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

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 (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 SVR 12.

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.

Inclusion Criteria:

1. Willing and able to provide written informed consent

2. Age ≥ 18 years

3. 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

4. HCV genotype 1, 2, 3, 4, 5 or 6

5. In stable remission from opiate use on buprenorphine/naloxone for at least 12 weeks

6. Within the following laboratory parameters as assessed at the screening visit:

1. HCV RNA quantifiable

2. Screening rhythm strip without bradycardia (heart rate > 60 or, if on beta
blocker, > 55 BPM)

3. Alanine Aminotransferase (ALT) ≤ 10 x ULN (upper limit of normal)

4. Aspartate Aminotransferase (AST) ≤ 10 x ULN

5. Direct bilirubin ≤ 1.5 x ULN

6. Platelets > 60,000

7. Hemoglobin A1C (HbA1c) ≤ 10%

8. Creatinine clearance ≥ 30 mL/min, as calculated by the Cockcroft-Gault equation

9. Albumin ≥ 3g/dL

10. International Normalized Ratio (INR) ≤ 1.5 x ULN or on an anticoagulant regimen
affecting INR

7. Female subject is eligible to enter if it is confirmed that she is:

1. Not pregnant or nursing

2. 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

8. 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

9. Male subjects must refrain from sperm donation from the date of screening until 90
days after the last dose of study drug

10. Subject must be in generally good health, with the exception of HCV, in the opinion of
the Sponsor-Investigator or Sub-Investigator(s)

11. 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:

1. Presence of decompensated cirrhosis as defined by encephalopathy, ascites, or a
history of a variceal bleed

2. Prior treatment with direct acting antiviral hepatitis C medications

3. Positive urine drug toxicity test at screening (except for cannabinoids and prescribed
medications)

4. Absence of buprenorphine in urine sample at screening

5. Currently pregnant or breastfeeding female

6. Detectable HIV RNA > 50 copies/ml (co-infected subjects with suppressed viral load ARE
eligible for participation)

7. Use of any prohibited concomitant medication within 28 days prior to day 1

8. Chronic use of systemically administered immunosuppressive agents

9. Difficulty with blood collection or poor venous access

10. History of solid organ transplantation

11. Known significant allergy to sofosbuvir or velpatasvir

12. Current chronic liver disease of a non-HCV etiology (including hemochromatosis,
Wilson's disease, alfa-1 antitrypsin deficiency)

13. 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)