Back to resultsStudy to Evaluate the Safety, Tolerability, and Efficacy of Vesatolimod in Combination With Tenofovir Disoproxil Fumarate (TDF) in Adults With Chronic Hepatitis B (CHB) Infection Who Are Currently Not Being Treated
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TDF
Vesatolimod
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring HBV, Hepatitis, Liver Disease
Eligibility Criteria
Key Inclusion Criteria:
- Adult males or females between the ages of 18-65
- Chronic hepatitis B virus (HBV) infection
- HBV deoxyribonucleic acid (DNA ) ≥ 2000 IU/mL at screening
Key Exclusion Criteria:
- Extensive bridging fibrosis or cirrhosis
- Received oral antiviral treatment for HBV or prolonged therapy with immune-modulators or biologics within 3 months of screening
- Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV) or hepatitis D virus (HDV)
- Chronic liver disease other than HBV
- Lactating or pregnant females or those that wish to become pregnant during the course of the study
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
TDF + placebo
TDF + Vesatolimod 1 mg
TDF + Vesatolimod 2 mg
TDF + Vesatolimod 4 mg
Arm Description
Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Outcomes
Primary Outcome Measures
Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24
The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analyzed using a mixed model for repeated measures (MMRM). The model included treatment, baseline HBsAg (log10 IU/mL), baseline Hepatitis B Envelope Antigen (HBeAg) status (positive or negative), baseline alanine aminotransferase (ALT) level relative to upper limit of normal (ULN) (> 19 vs ≤ 19 IU/L for females; > 30 vs ≤ 30 IU/L for males), visit and treatment-by-visit interaction as fixed effects, and visit as a repeated measure.
Secondary Outcome Measures
Percentage of Participants With HBeAg Loss and Seroconversion at Week 24
HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative Hepatitis B Envelope Antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.
Percentage of Participants With HBeAg Loss and Seroconversion at Week 48
HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.
Percentage of Participants With HBsAg Loss and Seroconversion at Week 24
HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative Hepatitis B Surface Antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.
Percentage of Participants With HBsAg Loss and Seroconversion at Week 48
HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.
Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12
Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12
HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24
HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 24 post-baseline visit.
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48
HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.
Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24
LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.
Percentage of Participants With HBV DNA < LLOQ at Week 48
LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.
Percentage of Participants Experiencing Virologic Breakthrough
Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having had HBV DNA < 69 IU/mL or confirmed 1.0 log10 IU/mL or greater increase in HBV DNA from nadir. Confirmation requires 2 consecutive occurrences of elevation in HBV DNA to > 69 IU/mL after having had HBV DNA < 69 IU/mL or 1.0 log10 IU/mL or greater increases in HBV DNA from nadir.
Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT)
Sequence analysis of the HBV pol/RT was attempted for any participant who had HBV DNA ≥ 69 IU/mL at Week 48 or early discontinuation. Results of the alignment of Week 48 and baseline sequence were reported as a change from baseline sequence.
Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod
AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.
PK Parameter: AUCinf of Vesatolimod
AUCinf is defined as the concentration of drug extrapolated to infinite time.
PK Parameter: %AUCexp of Vesatolimod
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
PK Parameter: Cmax of Vesatolimod
Cmax is defined as the maximum concentration of drug.
PK Parameter: Clast of Vesatolimod
Clast is defined as the last observable concentration of drug.
PK Parameter: Tmax of Vesatolimod
Tmax is defined as the time (observed time point) of Cmax
PK Parameter: Tlast of Vesatolimod
Tlast is defined as the time (observed time point) of Clast.
PK Parameter: T1/2 of Vesatolimod
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: CL/F of Vesatolimod
CL/F is defined as the apparent oral clearance following administration of the drug.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02579382
Brief Title
Study to Evaluate the Safety, Tolerability, and Efficacy of Vesatolimod in Combination With Tenofovir Disoproxil Fumarate (TDF) in Adults With Chronic Hepatitis B (CHB) Infection Who Are Currently Not Being Treated
Official Title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
November 10, 2015 (Actual)
Primary Completion Date
January 16, 2017 (Actual)
Study Completion Date
May 3, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod (formerly GS-9620) in adults with chronic hepatitis B (CHB) infection who are currently not being treated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
HBV, Hepatitis, Liver Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
192 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TDF + placebo
Arm Type
Placebo Comparator
Arm Description
Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Arm Title
TDF + Vesatolimod 1 mg
Arm Type
Experimental
Arm Description
Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Arm Title
TDF + Vesatolimod 2 mg
Arm Type
Experimental
Arm Description
Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Arm Title
TDF + Vesatolimod 4 mg
Arm Type
Experimental
Arm Description
Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention Type
Drug
Intervention Name(s)
TDF
Other Intervention Name(s)
Viread®
Intervention Description
300 mg tablets administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Vesatolimod
Other Intervention Name(s)
GS-9620
Intervention Description
Tablets administered orally once a week (every 7 days) for 12 doses
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo administered orally once a week (every 7 days) for 12 doses
Primary Outcome Measure Information:
Title
Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24
Description
The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analyzed using a mixed model for repeated measures (MMRM). The model included treatment, baseline HBsAg (log10 IU/mL), baseline Hepatitis B Envelope Antigen (HBeAg) status (positive or negative), baseline alanine aminotransferase (ALT) level relative to upper limit of normal (ULN) (> 19 vs ≤ 19 IU/L for females; > 30 vs ≤ 30 IU/L for males), visit and treatment-by-visit interaction as fixed effects, and visit as a repeated measure.
Time Frame
Baseline; Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants With HBeAg Loss and Seroconversion at Week 24
Description
HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative Hepatitis B Envelope Antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.
Time Frame
Week 24
Title
Percentage of Participants With HBeAg Loss and Seroconversion at Week 48
Description
HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.
Time Frame
Week 48
Title
Percentage of Participants With HBsAg Loss and Seroconversion at Week 24
Description
HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative Hepatitis B Surface Antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.
Time Frame
Week 24
Title
Percentage of Participants With HBsAg Loss and Seroconversion at Week 48
Description
HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.
Time Frame
Week 48
Title
Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12
Time Frame
Baseline; Week 12
Title
Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48
Time Frame
Baseline; Week 48
Title
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12
Description
HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.
Time Frame
Baseline to Week 12
Title
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24
Description
HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 24 post-baseline visit.
Time Frame
Baseline to Week 24
Title
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48
Description
HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.
Time Frame
Baseline to Week 48
Title
Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24
Description
LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.
Time Frame
Week 24
Title
Percentage of Participants With HBV DNA < LLOQ at Week 48
Description
LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.
Time Frame
Week 48
Title
Percentage of Participants Experiencing Virologic Breakthrough
Description
Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having had HBV DNA < 69 IU/mL or confirmed 1.0 log10 IU/mL or greater increase in HBV DNA from nadir. Confirmation requires 2 consecutive occurrences of elevation in HBV DNA to > 69 IU/mL after having had HBV DNA < 69 IU/mL or 1.0 log10 IU/mL or greater increases in HBV DNA from nadir.
Time Frame
Weeks 24 and 48
Title
Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT)
Description
Sequence analysis of the HBV pol/RT was attempted for any participant who had HBV DNA ≥ 69 IU/mL at Week 48 or early discontinuation. Results of the alignment of Week 48 and baseline sequence were reported as a change from baseline sequence.
Time Frame
Baseline; Week 48
Title
Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod
Description
AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Title
PK Parameter: AUCinf of Vesatolimod
Description
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Title
PK Parameter: %AUCexp of Vesatolimod
Description
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Title
PK Parameter: Cmax of Vesatolimod
Description
Cmax is defined as the maximum concentration of drug.
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Title
PK Parameter: Clast of Vesatolimod
Description
Clast is defined as the last observable concentration of drug.
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Title
PK Parameter: Tmax of Vesatolimod
Description
Tmax is defined as the time (observed time point) of Cmax
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Title
PK Parameter: Tlast of Vesatolimod
Description
Tlast is defined as the time (observed time point) of Clast.
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Title
PK Parameter: T1/2 of Vesatolimod
Description
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Title
PK Parameter: CL/F of Vesatolimod
Description
CL/F is defined as the apparent oral clearance following administration of the drug.
Time Frame
Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Adult males or females between the ages of 18-65
Chronic hepatitis B virus (HBV) infection
HBV deoxyribonucleic acid (DNA ) ≥ 2000 IU/mL at screening
Key Exclusion Criteria:
Extensive bridging fibrosis or cirrhosis
Received oral antiviral treatment for HBV or prolonged therapy with immune-modulators or biologics within 3 months of screening
Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV) or hepatitis D virus (HDV)
Chronic liver disease other than HBV
Lactating or pregnant females or those that wish to become pregnant during the course of the study
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
Palo Alto
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
Honolulu
State/Province
Hawaii
Country
United States
City
Catonsville
State/Province
Maryland
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Flushing
State/Province
New York
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Toronto
State/Province
Ontario
Country
Canada
City
Kowloon
Country
Hong Kong
City
Bologna
Country
Italy
City
Milano
Country
Italy
City
Pisa
Country
Italy
City
San Giovanni Rotondo
Country
Italy
City
Daegu
Country
Korea, Republic of
City
Seoul
Country
Korea, Republic of
City
Grafton
State/Province
Auckland
Country
New Zealand
City
Dalin
Country
Taiwan
City
Kaohsiung
Country
Taiwan
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29851204
Citation
Agarwal K, Ahn SH, Elkhashab M, Lau AH, Gaggar A, Bulusu A, Tian X, Cathcart AL, Woo J, Subramanian GM, Andreone P, Kim HJ, Chuang WL, Nguyen MH. Safety and efficacy of vesatolimod (GS-9620) in patients with chronic hepatitis B who are not currently on antiviral treatment. J Viral Hepat. 2018 Nov;25(11):1331-1340. doi: 10.1111/jvh.12942. Epub 2018 Aug 22.
Results Reference
result
Citation
Younossi ZM, Stepanova M, Janssen H, Agarwal K, Nguyen MH, Gane EJ, et al. The impact of treatment of chronic hepatitis B (CHB) on patient reported outcomes (PROs). Poster 1924. AASLD 2017. Hepatology; 66:1020A, 2017.
Results Reference
result
Citation
Lau A, Joshi A, Nguyen AH, Gaggar A, Patterson SD, Woo J. Peripheral blood immune cell profiling in virally suppressed chronic hepatitis B (CHB) patients and CHB patients not on an oral antiviral therapy. HBV International Meeting 2017.
Results Reference
result
Learn more about this trial
Study to Evaluate the Safety, Tolerability, and Efficacy of Vesatolimod in Combination With Tenofovir Disoproxil Fumarate (TDF) in Adults With Chronic Hepatitis B (CHB) Infection Who Are Currently Not Being Treated
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