Clinical trial NCT02336139: A Phase II Trial of Sofosbuvir (SOF) and GS-5816 for People With Chronic Hepatitis C Virus Infection and Recent Injection Drug Use
Official title: A Phase II, Open-label, Single Arm, Multicentre, International Trial of Sofosbuvir (SOF) and GS-5816 for People With Chronic Hepatitis C Virus Infection and Recent Injection Drug Use
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
First posted: 2015-01-12
Enrollment: 103
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: 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.


Eligibility criteria: Inclusion Criteria:

1. Participants have voluntarily signed the informed consent form.
2. 18 years of age or older.
3. Chronic HCV infection as defined by anti-HCV antibody or HCV RNA detection for greater than 6 months.
4. HCV RNA plasma ≥ 1000 IU/ml at Screening.
5. HCV genotypes 1-6.
6. Recent injecting drug use (previous 6 months).
7. Compensated liver disease.
8. Participants with Fibroscan \>12 KPa or AFP \>50 ng/mL must have an abdominal ultrasound or CT scan without evidence of hepatocellular carcinoma within 2 months prior to screening.
9. Negative pregnancy test at baseline (females of childbearing potential only).
10. All fertile males and females must be using effective contraception during treatment and during the 30 days after treatment end.

Exclusion Criteria:

1. History of any of the following:

   1. Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded.
   2. Clinical hepatic decompensation (i.e. ascites, encephalopathy or variceal haemorrhage)
   3. Solid organ transplant
   4. Malignancy within 5 years prior to screening, with exception of specific cancers that may have been cured by surgical resection (basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are also excluded.
   5. Significant drug allergy (such as anaphylaxis or hepatotoxicity).
2. Screening ECG with clinically significant abnormalities
3. Any of the following lab parameters at screening:

   1. ALT \> 10 x ULN
   2. AST \> 10 x ULN
   3. Direct bilirubin \> 1.5 x ULN
   4. Platelets \< 50,0000/μL
   5. HbA1c \> 8.5%
   6. Creatinine clearance (CLcr) \< 60 mL/min
   7. Haemoglobin \< 11 g/dL for females ; \< 12 g/dL for males
   8. Albumin \< 30g/L
   9. INR \> 1.5 ULN unless subject has known haemophilia or is stable on an anticoagulant regimen affecting INR
4. Pregnant or nursing female.
5. HIV infection or HBV infection (HBcAb and HBsAg positive)
6. Use of prohibited concomitant medications as described in section 5.2
7. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent \> 10 mg/day)
8. Known hypersensitivity to GS-5816, sofosbuvir (SOF) or formulation excipients.
9. 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.
10. Any investigational drug ≤6 weeks prior to the first dose of study drug.
11. Previous therapy with sofosbuvir (SOF) or an NS5A inhibitor prior to the first dose of study drug.
12. Ongoing severe psychiatric disease as judged by the treating physician.
13. Frequent injecting drug use that is judged by the treating physician to compromise treatment safety.
14. Inability or unwillingness to provide informed consent or abide by the requirements of the study.

Primary outcomes:
measure: Sustained Virological Response (SVR12)
timeFrame: Week 24
Secondary outcomes:
measure: Treatment adherence
timeFrame: Baseline to Week 12
measure: Impact of adherence on therapy (association between adherence and response to treatment )
timeFrame: early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) during therapy
measure: Factors associated with on-treatment adherence
timeFrame: Baseline to Week 12
measure: End of Treatment Response (ETR) (proportion of participants with undetectable HCV RNA at the end of treatment (ETR)
timeFrame: Week 12
measure: Safety and tolerability (number and type of adverse events and serious adverse events)
timeFrame: Baseline to Week 24
measure: Change in drug use
timeFrame: Baseline to Week 12
measure: Change in mental health
timeFrame: Basleine to Week 12
measure: Change in health related quality of life
timeFrame: Baseline to Week 12
measure: Impact of mixed infection on treatment response
timeFrame: Baseline to Week 24
measure: Reinfection Rate
timeFrame: Week 108
measure: Immunovirological factors associated with treatment clearance
timeFrame: Week 24
measure: Utility of Dried Blood Spot (DBS) (method for monitoring HCV including treatment response)
timeFrame: Week 108
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: The Kirby Institute
state: New South Wales
Study officials:
affiliation: Kirby Institute
name: Greg Dore, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.