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

NCT02609893 | Completed Phase 4 DMC

• 1 other identifier: 1R34DA039333
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis C

Keywords

HCV

Outcome Measures

Primary Outcomes (3)

• Number of people who inject drugs (PWIDs) with HCV who were recruited and retained

  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.

  44 weeks

• Medication adherence to study drug

  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.

  44 weeks

• Challenges of medication adherence

  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.

  44 weeks

Secondary Outcomes (4)

• SVR (end-of-treatment response)

  12 weeks

• SOF/metabolite levels

  8 weeks

• HCV relapse and reinfection

  36 weeks

• Social and injector networks of participants

  44 weeks

Study Arms (2)

Modified Directly Observed Therapy

ACTIVE COMPARATOR

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

Unobserved Dosing

ACTIVE COMPARATOR

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

Interventions

modified directly observed therapy (mDOT) OTHER

Modified Directly Observed Therapy

unobserved dosing OTHER

Unobserved Dosing

Motivational Interviewing-based counseling OTHER

Motivational Interviewing-based risk reduction and medication adherence counseling

Modified Directly Observed Therapy; Unobserved Dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age;
• consecutive positive HCV RNA tests at least 6 months after estimated date of infection;
• HCV genotype 1;
• HCV RNA \<6 million copies by Roche TaqMan Assay
• 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 \[sensitivity/specificity 86/100%\]);
• Drug injection in past 30 days by self-report and physical exam evidence of injection drug use (e.g. track marks),
• injected with others in past 12 months by self-report;
• 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);
• Able to speak English;
• 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;
• 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).

You may not qualify if:

• HIV+ by rapid test or pooled viral load;
• HBV surface antigen +;
• Non-definitive HCV genotype results;
• Previously received treatment for HCV (interferon, ribavirin, or DAA);
• Taking medications that affect pharmacokinetics of LDV-SOF (proton-pump inhibitors, anticonvulsants \[phenobarbital, phenytoin, carbamazepine, oxcarbazepine\], rifamycins, rosuvastatin, herbs \[St. John's wort, silymarin, echinacea\]);
• History of any of the following:
• Current gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug
• History of hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)
• History of solid organ or bone marrow transplantation.
• Current treatment for cancer
• Chronic liver disease for non HCV reason, except iron overload (e.g., Wilson's disease, alfa 1 antitrypsin deficiency, cholangitis);
• Use of any prohibited concomitant medications as described in Section 5.2 within 21 days of the Day 1 visit; and
• Known hypersensitivity to LDV, SOF, the metabolites, or formulation excipients.
• No other conditions that preclude study involvement as determined by PI.

Sponsors & Collaborators

• Phillip Coffin, MD, MIA: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Substance Use Research Unit

San Francisco, California, 94102, United States

Location

Related Publications (1)

• 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.

  PMID: 31158245 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Phillip O Coffin, M.D.

  San Francisco Department of Public Health

  PRINCIPAL INVESTIGATOR

• Emily Behar, MS

  San Francisco Department of Public Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Substance Use Research Unit

Study Record Dates

• First Submitted: October 5, 2015
• First Posted: November 20, 2015
• Study Start: December 1, 2015
• Primary Completion: April 1, 2018
• Study Completion: August 1, 2019
• Last Updated: October 22, 2020

Record last verified: 2020-10

Locations

US (1)