A Direct obserVed therApy vs fortNightly CollEction Study for HCV Treatment - ADVANCE HCV Study

NCT03236506 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2016GA032017-001039-38
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Hepatitis C

Keywords

Illicit drug; Injecting drug

Outcome Measures

Primary Outcomes (1)

• Comparison of Sustained Viral Response at 12 Weeks Post Treatment (SVR12) in the Three Treatment Groups.

  SVR12 of participants in the directly observed therapy (DOT), fortnightly pick-up or fortnightly pick-up with a psychological adherence intervention group. SVR12 was measured by viral load of hepatitis c virus (HCV) in participant's blood at least 12 weeks after end of treatment. A viral load of less than 10IU/ml indicates no active infection and SVR12 has been achieved.

  24 weeks for genotype 1 HCV, 20 weeks for genotype 3 HCV infection

Secondary Outcomes (4)

• Adherence as Assessed by the Total Percentage of Tablets Taken (Out of Those Dispensed) During the Treatment Period

  12 weeks for genotype 1 HCV, 8 weeks for genotype 3 HCV infection

• Assessment of Reinfection Rates in Active PWIDs Treated With Oral DAA Regimes

  Not applicable. Not part of study data set.

• Assessment of Resistance Profiles in Those Who do Not Achieve SVR

  Bloods collected at baseline, end of treatment and 12 weeks post end of treatment

• Assessment of the Types of Illicit Drugs Taken by Trial Participants and Identification of Any Interaction With the Directly Acting Therapies.

  At three timepoints; time zero (before treatment), time 2-8 weeks (during treatment) time 12 weeks (at the end of treatment)

Study Arms (3)

Daily observed therapy

EXPERIMENTAL

Patients with active hepatitis C infection genotype 1 will receive 12 weeks treatment with Zepatier at one tablet per day. Patients with active hepatitis C infection genotype 3 will receive 8 weeks treatment with Zepatier pill plus Sofosbuvir pill at one of each tablets per day. These tablets will be given to patients on a daily, observed basis by either the nurse or a community pharmacist.

Drug: Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet; Drug: Sofosbuvir 400 MG

Fortnightly pick-up

ACTIVE COMPARATOR

Patients with active hepatitis C infection genotype 1 will receive 12 weeks treatment with Zepatier at one tablet per day. Patients with active hepatitis C infection genotype 3 will receive 8 weeks treatment with Zepatier pill plus Sofosbuvir pill at one of each tablets per day. These tablets will be given to patients on a fortnightly basis by the nurse.

Drug: Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet; Drug: Sofosbuvir 400 MG

Fortnightly pick-up +psych intervention

ACTIVE COMPARATOR

Patients with active hepatitis C infection genotype 1 will receive 12 weeks treatment with Zepatier at one tablet per day. Patients with active hepatitis C infection genotype 3 will receive 8 weeks treatment with Zepatier pill plus Sofosbuvir pill at one of each tablets per day. These tablets will be given to patients on a fortnightly basis by the nurse. In addition, this group will receive a one-off interview with the researcher to complete a psychological intervention designed to improve adherence to the medication regimen.

Drug: Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet; Behavioral: Psychological intervention; Drug: Sofosbuvir 400 MG

Interventions

Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet DRUG

Drugs will be given to participants to treat hepatitis C infection

Also known as: Zepatier

Daily observed therapy; Fortnightly pick-up; Fortnightly pick-up +psych intervention

Psychological intervention BEHAVIORAL

Participants randomised to fortnightly pick-up with psychological intervention will have an interview with the study nurse designed to aid their compliance with the drug regimen. During the intervention participants will be guided by their trial nurse in the completion of a personalised booklet, "Hepatitis C and Me". The booklet uses the principles of node-link mapping to structure the intervention.

Fortnightly pick-up +psych intervention

Sofosbuvir 400 MG DRUG

Drugs will be given along with Zepatier to participants to treat genotype 3hepatitis C infection

Also known as: Sovaldi

Daily observed therapy; Fortnightly pick-up; Fortnightly pick-up +psych intervention

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female. (Age limit 18-70)
• HCV PCR confirmed active infection, genotype 1 or 3.
• Current illicit drug use established through participant history.
• Able to provide informed consent, agreeing to trial and clinical monitoring criteria

You may not qualify if:

• Aggressive or violent behaviour.
• Platelet count \< 75000000000 /ml
• Alanine transaminase \> 350 Units/l
• Inability to provide informed consent.
• Clinical history or abnormal valves for albumin\< 30 g/l, Bilirubin \>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)

Sponsors & Collaborators

• University of Dundee: lead

Study Sites (2)

University of Dundee

Dundee, Tayside, DD1 9SY, United Kingdom

Location

NHS Tayside

Dundee, DD1 9SY, United Kingdom

Location

Related Publications (2)

• Beer L, Inglis S, Malaguti A, Byrne C, Sharkey C, Robinson E, Gillings K, Radley A, Hapca A, Stephens B, Dillon J. Randomized clinical trial: Direct-acting antivirals as treatment for hepatitis C in people who inject drugs: Delivered in needle and syringe programs via directly observed therapy versus fortnightly collection. J Viral Hepat. 2022 Aug;29(8):646-653. doi: 10.1111/jvh.13701. Epub 2022 May 26.

  PMID: 35582875 DERIVED

• Inglis SK, Beer LJ, Byrne C, Malaguti A, Robinson E, Sharkey C, Gillings K, Stephens B, Dillon JF. Randomised controlled trial conducted in injecting equipment provision sites to compare the effectiveness of different hepatitis C treatment regimens in people who inject drugs: A Direct obserVed therApy versus fortNightly CollEction study for HCV treatment-ADVANCE HCV protocol study. BMJ Open. 2019 Aug 8;9(8):e029516. doi: 10.1136/bmjopen-2019-029516.

  PMID: 31399460 DERIVED

MeSH Terms

Conditions

Hepatitis C; Substance-Related Disorders

Interventions

elbasvir; grazoprevir; elbasvir-grazoprevir drug combination; Psychosocial Intervention; Sofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities; Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Professor John Dillon
• Organization: University of Dundee

j.f.dillon@dundee.ac.uk

01382 383017

Study Officials

• John Dillon, MD

  University of Dundee

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor John Dillon

Model Details: Randomised, un-blinded trial

Study Record Dates

• First Submitted: July 4, 2017
• First Posted: August 2, 2017
• Study Start: January 19, 2018
• Primary Completion: August 31, 2020
• Study Completion: October 28, 2020
• Last Updated: November 18, 2021
• Results First Posted: November 18, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)