A Phase II Trial of Sofosbuvir (SOF) and GS-5816 for People With Chronic Hepatitis C Virus Infection and Recent Injection Drug Use

Phase 2

Completed

• Conditions: Hepatitis C
• Interventions: Drug: Sofosbuvir (SOF)/GS-5816

• Registration Number: NCT02336139
• Lead Sponsor: Kirby Institute

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-01-04
• Study First Submitted QC: 2015-01-07
• Study First Posted: 2015-01-12
• Study Start: 2016-03-16
• Primary Completion: 2017-04-17
• Study Completion: 2018-11-28
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-26
• Last Update Posted: 2019-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sofosbuvir (SOF)/GS-5816	Sofosbuvir (SOF)/GS-5816	12 weeks of Sofosbuvir (SOF)/GS-5816 (400mg/100mg) in an oral once-daily fixed dose combination

Primary Outcome Measures

Name	Time	Method
Sustained Virological Response (SVR12)	Week 24	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.

Secondary Outcome Measures

Name	Time	Method
Change in health related quality of life	Baseline to Week 12	To evaluate the change in health-related quality of life during treatment
Factors associated with on-treatment adherence	Baseline to Week 12	To evaluate factors associated with on-treatment adherence \>90% and treatment discontinuation. Demographic and behavioural factors will be examined.
Safety and tolerability (number and type of adverse events and serious adverse events)	Baseline to Week 24	To evaluate the number and type of adverse events and serious adverse events on treament and for 12 weeks post end of treatment
Change in drug use	Baseline to Week 12	To evaluate the change in drug use during treatment
Impact of mixed infection on treatment response	Baseline to Week 24	To evaluate the rate of mixed HCV infection at baseline and among those with treatment non-response
Utility of Dried Blood Spot (DBS) (method for monitoring HCV including treatment response)	Week 108	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)
Treatment adherence	Baseline to Week 12	To evaluate the proportion of patients adherent to therapy (both on-treatment adherence and treatment discontinuation)
Impact of adherence on therapy (association between adherence and response to treatment )	early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) during therapy	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.
End of Treatment Response (ETR) (proportion of participants with undetectable HCV RNA at the end of treatment (ETR)	Week 12	To evaluate the proportion of participants with undetectable HCV RNA at the end of treatment (ETR)
Reinfection Rate	Week 108	To evaluate the rate of HCV reinfection during and up to two years following treatment
Immunovirological factors associated with treatment clearance	Week 24	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
Change in mental health	Basleine to Week 12	To evaluate the change in mental health during treatment

Trial Locations

Locations (1)

The Kirby Institute; 🇦🇺 Sydney, New South Wales, Australia