving SVR-12 (defined as HCV RNA < lower limit of quantification (LLOQ) 12 weeks after discontinuation of study treatment), | This outcome measure will be assessed for each participant 12 weeks after completion of a 12 week course of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health-Related Quality of Life | Change in mean score on 5-point LIkert Scale to statement My Health is Excellent (1=definitely true, 5=definitely false) from baseline and 12 weeks post-treatment | Baseline and 12 weeks post treatment | 
| Adherence to Study Treatment | To assess adherence to velpatasvir/sofosbuvir therapy among participants administered treatment in the context of visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental health care. | This outcome measure will be assessed for each participant during a 12 week course of study treatment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HCV, Suboxone, Epclusa, psychiatrist