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

Kirby Institute

Status and phase: Completed; Phase 2

Conditions: Hepatitis C

Treatments: Drug: Sofosbuvir (SOF)/GS-5816

Study type: Interventional

Funder types: Other

Identifiers

NCT02336139

VHCRP1309

Details and patient eligibility

About

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.

Enrollment: 103 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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103 participants in 1 patient group

Sofosbuvir (SOF)/GS-5816

Experimental group

Description:

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

Treatment:

Drug: Sofosbuvir (SOF)/GS-5816