Phase 2
N=128
A Direct obserVed therApy vs fortNightly CollEction Study for HCV Treatment - ADVANCE HCV Study
Hepatitis C
Bottom Line
View on ClinicalTrials.gov: NCT03236506 ↗Enrolled (actual)
128
Serious AEs
18.0%
Results posted
Nov 2021
Primary outcome: Primary: Comparison of Sustained Viral Response at 12 Weeks Post Treatment (SVR12) in the Three Treatment Groups. — 3; 5; 3; 30 Participants — p=0.67
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet (Drug); Psychological intervention (Behavioral); Sofosbuvir 400 MG (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Dundee
- Primary completion
- Aug 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Comparison of Sustained Viral Response at 12 Weeks Post Treatment (SVR12) in the Three Treatment Groups. |
3; 5; 3; 30; 32; 37 | 0.67 |
| SECONDARY Adherence as Assessed by the Total Percentage of Tablets Taken (Out of Those Dispensed) During the Treatment Period |
69; 96; 98 | — |
| SECONDARY Assessment of Reinfection Rates in Active PWIDs Treated With Oral DAA Regimes |
— | — |
| SECONDARY Assessment of Resistance Profiles in Those Who do Not Achieve SVR |
— | — |
| SECONDARY Assessment of the Types of Illicit Drugs Taken by Trial Participants and Identification of Any Interaction With the Directly Acting Therapies. |
— | — |
Summary
Hepatitis C is a blood borne virus that can seriously damage the liver. An estimated 50,000 Scots have been infected with Hepatitis C virus (HCV). The main driver for spread of HCV infection is intravenous drug use. As HCV is highly infectious by the blood borne route through needle sharing, it can infect the person who injects drugs (PWID) early in their habit.
Around two thirds of people who are infected are unaware of it, and often show no symptoms over a long period of time. While there is presently no vaccination for Hepatitis C, improved treatments with shorter duration are now available. This raises the possibility of using therapy as prevention, turning the epidemic off at source, by targeting active PWID who are the main source of new infections. Modelling work illustrates the startling possibility and impact of treating drug users to reduce the prevalence of HCV.
The focus of this trial will be to ascertain whether oral treatment regimens are effective in the treatment as prevention scenario in an active PWID population where illicit drug taking and poor adherence may reduce treatment efficacy. The investigators will trial 3 different methods of delivering treatment and will trial an unlicensed combined treatment against HCV genotype 3 infection of shortened duration since current regimens for this genotype are limited.
The investigators will recruit 135 participants and randomise them to one of three arms: daily, directly observed therapy; fortnightly dispensing of drugs; fortnightly dispensing of drugs with a psychological adherence intervention. Randomisation will be stratified according to HCV genotype. Participants will be treated for 12 or 8 weeks depending on genotype and followed up 12 weeks post treatment for the measurement of sustained viral response (SVR). The primary outcome measure will be SVR at 12 weeks post treatment (SVR12), as this measure of cure is the determinant of sufficient compliance and efficacy within the 3 treatment arms. Analysis will be by modified intention to treat of all participants who receive one dose of therapy, to show non-inferiority fortnightly dispensing is easier to deliver than daily dispensing.
Eligibility Criteria
Inclusion Criteria
- Male or Female. (Age limit 18-70)
- HCV PCR confirmed active infection, genotype 1 or 3.
- If female, must have negative urine test results for pregnancy during initial screening period (for trial inclusion) and be advised of limited safety data in pregnancy.
- Current illicit drug use established through participant history.
- Able to provide informed consent, agreeing to trial and clinical monitoring criteria
Exclusion Criteria
- Aggressive or violent behaviour.
- Platelet count 350 Units/l
- Inability to provide informed consent.
- Clinical history or abnormal valves for albumin 35 umol/l or prothrombin time >1.5 consistent with decompensated liver failure Childs-Pugh B or C
- Clinical history of primary hepatocellular carcinoma
- Pregnancy or breast feeding.
- Participation in a drug trial within the previous 30 days
- Hepatitis B surface antigen positive
- HIV infection.
- Hypersensitivity to elbasvir and grazoprevir
- Hypersensitivity to sofosbuvir (genotype 3 infected-participants ony)
- Currently being treated with an inhibitor of organic anion transporting polypeptide 1B, e.g. rifampicin, atazanavir, daruavir, lopinavir, saquinavir, tipranavir, cobicistat or ciclosporin.
- Currently being treated with inducers of cytochrome P450 3A or P-glycoprotein, such as efavirenz, phenytoin, carbamazepine, bosentan, etravirine, modafinil or St John's Wort (Hypericum perforatum)
- Currently being treated with amiodarone (Participants infected with genotype 3 HCV only)
Data sourced from ClinicalTrials.gov (NCT03236506). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.