A Phase 1b Study Evaluating the Safety and Tolerability of GS-5801 in Patients with Chronic Hepatitis B

Phase 1

Terminated

• Conditions: Chronic Hepatitis B; Infection - Other infectious diseases

• Registration Number: ACTRN12616001375448
• Lead Sponsor: Gilead Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-10-05
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Must have the ability to understand and sign a written informed consent form, which 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 and through the follow up period), 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 postmenopausal).
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 =>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 Tenofovir DF, Tenofovir alafenamide, entecavir, adefovir, lamivudine, or telbivudine, either as single agent or in combination with no change in regimen for 3 months prior to screening.
8. Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia’s formula) =<450 msec for males and =<470 msec for females
9. Body mass index (BMI) 18-34 kg/m2, inclusive
10. Must be willing and able to comply with all study requirements

Exclusion Criteria

1. Extensive bridging fibrosis or cirrhosis as defined clinically, by imaging or by the following:
a. Metavir => 3 or Ishak fibrosis score => 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 =< 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. Subjects meeting any of the following laboratory parameters at Screening:
a. Hemoglobin <12 g/dL (for males), <11 g/dL (for females)
b. White Blood cell count < 2500 IU/mL
c. ALT > 3x ULN
d. Direct bilirubin > 1.5x ULN
e. INR > ULN unless the subject is stable on an anticoagulant regimen affecting INR
f. Albumin < 3.9 g/dL
g. Platelet Count < 125,000 /mL
h. Estimate creatinine clearance (CLcr) < 80 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 HIV, hepatitis C virus (HCV) or hepatitis D virus (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. Diagnosis of autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, psoriasis of greater than mild severity), poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), malignancy (with exception of certain skin cancers) hemoglobinopathy, retinal disease, or are immunosuppressed
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 antibody, interferon) within 3 months of Screening
11. Use of another investigational agents within 30 days 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. Women who may wish to become pregnant during the course of the study
15. Male subjects unwilling to refrain from sperm donation for at least 90 days after the last dose of study drug
16. Use of any prohibited concomitant -medications
17. Believed by the Study Investigator to be inappropriate for study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the safety and tolerability of multiple oral doses of GS-5801 in subjects with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV).[Safety will be evaluated throughout the study. <br>Incidences of adverse events will be monitored continuously from screening to end of study. <br>Vital signs: Screening, Day1, 2, 5, 7, 8, 14, 21, 35 and early termination<br>ECG: Screening, Day1, 2, 5 14, and early termination<br>Lab assessments: Screening, Day1, 2, 5, 7, 8, 14, 21, 35 and early termination]

Secondary Outcome Measures

Name	Time	Method
To evaluate the antiviral activity of GS-5801 measured by the change from Baseline (BL) in serum hepatitis B surface antigen (HBsAg log10 IU/mL) levels [HBsAg will be done at Screening, Day 1, 14, 35 and early termination.];To characterize the pharmacokinetics (PK) of GS-5801 and its metabolites. <br><br>Plasma PK concentrations and parameters assessed: AUClast, AUCinf, AUCtau, % AUCexp, Ctau, Tmax, Tlast, CL/F, t1/2 and Cmax, of GS-5801 and its metabolite GS-698080.[Part A and B (Cohorts 1-6): Intensive PK sampling will occur relative to dosing of GS-5801 or placebo at the following time points for each cohort:<br>Day 1: 0 (predose, =< 5 min prior to dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours postdose.<br>Days 7: 0 (predose, =< 5 min prior to dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours postdose.]