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To evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following sofosbuvir/GS-5816 therapy for 12 weeks in people with chronic HCV infection and recent injection drug use.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sofosbuvir (SOF)/GS-5816 | Experimental | 12 weeks of Sofosbuvir (SOF)/GS-5816 (400mg/100mg) in an oral once-daily fixed dose combination |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sofosbuvir (SOF)/GS-5816 | Drug | 12 weeks of Sofosbuvir (SOF)/GS-5816 (400mg/100mg) in an oral once-daily fixed dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Sustained Virological Response (SVR12) | To evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following sofosbuvir (SOF)/GS-5816 therapy for 12 weeks in people with chronic HCV infection and recent injection drug use. | Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment adherence | To evaluate the proportion of patients adherent to therapy (both on-treatment adherence and treatment discontinuation) | Baseline to Week 12 |
| Impact of adherence on therapy (association between adherence and response to treatment ) |
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Inclusion Criteria:
Exclusion Criteria:
History of any of the following:
Screening ECG with clinically significant abnormalities
Any of the following lab parameters at screening:
Pregnant or nursing female.
HIV infection or HBV infection (HBcAb and HBsAg positive)
Use of prohibited concomitant medications as described in section 5.2
Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day)
Known hypersensitivity to GS-5816, sofosbuvir (SOF) or formulation excipients.
Therapy with any anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of study drug.
Any investigational drug ≤6 weeks prior to the first dose of study drug.
Previous therapy with sofosbuvir (SOF) or an NS5A inhibitor prior to the first dose of study drug.
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.
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| Name | Affiliation | Role |
|---|---|---|
| Greg Dore, MBBS PhD | Kirby Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Kirby Institute | Sydney | New South Wales | 2052 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32166305 | Derived | Cunningham EB, Hajarizadeh B, Amin J, Hellard M, Bruneau J, Feld JJ, Cooper C, Powis J, Litwin AH, Marks P, Dalgard O, Conway B, Moriggia A, Stedman C, Read P, Bruggmann P, Lacombe K, Dunlop A, Applegate TL, Matthews GV, Fraser C, Dore GJ, Grebely J. Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs. Clin Infect Dis. 2021 Apr 26;72(8):1392-1400. doi: 10.1093/cid/ciaa253. | |
| 31300820 |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| D000069474 | Sofosbuvir |
| ID | Term |
|---|---|
| D014542 | Uridine Monophosphate |
| D014500 | Uracil Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
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To evaluate the association between adherence and response to treatment [including an evaluation of the impact of early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) missed doses on response to therapy]; Adehernce will be measure via a self report quesitonanire and pill counts via return of the weeekly blister packs. The impact of the number and timing of missed pills will be evaluated. |
| early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) during therapy |
| Factors associated with on-treatment adherence | To evaluate factors associated with on-treatment adherence >90% and treatment discontinuation. Demographic and behavioural factors will be examined. | Baseline to Week 12 |
| End of Treatment Response (ETR) (proportion of participants with undetectable HCV RNA at the end of treatment (ETR) | To evaluate the proportion of participants with undetectable HCV RNA at the end of treatment (ETR) | Week 12 |
| Safety and tolerability (number and type of adverse events and serious adverse events) | To evaluate the number and type of adverse events and serious adverse events on treament and for 12 weeks post end of treatment | Baseline to Week 24 |
| Change in drug use | To evaluate the change in drug use during treatment | Baseline to Week 12 |
| Change in mental health | To evaluate the change in mental health during treatment | Basleine to Week 12 |
| Change in health related quality of life | To evaluate the change in health-related quality of life during treatment | Baseline to Week 12 |
| Impact of mixed infection on treatment response | To evaluate the rate of mixed HCV infection at baseline and among those with treatment non-response | Baseline to Week 24 |
| Reinfection Rate | To evaluate the rate of HCV reinfection during and up to two years following treatment | Week 108 |
| Immunovirological factors associated with treatment clearance | To evaluate immunovirological factors associated with treatment clearance. We will evaluate cytokines and chemokines (e.g. interferon inducible protein 10), T-cell responses, viral evolution and genetic markers (e.g. inteferon lambda 4) that are potentially associated with treatment induced clearance | Week 24 |
| Utility of Dried Blood Spot (DBS) (method for monitoring HCV including treatment response) | To evaluate the utility of dried blood spot (DBS) as a simple method for monitoring HCV including treatment response. HCV RNA will be measured from DBS samples and then compared to HCV RNA levels measured using standard methods (EDTA Plasma samples and Roche Taqman) | Week 108 |
| Derived |
| Artenie AA, Cunningham EB, Dore GJ, Conway B, Dalgard O, Powis J, Bruggmann P, Hellard M, Cooper C, Read P, Feld JJ, Hajarizadeh B, Amin J, Lacombe K, Stedman C, Litwin AH, Marks P, Matthews GV, Quiene S, Erratt A, Bruneau J, Grebely J. Patterns of Drug and Alcohol Use and Injection Equipment Sharing Among People With Recent Injecting Drug Use or Receiving Opioid Agonist Treatment During and Following Hepatitis C Virus Treatment With Direct-acting Antiviral Therapies: An International Study. Clin Infect Dis. 2020 May 23;70(11):2369-2376. doi: 10.1093/cid/ciz633. |
| 29310928 | Derived | Grebely J, Dalgard O, Conway B, Cunningham EB, Bruggmann P, Hajarizadeh B, Amin J, Bruneau J, Hellard M, Litwin AH, Marks P, Quiene S, Siriragavan S, Applegate TL, Swan T, Byrne J, Lacalamita M, Dunlop A, Matthews GV, Powis J, Shaw D, Thurnheer MC, Weltman M, Kronborg I, Cooper C, Feld JJ, Fraser C, Dillon JF, Read P, Gane E, Dore GJ; SIMPLIFY Study Group. Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Lancet Gastroenterol Hepatol. 2018 Mar;3(3):153-161. doi: 10.1016/S2468-1253(17)30404-1. Epub 2018 Jan 6. |
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |