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

Hepatitis C Clinical Trial

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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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02336139
• Other study ID #: VHCRP1309
• Status: Completed
• Phase: Phase 2
• Start date: March 16, 2016
• Est. completion date: November 28, 2018

Study information

• Verified date: February 2019
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: November 28, 2018
• Est. primary completion date: April 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Virus Diseases

Intervention

Drug:
• Sofosbuvir (SOF)/GS-5816
12 weeks of Sofosbuvir (SOF)/GS-5816 (400mg/100mg) in an oral once-daily fixed dose

Locations

Country	Name	City	State
Australia	The Kirby Institute	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Kirby Institute

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Treatment adherence	To evaluate the proportion of patients adherent to therapy (both on-treatment adherence and treatment discontinuation)	Baseline to Week 12
Secondary	Impact of adherence on therapy (association between adherence and response to treatment )	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in drug use	To evaluate the change in drug use during treatment	Baseline to Week 12
Secondary	Change in mental health	To evaluate the change in mental health during treatment	Basleine to Week 12
Secondary	Change in health related quality of life	To evaluate the change in health-related quality of life during treatment	Baseline to Week 12
Secondary	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
Secondary	Reinfection Rate	To evaluate the rate of HCV reinfection during and up to two years following treatment	Week 108
Secondary	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
Secondary	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