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

Sponsor
Community Research Initiative of New England (Other)
Overall Status
Completed
CT.gov ID
NCT03235154
Collaborator
Gilead Sciences (Industry)
11
Enrollment
1
Location
1
Arm
23.5
Actual Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
11 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 11, 2017
Actual Primary Completion Date :
Sep 26, 2019
Actual Study Completion Date :
Sep 26, 2019

Arms and Interventions

ArmIntervention/Treatment
Other: Treatment Arm

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
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.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment (SVR-12) [This outcome measure will be assessed for each participant 12 weeks after completion of a 12 week course of treatment]

    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),

Secondary Outcome Measures

  1. Health-Related Quality of Life [Baseline and 12 weeks post treatment]

    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

  2. Adherence to Study Treatment [This outcome measure will be assessed for each participant during a 12 week course of 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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:

  7. HCV RNA quantifiable

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

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

  10. Aspartate Aminotransferase (AST) ≤ 10 x ULN

  11. Direct bilirubin ≤ 1.5 x ULN

  12. Platelets > 60,000

  13. Hemoglobin A1C (HbA1c) ≤ 10%

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

  15. Albumin ≥ 3g/dL

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

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

  18. Not pregnant or nursing

  19. 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

  1. 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
  1. 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

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

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

  4. 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)

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Cambridge Health Alliance Outpatient Addiction ServicesSomervilleMassachusettsUnited States02143

Sponsors and Collaborators

  • Community Research Initiative of New England
  • Gilead Sciences

Investigators

  • Principal Investigator: Amy E Colson, MD MPH, Community Research Initiative of New England

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Community Research Initiative of New England
ClinicalTrials.gov Identifier:
NCT03235154
Other Study ID Numbers:
  • 15-05
First Posted:
Aug 1, 2017
Last Update Posted:
May 13, 2021
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Community Research Initiative of New England
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleTreatment Arm
Arm/Group DescriptionIn this open label, single arm study, all subjects will receive the intervention as prescribed by psychiatrists in the office based opiate addition treatment program. sofosbuvir/velpatasvir: 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.
Period Title: Overall Study
STARTED11
Completed Epclusa. Treatment8
12-wk Post-treatment HCV RNA Measured7
COMPLETED7
NOT COMPLETED4

Baseline Characteristics

Arm/Group TitleSingle Arm Intervention
Arm/Group Description12-week Epclusa Treatment
Overall Participants11
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]
48
Sex: Female, Male (Count of Participants)
Female
7
63.6%
Male
4
36.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
Not Hispanic or Latino
9
81.8%
Unknown or Not Reported
2
18.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
Asian
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
Black or African American
1
9.1%
White
9
81.8%
More than one race
0
0%
Unknown or Not Reported
1
9.1%
Region of Enrollment (participants) [Number]
United States
11
100%
Co-morbid axis 1 diagnosis present (Count of Participants)
Count of Participants [Participants]
11
100%
HCV (hepatitis C virus) RNA (IU/ml) [Mean (Full Range) ]
Mean (Full Range) [IU/ml]
2,662,207
Baseline FibroSure fibrosis stage (Count of Participants)
F0
6
54.5%
F1
2
18.2%
F2
0
0%
F3
1
9.1%
F4
0
0%
Unknown
2
18.2%

Outcome Measures

1. Primary Outcome
TitlePercentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment (SVR-12)
DescriptionTo 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),
Time FrameThis outcome measure will be assessed for each participant 12 weeks after completion of a 12 week course of treatment

Outcome Measure Data

Analysis Population Description
subjects who completed Epclusa treatment and had HCV RNA measured 12 weeks after completion of treatment
Arm/Group TitleTreatment Arm
Arm/Group DescriptionIn this open label, single arm study, all subjects will receive the intervention as prescribed by psychiatrists in the office based opiate addition treatment program. sofosbuvir/velpatasvir: 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.
Measure Participants7
Count of Participants [Participants]
7
63.6%
2. Secondary Outcome
TitleHealth-Related Quality of Life
DescriptionChange 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
Time FrameBaseline and 12 weeks post treatment

Outcome Measure Data

Analysis Population Description
Subjects who completed questionnaire at baseline and 12 weeks after completion of treatment
Arm/Group TitleSingle Arm Intervention
Arm/Group DescriptionSubjects who completed baseline and 12-week post treatment questionnaire
Measure Participants7
Mean (Full Range) [score on a scale]
-0.44
3. Secondary Outcome
TitleAdherence to Study Treatment
DescriptionTo 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.
Time FrameThis outcome measure will be assessed for each participant during a 12 week course of study treatment.

Outcome Measure Data

Analysis Population Description
The 8 subjects who completed treatment
Arm/Group TitleSingle Arm Intervention
Arm/Group Description12-week Epclusa Treatment
Measure Participants8
Mean (Full Range) [% of prescribed doses taken]
94
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Arm
Comments This was a single arm intervention study with a very small number of participants. Therefore, only descriptive statistics are provided.
Type of Statistical Test Other
Comments There was no comparator arm in this small single arm study
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Other Statistical AnalysisNo confidence intervals around point estimates provided given very small number of participants

Adverse Events

Time FrameFrom study entrance through treatment period
Adverse Event Reporting Description
Arm/Group TitleSingle Arm Intervention
Arm/Group Description12-week Epclusa Treatment
All Cause Mortality
Single Arm Intervention
Affected / at Risk (%)# Events
Total0/11 (0%)
Serious Adverse Events
Single Arm Intervention
Affected / at Risk (%)# Events
Total3/11 (27.3%)
Nervous system disorders
Altered Mental Status1/11 (9.1%) 1
Seizure1/11 (9.1%) 1
Visual Hallucination1/11 (9.1%) 1
Psychiatric disorders
Suicidal Ideation1/11 (9.1%) 1
Other (Not Including Serious) Adverse Events
Single Arm Intervention
Affected / at Risk (%)# Events
Total3/11 (27.3%)
Gastrointestinal disorders
GI distress2/11 (18.2%)
Nervous system disorders
Fatigue1/11 (9.1%)
Skin and subcutaneous tissue disorders
Scabies1/11 (9.1%)

Limitations/Caveats

Small number of subjects analyzed

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleAmy E. Colson, MD
OrganizationCommunity Research Initiative of New England
Phone6175021700
Emailacolson@crine.org
Responsible Party:
Community Research Initiative of New England
ClinicalTrials.gov Identifier:
NCT03235154
Other Study ID Numbers:
  • 15-05
First Posted:
Aug 1, 2017
Last Update Posted:
May 13, 2021
Last Verified:
Apr 1, 2021