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

Phillip Coffin, MD, MIA

Status and phase: Completed; Phase 4

Conditions: Chronic Hepatitis C

Treatments: Other: Motivational Interviewing-based counseling; Other: modified directly observed therapy (mDOT); Other: unobserved dosing

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02609893

1R34DA039333

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 2 patient groups

Modified Directly Observed Therapy

Active Comparator group

Description:

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

Treatment:

Other: Motivational Interviewing-based counseling

Other: modified directly observed therapy (mDOT)

Unobserved Dosing

Active Comparator group

Description:

Ledipasvir/Sofosbuvir Fixed-Dose Combination (LDV-SOF) tablet (LDV 90mg/SOF 400mg) provided weekly (7 tablets) for unobserved daily dosing for 8 weeks

Treatment:

Other: unobserved dosing

Other: Motivational Interviewing-based counseling