Pilot Treatment as Prevention for HCV Among Persons Who Actively Inject Drugs

Phase 4

Completed

• Conditions: Chronic Hepatitis C
• Interventions: Other: modified directly observed therapy (mDOT); Other: unobserved dosing; Other: Motivational Interviewing-based counseling

• Registration Number: NCT02609893
• Lead Sponsor: Phillip Coffin, MD, MIA

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-10-05
• Study First Submitted QC: 2015-11-17
• Study First Posted: 2015-11-20
• Study Start: 2015-12
• Primary Completion: 2018-04
• Study Completion: 2019-08
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-20
• Last Update Posted: 2020-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Modified Directly Observed Therapy	modified directly observed therapy (mDOT)	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
Unobserved Dosing	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
Modified Directly Observed Therapy	Motivational Interviewing-based counseling	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
Unobserved Dosing	Motivational Interviewing-based counseling	Ledipasvir/Sofosbuvir Fixed-Dose Combination (LDV-SOF) tablet (LDV 90mg/SOF 400mg) provided weekly (7 tablets) for unobserved daily dosing for 8 weeks

Primary Outcome Measures

Name	Time	Method
Number of people who inject drugs (PWIDs) with HCV who were recruited and retained	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.
Medication adherence to study drug	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.
Challenges of medication adherence	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

Name	Time	Method
SVR (end-of-treatment response)	12 weeks	We will compare the proportion of participants with undetectable HCV RNA at week 8 and post-treatment week 12 between arms.
SOF/metabolite levels	8 weeks	SOF/metabolite-positivity rates will be calculated by week in both arms.
Social and injector networks of participants	44 weeks	We will characterize injector network sizes at baseline and follow-up through ACASI surveys.
HCV relapse and reinfection	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.

Trial Locations

Locations (1)

Substance Use Research Unit; 🇺🇸 San Francisco, California, United States