Pilot Treatment as Prevention for HCV Among Persons Who Actively Inject Drugs (BYE-C)

• ClinicalTrials.gov Identifier: NCT02609893
• Recruitment Status: Unknown
• First Posted: November 20, 2015
• Last Update Posted: September 26, 2017
• Sponsor: Phillip Coffin, MD, MIA
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Phillip Coffin, MD, MIA, San Francisco Department of Public Health

Study Description

Brief Summary:

This project is a randomized trial of two strategies to treat persons with genotype 1 HCV who currently inject drugs (PWIDs) with a once daily regime of ledipasvir-sofosbuvir (LDV-SOF) for 8 weeks. The study will enroll 30 participants and will assess the feasibility and acceptability of treating active PWIDs for HCV with LDV-SOF by modified directly observed therapy (mDOT) versus unobserved dosing, with motivational interviewing based adherence support; and assess through in-depth, semi-structured qualitative interviews, the challenges with time intensity required for mDOT and unobserved dosing interventions, and identify key factors affecting treatment adherence.

Condition or disease	Intervention/treatment	Phase
Chronic Hepatitis C	Other: modified directly observed therapy (mDOT); Other: unobserved dosing; Other: Motivational Interviewing-based counseling	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Treatment as Prevention for HCV Among Persons Who Actively Inject Drugs
• Study Start Date: December 2015
• Estimated Primary Completion Date: May 2018
• Estimated Study Completion Date: May 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Modified Directly Observed Therapy; Ledipasvir/Sofosbuvir Fixed-Dose Combination (LDV-SOF) tablet (LDV 90mg/SOF 400mg) observed daily dosing (modified for non-observed Saturday and Sunday dosing) for 8 weeks	Other: modified directly observed therapy (mDOT); Other: Motivational Interviewing-based counseling; Motivational Interviewing-based risk reduction and medication adherence counseling
Active Comparator: Unobserved Dosing; Ledipasvir/Sofosbuvir Fixed-Dose Combination (LDV-SOF) tablet (LDV 90mg/SOF 400mg) provided weekly (7 tablets) for unobserved daily dosing for 8 weeks	Other: unobserved dosing; Other: Motivational Interviewing-based counseling; Motivational Interviewing-based risk reduction and medication adherence counseling

Outcome Measures

Primary Outcome Measures :

1. Number of people who inject drugs (PWIDs) with HCV who were recruited and retained [ Time Frame: 44 weeks ]
   To determine the feasibility of treating active PWIDs for HCV with LDV-SOF by mDOT versus unobserved dosing based on proportion eligible and enrolled among those screened and completion rates overall and by arm.
2. Medication adherence to study drug [ Time Frame: 44 weeks ]
   To evaluate the acceptability of mDOT versus unobserved dosing, the percent of treatment medication adherence to LDV-SOF, as measured by the percent of doses taken overall (observed and unobserved), will be assessed using DOT doses and weekend Wise Pill data for the mDOT arm, and WisePill data for the unobserved dosing arm.
3. Challenges of medication adherence [ Time Frame: 44 weeks ]
   To assess through in-depth, semi-structured qualitative interviews, the challenges with time intensity required for mDOT versus unobserved dosing for PWIDs treated with LDV-SOF.

Secondary Outcome Measures :

1. SVR (end-of-treatment response) [ Time Frame: 12 weeks ]
   We will compare the proportion of participants with undetectable HCV RNA at week 8 and post-treatment week 12 between arms.
2. SOF/metabolite levels [ Time Frame: 8 weeks ]
   SOF/metabolite-positivity rates will be calculated by week in both arms.
3. HCV relapse and reinfection [ Time Frame: 36 weeks ]
   Among participants who achieve SVR, we will determine the proportion who experience HCV relapse and reinfection at post-treatment week 36, overall and by arm.
4. Social and injector networks of participants [ Time Frame: 44 weeks ]
   We will characterize injector network sizes at baseline and follow-up through ACASI surveys.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. ≥18 years of age;
2. 2 consecutive positive HCV RNA tests at least 6 months after estimated date of infection;
3. HCV genotype 1;
4. HCV RNA <6 million copies by Roche TaqMan Assay
5. No evidence of hepatic cirrhosis (as determined by two indices: Fib4<3.25—an accurate test for detecting cirrhosis based on age, AST, ALT and platelets [sensitivity/specificity 76-100/82-91%], confirmed by the fibrosis-cirrhosis index (FCI)<1.25 based on ALT, bilirubin, albumin and platelets [sensitivity/specificity 86/100%]);
6. Drug injection in past 30 days by self-report and physical exam evidence of injection drug use (e.g. track marks),
7. injected with others in past 12 months by self-report;
8. Lab values within acceptable range (platelets>50,000, creatinine clearance by Cockroft-Gault>30mL/min, hemoglobin >10g/dL, INR<1.5 x upper limit of normal (ULN) unless stable on anticoagulant regimen or known hemophilia, AST/ALT<10 x ULN);
9. Able to speak English;
10. No plans to leave San Francisco area for at least 9 months and either lives or works in San Francisco, or travels to San Francisco at least weekly;
11. for women of childbearing age, pregnancy test negative, not actively nursing, and agree to use birth control during treatment (although LDV-SOF has a "B" rating, consistent with no known evidence of harm, treatment is not urgent for these patients so we will err on the side of caution).

Exclusion Criteria:

1. HIV+ by rapid test or pooled viral load;
2. HBV surface antigen +;
3. Non-definitive HCV genotype results;
4. Previously received treatment for HCV (interferon, ribavirin, or DAA);
5. Taking medications that affect pharmacokinetics of LDV-SOF (proton-pump inhibitors, anticonvulsants [phenobarbital, phenytoin, carbamazepine, oxcarbazepine], rifamycins, rosuvastatin, herbs [St. John's wort, silymarin, echinacea]);

6. History of any of the following:

   1. Current gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug
   2. History of hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)
   3. History of solid organ or bone marrow transplantation.
   4. Current treatment for cancer
7. Chronic liver disease for non HCV reason, except iron overload (e.g., Wilson's disease, alfa 1 antitrypsin deficiency, cholangitis);
8. Use of any prohibited concomitant medications as described in Section 5.2 within 21 days of the Day 1 visit; and
9. Known hypersensitivity to LDV, SOF, the metabolites, or formulation excipients.
10. No other conditions that preclude study involvement as determined by PI.

Contacts and Locations

Locations

United States, California

Substance Use Research Unit

San Francisco, California, United States, 94102

Sponsors and Collaborators

Phillip Coffin, MD, MIA

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Phillip O Coffin, M.D.; San Francisco Department of Public Health
• Study Director: Emily Behar, MS; San Francisco Department of Public Health

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Coffin PO, Santos GM, Behar E, Hern J, Walker J, Matheson T, Kinnard EN, Silvis J, Vittinghoff E, Fox R, Page K. Randomized feasibility trial of directly observed versus unobserved hepatitis C treatment with ledipasvir-sofosbuvir among people who inject drugs. PLoS One. 2019 Jun 3;14(6):e0217471. doi: 10.1371/journal.pone.0217471. eCollection 2019.

• Responsible Party: Phillip Coffin, MD, MIA, Director, Substance Use Research Unit, San Francisco Department of Public Health
• ClinicalTrials.gov Identifier: NCT02609893
• Other Study ID Numbers: 1R34DA039333 ( U.S. NIH Grant/Contract )
• First Posted: November 20, 2015
• Last Update Posted: September 26, 2017
• Last Verified: September 2017

Keywords provided by Phillip Coffin, MD, MIA, San Francisco Department of Public Health:

HCV

Additional relevant MeSH terms:

Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic