Clinical trial NCT02940691: Scale-up of Treatment of Hepatitis C Infection Among People Who Inject Drugs
Official title: A Phase IV, Open-label, Single Arm, Multicentre Trial of Grazoprevir/Elbasvir for Genotype 1 or 4 in People With Chronic Hepatitis C Virus Infection and Recent Injecting Drug Use or Receiving Opioid Substitution Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hepatitis C
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
First posted: 2016-10-21
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a phase IV, open-label, single arm, multicentre study whose aim is to assess whether interferon-free and ribavirin-free Direct Acting Antiviral (DAA) Hepatitis C Virus (HCV) therapy with grazoprevir/elbasvir, will be feasible for the treatment of People who inject drugs (PWID) with recent injecting drug use or people receiving opioid substitution therapy and chronic HCV genotype 1 or 4 infection.

Detailed description: A prospective, observational cohort design will be used to enrol patients attending tertiary, drug and alcohol and primary health care services in Sydney, Australia.

The study consists of a treatment phase (12 weeks) and a follow-up phase (up to 3 years) where participants will be followed every 3 months for the first year and every 6 months in years 2-3 to evaluate treatment response and reinfection.

The effectiveness of the treatment will be assessed by looking at the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following therapy with grazoprevir/elbasvir and evaluate demographic and clinical predictors of non-response.

Eligibility criteria: Inclusion Criteria:

* Participants have voluntarily signed the informed consent form.
* Be ≥18 years of age on day of signing informed consent form.
* Have chronic HCV genotype 1 or 4 infection (defined as detectable HCV RNA).
* Recent injecting drug use (previous 6 months) or receiving opioid substitution therapy.
* HIV-1 infected subjects enrolled in the study must meet the following criteria:

  * Have HIV infection documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry (Baseline) and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load
  * b) Be on HIV Antiretroviral Therapy (ART) for at least 4 weeks prior to study entry using an ART regimen that is allowable with the intended DAA regimen as determined by the current PI and the Liverpool drug interaction website (http://www.hiv-druginteractions.org/) or current prescribing guidelines for elbasvir/grazoprevir OR be naive to treatment with any antiretroviral therapy (ART) with a baseline CD4 count of \>200 and have no plans to initiate ART treatment while participating in this study and through to at least Follow-up Week 4.
* Negative pregnancy test at screening and baseline (females of childbearing potential only).
* All fertile males and females must be using effective contraception during treatment and during 14 days after treatment end.

Exclusion Criteria:

* Is taking or plans to take any prohibited medications as per DAA Product Information or herbal supplements, including but not limited to St. John's Wort (Hypericum perforatum) within 2 weeks of Baseline.
* Is currently using or intends to use barbiturates.
* Is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from Baseline and continue throughout treatment, and after the last dose of study medication (as per the regimen requirements), or longer if dictated by local regulations.
* Has any condition or pre-study laboratory abnormality, ECG abnormality or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the subject.
* Had a life-threatening SAE during the screening period.
* Has exclusionary laboratory values as listed below:

  * Haemoglobin \< 9.5 g/dL for both males and females
  * Platelets \< 50 x 10\^3 /µL
  * Serum albumin \< 3.0 g/dL
* Patients with Child Pugh-B or C decompensated cirrhosis
* Previous HCV treatment-experience.
* Ongoing severe psychiatric disease as judged by the treating physician.
* Frequent injecting drug use that is judged by the treating physician to compromise treatment safety.
* Inability or unwillingness to provide informed consent or abide by the requirements of the study.
* Is Hepatitis B surface antigen (HBsAg) positive

NOTE: Sanger sequencing will be performed on a pre-treatment sample on all participants.

Primary outcomes:
measure: Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12)
timeFrame: 12 weeks post treatment
Secondary outcomes:
measure: Number of Participants With Treatment Completion
timeFrame: 12 weeks from treatment administration
measure: End of Treatment Response (Negative HCV RNA at the End of Treatment)
timeFrame: 12 weeks from treatment administration
Other outcomes:
measure: Sensitivity and Specificity of the Finger-stick Xpert® HCV Viral Load Assay for HCV RNA Detection
timeFrame: 12 week post treatment
Locations:
city: Darlinghurst
country: Australia
facility: Kirketon Road Centre
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: The Langton Centre
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Drug and Alcohol Clinical Services (Hunter)
state: New South Wales
Study officials:
affiliation: Kirby Institute
name: Greg Dore, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grebely J, Read P, Cunningham EB, Weltman M, Matthews GV, Dunlop A, Montebello M, Martinello M, Gilliver R, Marks P, Applegate TL, Dore GJ; DARLO-C Study Group. Elbasvir and grazoprevir for hepatitis C virus genotype 1 infection in people with recent injecting drug use (DARLO-C): An open-label, single-arm, phase 4, multicentre trial. Health Sci Rep. 2020 Mar 15;3(2):e151. doi: 10.1002/hsr2.151. eCollection 2020 Jun.