Clinical trial NCT02609893: Pilot Treatment as Prevention for HCV Among Persons Who Actively Inject Drugs
Official title: Pilot Treatment as Prevention for HCV Among Persons Who Actively Inject Drugs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis C
Keywords: HCV
Lead sponsor: San Francisco Department of Public Health
Sponsor class: OTHER_GOV
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2015-11-20
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of people who inject drugs (PWIDs) with HCV who were recruited and retained
timeFrame: 44 weeks
measure: Medication adherence to study drug
timeFrame: 44 weeks
measure: Challenges of medication adherence
timeFrame: 44 weeks
Secondary outcomes:
measure: SVR (end-of-treatment response)
timeFrame: 12 weeks
measure: SOF/metabolite levels
timeFrame: 8 weeks
measure: HCV relapse and reinfection
timeFrame: 36 weeks
measure: Social and injector networks of participants
timeFrame: 44 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Substance Use Research Unit
state: California
Study officials:
affiliation: San Francisco Department of Public Health
name: Phillip O Coffin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: San Francisco Department of Public Health
name: Emily Behar, MS
role: STUDY_DIRECTOR
References:
citation: 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.