Clinical Trials List
Protocol NumberGS-US-389-2025
NCT Number(ClinicalTrials.gov Identfier)NCT03615066
2018-08-28 - 2021-04-12
Phase II
Terminated3
ICD-10B18.1
Chronic viral hepatitis B without delta-agent
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Viremic Adult Subjects with Chronic Hepatitis B who are not currently on Treatment
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Trial Applicant
GILEAD SCIENCES HONG KONG LIMITED
-
Sponsor
Gilead Sciences
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 曾岱宗 無
- Chun-Jen Liu 無
- 王一中 無
- 楊宏志 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 徐旭亮 無
- Ming-Lun Yeh 無
- 黃駿逸 無
- Jee-Fu Huang 無
- Chia-Yen Dai 無
- Ming-Lung Yu 無
- Chung-Feng Huang 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Viremic Chronic Hepatitis B
Objectives
The primary objectives of this study are as follows:
To evaluate the safety and tolerability of multiple oral doses of
GS-9688 at Week 24 in chronic hepatitis B (CHB) adult subjects
who are viremic and not currently not being treated
To evaluate the antiviral activity of GS-9688 as measured by the
proportion of subjects with ≥1 log10 IU/mL decline from baseline
in serum quantitative hepatitis B surface antigen (qHBsAg) at
Week 24
The secondary objectives of this study are as follows:
To evaluate the antiviral activity of GS-9688 at Weeks 4, 8,
12 and 48 as measured by the proportion of subjects with
≥1 log10 IU/mL decline from baseline in serum qHBsAg
To evaluate the change in serum qHBsAg (log10 IU/mL) from
baseline to Weeks 4, 8, 12, 24 and 48
To evaluate the proportion of subjects with HBV DNA <LLOQ
at Weeks 12, 24, and 48
To evaluate the proportion of subjects with HBsAg loss at
Weeks 12, 24 and 48
To evaluate the proportion of subjects with Hepatitis B e-Antigen
(HBeAg) loss and seroconversion at Weeks 12, 24 and 48
To characterize the pharmacokinetics (PK) of GS-9688
To evaluate the proportion of subjects experiencing Hepatitis B
virus (HBV) virologic breakthrough (2 consecutive visits of
HBV DNA ≥ 69 IU/mL)
To evaluate the incidence of drug resistance mutations
The exploratory objectives of this study are as follows:
To evaluate the effect of GS-9688 on pharmacodynamic (PD) markers
To evaluate the antiviral activity of GS-9688 at Weeks 12, 24,
and 48 as measured by the change from baseline in quantitative
HBeAg, HBV Ribonucleic acid (RNA), and hepatitis B
core-related antigen (HBcrAg)
To evaluate the association between alanine aminotransferase
(ALT) flares (defined as ALT > 2x BL and ≥5x the upper limit
of normal [ULN]) and qHBsAg decline
To characterize the relationship between the PK and/or PD of
GS-9688 and viral parameters
To characterize the relationship of ex vivo Truculture findings
with the biological activity of GS-9688 as measured by changes
in PD markers and viral parameters
To characterize immunologic changes with GS-9688 treatment
To evaluate the association of single-nucleotide polymorphisms
(SNPs) with PD response and change in HBsAg levels
To evaluate the effects of GS-9688 on the microbiome
To assess the effect of treatment on Health Related Quality of Life (HRQoL)
Test Drug
GS-9688 Film-coated Tablets, 1.5mg
Active Ingredient
GS-9688
Dosage Form
Film-coated Tablets
Dosage
1.5
Endpoints
The primary efficacy endpoint is:
Proportion of subjects with ≥ 1 log10 IU/mL decline in serum
qHBsAg from baseline at Week 24
The secondary efficacy endpoints are:
Proportion of subjects with ≥ 1 log10 IU/mL decline in serum
qHBsAg from baseline at Weeks 4, 8, 12 and 48
Change in serum qHBsAg (log10 IU/mL) from baseline at
Weeks 4, 8, 12, 24 and 48
To evaluate the proportion of subjects with HBV DNA
Proportion of subjects with HBsAg loss at Weeks 12, 24 and 48
Proportion of subjects with HBeAg loss and seroconversion at
Weeks 12, 24 and 48
Proportion of subjects with virologic breakthrough
(2 consecutive visits of HBV DNA ≥ 69 IU/mL)
Proportion of subjects with drug resistance mutations
Proportion of subjects with ≥ 1 log10 IU/mL decline in serum
qHBsAg from baseline at Week 24
The secondary efficacy endpoints are:
Proportion of subjects with ≥ 1 log10 IU/mL decline in serum
qHBsAg from baseline at Weeks 4, 8, 12 and 48
Change in serum qHBsAg (log10 IU/mL) from baseline at
Weeks 4, 8, 12, 24 and 48
To evaluate the proportion of subjects with HBV DNA
Proportion of subjects with HBsAg loss at Weeks 12, 24 and 48
Proportion of subjects with HBeAg loss and seroconversion at
Weeks 12, 24 and 48
Proportion of subjects with virologic breakthrough
(2 consecutive visits of HBV DNA ≥ 69 IU/mL)
Proportion of subjects with drug resistance mutations
Inclution 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,
18-65 years of age inclusive based on the date of the Screening visit.
3) Documented evidence of chronic HBV infection
(e.g., HBsAg positive for more than 6 months) with detectable
HBsAg levels at Screening.
4) Females of childbearing potential (as defined in Appendix 3)
must have a negative serum pregnancy test at Screening and a
negative urine pregnancy test at Baseline prior to enrollment.
5) Male and female subjects of childbearing potential who engage
in heterosexual intercourse must agree to use protocol specified
method(s) of contraception as described in Appendix 3
6) Screening HBV Deoxyribonucleic acid (DNA) ≥ 2000 IU/mL.
7) Screening Electrocardiogram (ECG) without clinically
significant abnormalities and with QTcF interval (QT corrected
using Fridericia’s formula) ≤ 450 msec for males and ≤ 470 msec for females.
8) Must be willing and able to comply with all study requirements.
consent form, which must be obtained prior to initiation of study
procedures.
2) Adult male and non-pregnant, non-lactating female subjects,
18-65 years of age inclusive based on the date of the Screening visit.
3) Documented evidence of chronic HBV infection
(e.g., HBsAg positive for more than 6 months) with detectable
HBsAg levels at Screening.
4) Females of childbearing potential (as defined in Appendix 3)
must have a negative serum pregnancy test at Screening and a
negative urine pregnancy test at Baseline prior to enrollment.
5) Male and female subjects of childbearing potential who engage
in heterosexual intercourse must agree to use protocol specified
method(s) of contraception as described in Appendix 3
6) Screening HBV Deoxyribonucleic acid (DNA) ≥ 2000 IU/mL.
7) Screening Electrocardiogram (ECG) without clinically
significant abnormalities and with QTcF interval (QT corrected
using Fridericia’s formula) ≤ 450 msec for males and ≤ 470 msec for females.
8) 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 3 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) Received a commercially available HBV OAV treatment(s)
(tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir,
adefovir dipivoxil, lamivudine, telbivudine, either as single
agents or in combination) within the 3 months prior to screening.
3) Received prolonged therapy with immunomodulators
(e.g., corticosteroids) or biologics (e.g., monoclonal antibody,
interferon) within 3 months of screening
4) Subjects meeting any of the following laboratory parameters at
screening:
a) Hemoglobin < 12 g/dL (for males) or <11 g/dL (for females)
b) White Blood cell count < 2500 cells/mm3
c) Neutrophil count < 1500 cells/mm3
(or < 1000 cells/mm3
if
considered a physiological variant in a subject of African
descent)
d) Alanine aminotransferase (ALT) >5x ULN
e) International normalized ratio (INR) > ULN unless the
subject is stable on an anticoagulant regimen affecting INR
f) Albumin < 3.5 g/dL
g) Direct bilirubin >1.5x ULN
h) Platelet Count < 100,000/L
i) Estimated creatinine clearance (CrCl) < 60 mL/min (using the
Cockcroft-Gault method) based on serum creatinine and actual
body weight as measured at the screening evaluation, i.e.,
Male: (140 – Age [years]) (Weight [kg]) CrCl (mL/min)
72 (Serum Creatinine [mg/dL])
Female: (140 – Age [years]) (Weight [kg]) 0.85CrCl (mL/min)
72 (Serum Creatinine [mg/dL])
5) Co-infection with human immunodeficiency virus (HIV),
hepatitis C virus (HCV) or hepatitis D virus (HDV)
Subjects who are HCV Ab positive, but have a documented
negative HCV RNA, are eligible
6) Prior history of hepatocellular carcinoma (HCC)
(e.g., as evidenced by prior imaging) or screening
alpha-fetoprotein (AFP) ≥ 50 ng/mL without imaging to rule out
HCC.
7) 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.
8) Significant cardiovascular, pulmonary, or neurological disease in
the opinion of the investigator.
9) Diagnosis of autoimmune disease (e.g., systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel
disease, autoimmune hepatitis, sarcoidosis, psoriasis of greater
than mild severity, autoimmune uveitis), poorly controlled
diabetes mellitus, significant psychiatric illness, severe chronic
obstructive pulmonary disease (COPD), hemoglobinopathy,
retinal disease, or are immunosuppressed.
10) Chronic liver disease of a non-HBV etiology
(e.g., Wilson’s disease, hemochromatosis, alpha-1-antitrypsin
deficiency, cholangitis, nonalcoholic steatohepatitis), except for
non-alcoholic fatty liver disease.
11) Received solid organ or bone marrow transplant.
12) Use of another investigational agent within 90 days of screening,
unless allowed by the Sponsor.
13) Current alcohol or substance abuse judged by the investigator to
potentially interfere with subject compliance.
14) Known hypersensitivity to study drugs or formulation excipients.
15) Women who are breastfeeding, pregnant or who wish to become
pregnant during the course of the study.
16) Female subjects unwilling to refrain from egg donation and in
vitro fertilization during and until at least 30 days after the last
study drug dose.
17) Male subjects unwilling to refrain from sperm donation during
and until at least 90 days after the last study drug dose.
18) Use of any prohibited concomitant medications as described in
Section 5.5 and Table 5-1.
19) Believed by the Study Investigator to be inappropriate for study
participation for any reason not otherwise listed.
imaging or by the following:
a) Metavir ≥ 3 or Ishak fibrosis score ≥ 4 by a liver biopsy
within 3 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) Received a commercially available HBV OAV treatment(s)
(tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir,
adefovir dipivoxil, lamivudine, telbivudine, either as single
agents or in combination) within the 3 months prior to screening.
3) Received prolonged therapy with immunomodulators
(e.g., corticosteroids) or biologics (e.g., monoclonal antibody,
interferon) within 3 months of screening
4) Subjects meeting any of the following laboratory parameters at
screening:
a) Hemoglobin < 12 g/dL (for males) or <11 g/dL (for females)
b) White Blood cell count < 2500 cells/mm3
c) Neutrophil count < 1500 cells/mm3
(or < 1000 cells/mm3
if
considered a physiological variant in a subject of African
descent)
d) Alanine aminotransferase (ALT) >5x ULN
e) International normalized ratio (INR) > ULN unless the
subject is stable on an anticoagulant regimen affecting INR
f) Albumin < 3.5 g/dL
g) Direct bilirubin >1.5x ULN
h) Platelet Count < 100,000/L
i) Estimated creatinine clearance (CrCl) < 60 mL/min (using the
Cockcroft-Gault method) based on serum creatinine and actual
body weight as measured at the screening evaluation, i.e.,
Male: (140 – Age [years]) (Weight [kg]) CrCl (mL/min)
72 (Serum Creatinine [mg/dL])
Female: (140 – Age [years]) (Weight [kg]) 0.85CrCl (mL/min)
72 (Serum Creatinine [mg/dL])
5) Co-infection with human immunodeficiency virus (HIV),
hepatitis C virus (HCV) or hepatitis D virus (HDV)
Subjects who are HCV Ab positive, but have a documented
negative HCV RNA, are eligible
6) Prior history of hepatocellular carcinoma (HCC)
(e.g., as evidenced by prior imaging) or screening
alpha-fetoprotein (AFP) ≥ 50 ng/mL without imaging to rule out
HCC.
7) 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.
8) Significant cardiovascular, pulmonary, or neurological disease in
the opinion of the investigator.
9) Diagnosis of autoimmune disease (e.g., systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel
disease, autoimmune hepatitis, sarcoidosis, psoriasis of greater
than mild severity, autoimmune uveitis), poorly controlled
diabetes mellitus, significant psychiatric illness, severe chronic
obstructive pulmonary disease (COPD), hemoglobinopathy,
retinal disease, or are immunosuppressed.
10) Chronic liver disease of a non-HBV etiology
(e.g., Wilson’s disease, hemochromatosis, alpha-1-antitrypsin
deficiency, cholangitis, nonalcoholic steatohepatitis), except for
non-alcoholic fatty liver disease.
11) Received solid organ or bone marrow transplant.
12) Use of another investigational agent within 90 days of screening,
unless allowed by the Sponsor.
13) Current alcohol or substance abuse judged by the investigator to
potentially interfere with subject compliance.
14) Known hypersensitivity to study drugs or formulation excipients.
15) Women who are breastfeeding, pregnant or who wish to become
pregnant during the course of the study.
16) Female subjects unwilling to refrain from egg donation and in
vitro fertilization during and until at least 30 days after the last
study drug dose.
17) Male subjects unwilling to refrain from sperm donation during
and until at least 90 days after the last study drug dose.
18) Use of any prohibited concomitant medications as described in
Section 5.5 and Table 5-1.
19) Believed by the Study Investigator to be inappropriate for study
participation for any reason not otherwise listed.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
65 participants
