None listed
Conditions
Brief summary
The study aims to evaulate the effectiveness, safety and tolerability (side effects) of GS-9620 in patients with chronic hepatitis B (CHB) who are currently being treated with oral antiviral (OAV) medication. Approximately 150 patients with CHB that are currently being treated and who have completely suppressed HBV infection, will be given an extra treatment of either GS-9620 or a dummy drug (placebo). The study aims to look at how effective GS-9620 is in combination with the already used OAV, in reducing the amount of virus in participants blood. Participants will be followed up to Week 48. The total study duration for each participant may be up to 57 weeks, inclusive of the screening, treatment and follow-up period.
Interventions
Arm 1: OAV + 1mg GS-9620
Arm 2: OAV + 2mg GS-9620
Arm 3: OAV + 4mg GS-9620
Arm 4: OAV + Placebo
OAV = Oral Antiviral (must be commercially available)
OAV type, dose and duration will continue as previously prescribed by the patient’s clinician.
For all Arms (1, 2, 3 and 4) GS-9620/placebo will be taken once a week (every 7th day) as an oral tablet.
Participants will be randomised into 3 sequential cohorts:
- Cohort A participants will be treated with GS-9620 (1mg, 2mg or 4mg)/placebo once a
Arm 1: OAV + 1mg GS-9620 Arm 2: OAV + 2mg GS-9620 Arm 3: OAV + 4mg GS-9620 Arm 4: OAV + Placebo OAV = Oral Antiviral (must be commercially available) OAV type, dose and duration will continue as previously prescribed by the patient’s clinician. For all Arms (1, 2, 3 and 4) GS-9620/placebo will be taken once a week (every 7th day) as an oral tablet. Participants will be randomised into 3 sequential cohorts: - Cohort A participants will be treated with GS-9620 (1mg, 2mg or 4mg)/placebo once a week for 4 doses - Cohort B participants will be treated with GS-9620 (1mg, 2mg or 4mg)/placebo once a week for 8 doses - Cohort C participants will be treated with GS-9620 (1mg, 2mg or 4mg)/placebo once a week for 12 doses All unused study drug and used study drug kits which are dispensed to participants must be returned to the investigative site for accountability.
Sponsors
Gilead Sciences, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following inclusion criteria to be eligible to participate in the study. 1. Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures 2. Adult male and non-pregnant, non-lactating female subjects, (lactating females must agree to discontinue nursing before the study drug is administered), 18–65 years of age inclusive based on the date of the screening visit 3. A negative serum pregnancy test is required for female subjects (unless surgically sterile or greater than two years post-menopausal). 4. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception. 5. Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months) with detectable HBsAg levels at screening 6. Have been on approved HBV OAV treatment for greater than or equal to 1 year prior to screening, with HBV DNA below LLOQ (measured at least once) 6 or more months prior to screening, and HBV DNA < 20 IU/ml at screening 7. Subjects currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening 8. Willing to provide blood sample for TLR-7 and IL28B SNP assessment 9. Must be willing and able to comply with all study requirements
Exclusion criteria
Patients who meet any of the following exclusion criteria are not to be enrolled in the study: 1. Extensive bridging fibrosis or cirrhosis as defined clinically, by imaging or by the following: a) Metavir greater than or equal to 3 or Ishak fibrosis score greater than or equal to 4 by a liver biopsy within 5 years of screening. or, in the absence of an appropriate liver biopsy, either b) Screening FibroTest score of > 0.48 and APRI > 1, or c) Historic FibroScan with a result > 9 kPa within less than than or equal to 6 months of screening (if available) If liver biopsy is available, the liver biopsy result supersedes (b) and/or (c, if available). If an appropriate liver biopsy is not available, fibrosis will be evaluated by (b) and/or (c, if available). In the event of discordance between (b) and (c), the FibroScan results will take precedence. 2. Patients meeting any of the following laboratory parameters at screening: - White Blood cell count < 2500 IU/Ml - Neutrophil count < 1500 cell/ mm3 (or < 1000 cell/ mm3 if considered a physiological variant in a subject of African descent) - ALT > 3x the upper limit of normal (ULN) - INR > ULN unless the subject is stable on an anticoagulant regimen affecting INR - Albumin < 3.9 g/dL - Total bilirubin > 2 mg/dl - Platelet Count < 125,000 /ml - Estimate creatinine clearance (CLcr) < 50 ml/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation 3. Co-infection with HCV, HIV or HDV 4. Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging) 5. Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (e.g. basal cell skin cancer). Subjects under evaluation for possible malignancy are not eligible 6. Significant cardiovascular, pulmonary, or neurological disease 7. Any of the following conditions that may worsen in response to IFN: - Autoimmune disease (e.g. lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis) - Poorly controlled diabetes mellitus - Significant psychiatric disorders - Thyroid disorder (unless controlled under treatment) - Significant pulmonary diseases (e.g. chronic obstructive pulmonary disease) - Retinal disease - Immunodeficiency disorders 8. Chronic liver disease of a non-HBV etiology (e.g. hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cholangitis) 9. Received solid organ or bone marrow transplant 10. Received prolonged therapy with immunomodulators (e.g. corticosteroids) or biologics (e.g. monoclonal Ab, interferon) within 3 months of screening 11. Use of another investigational agents within 3 months of screening, unless allowed by the Sponsor 12. Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance 13. Known hypersensitivity to study drug, metabolites or formulation excipients 14. Screening electrocardiogram (ECG) with clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia’s formula) greater than or equal to 450 msec for males and greater than or equal to 470 msec for females 15. Women who may wish to become pregnant during the course of the study 16. Male subjects unwilling to refrain from sperm donation for at least 90 days after the last dose of study drug 17. Use of any prohibited con-medications as described in the protocol 18. Believed by the Study Investigator to be inappropriate for study participation for any reason not otherwise listed
Outcome results
None listed