Back to resultsStudy To Evaluate Safety and Efficacy of Vesatolimod for the Treatment of Chronic Hepatitis B Virus in Virally-Suppressed Participants
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vesatolimod
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Hepatitis B, HBV, GS-9620, TLR-7 Agonist
Eligibility Criteria
Key Inclusion Criteria:
- Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
- Documented evidence of CHB infection (eg, hepatitis B surface antigen [HBsAg] positive for more than 6 months) with detectable HBsAg levels at screening
- Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below lower limit of quantitation (LLOQ), measured at least once, 6 or more months prior to screening, and HBV DNA < 20 IU/mL at screening
- 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
- Willing to provide blood sample for toll-like receptor 7 (TLR-7) and interleukin 28 B (IL28B) single-nucleotide polymorphism (SNP) assessment
- Must be willing and able to comply with all study requirements
Key Exclusion Criteria:
- Extensive bridging fibrosis or cirrhosis
- Laboratory parameters not within defined thresholds for neutropenia, anemia, thrombocytopenia, leukopenia, or other evidence of inadequate liver function
- Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
- Evidence of hepatocellular carcinoma
- Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Participants under evaluation for possible malignancy are not eligible.
- Significant cardiovascular, pulmonary, or neurological disease
Any of the following conditions that may worsen in response to interferon (IFN):
- Autoimmune disease (eg, 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 (eg, chronic obstructive pulmonary disease)
- Retinal disease
- Immunodeficiency disorders
- Received solid organ or bone marrow transplant
- Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal Ab, interferon) within 3 months of screening
- Use of another investigational agents within 3 months of screening
- Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
- Females who are pregnant or may wish to become pregnant during 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 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo 4 Weeks (Cohort A)
Vesatolimod 1 mg 4 Weeks (Cohort A)
Vesatolimod 2 mg 4 Weeks (Cohort A)
Vesatolimod 4 mg 4 Weeks (Cohort A)
Placebo 8 Weeks (Cohort B)
Vesatolimod 1 mg 8 Weeks (Cohort B)
Vesatolimod 2 mg 8 Weeks (Cohort B)
Vesatolimod 4 mg 8 Weeks (Cohort B)
Placebo 12 Weeks (Cohort C)
Vesatolimod 1 mg 12 Weeks (Cohort C)
Vesatolimod 2 mg 12 Weeks (Cohort C)
Vesatolimod 4 mg 12 Weeks (Cohort C)
Arm Description
Placebo tablet once a week for 4 weeks
Vesatolimod 1 mg tablet once a week for 4 weeks
Vesatolimod 2 mg tablet once a week for 4 weeks
Vesatolimod 4 mg tablet once a week for 4 weeks
Placebo tablet once a week for 8 weeks
Vesatolimod 1 mg tablet once a week for 8 weeks
Vesatolimod 2 mg tablet once a week for 8 weeks
Vesatolimod 4 mg tablet once a week for 8 weeks
Placebo tablet once a week for 12 weeks
Vesatolimod 1 mg tablet once a week for 12 weeks
Vesatolimod 2 mg tablet once a week for 12 weeks
Vesatolimod 4 mg tablet once a week for 12 weeks
Outcomes
Primary Outcome Measures
Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24
A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.
Secondary Outcome Measures
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window.
HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window.
Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window.
HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window.
Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
Only participants who were HBeAg+ at baseline were included.
Composite Endpoint Measuring the 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 within the targeted time window.
HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window.
Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
Composite Endpoint Measuring the 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 within the targeted time window.
HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window.
Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
Change From Baseline in Serum HBsAg Level at Week 4
Change From Baseline in Serum HBsAg Level at Week 8
Change From Baseline in Serum HBsAg Level at Week 12
Change From Baseline in Serum HBsAg Level at Week 48
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02166047
Brief Title
Study To Evaluate Safety and Efficacy of Vesatolimod for the Treatment of Chronic Hepatitis B Virus in Virally-Suppressed Participants
Official Title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
June 30, 2014 (Actual)
Primary Completion Date
May 11, 2016 (Actual)
Study Completion Date
October 20, 2016 (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 in participants with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV).
Participants will be randomized in 3 sequential cohorts (Cohorts A, B, and C). Within each cohort, participants will be randomized in a 1:3:3:3 ratio to placebo or one of the doses of vesatolimod (1, 2, or 4 mg).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Hepatitis B, HBV, GS-9620, TLR-7 Agonist
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
162 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo 4 Weeks (Cohort A)
Arm Type
Placebo Comparator
Arm Description
Placebo tablet once a week for 4 weeks
Arm Title
Vesatolimod 1 mg 4 Weeks (Cohort A)
Arm Type
Experimental
Arm Description
Vesatolimod 1 mg tablet once a week for 4 weeks
Arm Title
Vesatolimod 2 mg 4 Weeks (Cohort A)
Arm Type
Experimental
Arm Description
Vesatolimod 2 mg tablet once a week for 4 weeks
Arm Title
Vesatolimod 4 mg 4 Weeks (Cohort A)
Arm Type
Experimental
Arm Description
Vesatolimod 4 mg tablet once a week for 4 weeks
Arm Title
Placebo 8 Weeks (Cohort B)
Arm Type
Placebo Comparator
Arm Description
Placebo tablet once a week for 8 weeks
Arm Title
Vesatolimod 1 mg 8 Weeks (Cohort B)
Arm Type
Experimental
Arm Description
Vesatolimod 1 mg tablet once a week for 8 weeks
Arm Title
Vesatolimod 2 mg 8 Weeks (Cohort B)
Arm Type
Experimental
Arm Description
Vesatolimod 2 mg tablet once a week for 8 weeks
Arm Title
Vesatolimod 4 mg 8 Weeks (Cohort B)
Arm Type
Experimental
Arm Description
Vesatolimod 4 mg tablet once a week for 8 weeks
Arm Title
Placebo 12 Weeks (Cohort C)
Arm Type
Placebo Comparator
Arm Description
Placebo tablet once a week for 12 weeks
Arm Title
Vesatolimod 1 mg 12 Weeks (Cohort C)
Arm Type
Experimental
Arm Description
Vesatolimod 1 mg tablet once a week for 12 weeks
Arm Title
Vesatolimod 2 mg 12 Weeks (Cohort C)
Arm Type
Experimental
Arm Description
Vesatolimod 2 mg tablet once a week for 12 weeks
Arm Title
Vesatolimod 4 mg 12 Weeks (Cohort C)
Arm Type
Experimental
Arm Description
Vesatolimod 4 mg tablet once a week for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Vesatolimod
Other Intervention Name(s)
GS-9620
Intervention Description
Vesatolimod tablet administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to match vesatolimod tablet administered orally
Primary Outcome Measure Information:
Title
Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24
Description
A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window.
HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window.
Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
Time Frame
Week 24
Title
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window.
HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window.
Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
Only participants who were HBeAg+ at baseline were included.
Time Frame
Week 48
Title
Composite Endpoint Measuring the 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 within the targeted time window.
HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window.
Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
Time Frame
Week 24
Title
Composite Endpoint Measuring the 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 within the targeted time window.
HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window.
Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
Time Frame
Week 48
Title
Change From Baseline in Serum HBsAg Level at Week 4
Time Frame
Baseline; Week 4
Title
Change From Baseline in Serum HBsAg Level at Week 8
Time Frame
Baseline; Week 8
Title
Change From Baseline in Serum HBsAg Level at Week 12
Time Frame
Baseline; Week 12
Title
Change From Baseline in Serum HBsAg Level at Week 48
Time Frame
Baseline; Week 48
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:
Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
Documented evidence of CHB infection (eg, hepatitis B surface antigen [HBsAg] positive for more than 6 months) with detectable HBsAg levels at screening
Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below lower limit of quantitation (LLOQ), measured at least once, 6 or more months prior to screening, and HBV DNA < 20 IU/mL at screening
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
Willing to provide blood sample for toll-like receptor 7 (TLR-7) and interleukin 28 B (IL28B) single-nucleotide polymorphism (SNP) assessment
Must be willing and able to comply with all study requirements
Key Exclusion Criteria:
Extensive bridging fibrosis or cirrhosis
Laboratory parameters not within defined thresholds for neutropenia, anemia, thrombocytopenia, leukopenia, or other evidence of inadequate liver function
Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
Evidence of hepatocellular carcinoma
Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Participants under evaluation for possible malignancy are not eligible.
Significant cardiovascular, pulmonary, or neurological disease
Any of the following conditions that may worsen in response to interferon (IFN):
Autoimmune disease (eg, 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 (eg, chronic obstructive pulmonary disease)
Retinal disease
Immunodeficiency disorders
Received solid organ or bone marrow transplant
Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal Ab, interferon) within 3 months of screening
Use of another investigational agents within 3 months of screening
Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
Females who are pregnant or may wish to become pregnant during 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
ZIP/Postal Code
90095
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92154
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94118
Country
United States
City
San Jose
State/Province
California
ZIP/Postal Code
95128
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96734
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
City
Flushing
State/Province
New York
ZIP/Postal Code
11355
Country
United States
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 3P4
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2C4
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
City
San Giovanni Rotondo
State/Province
FG
ZIP/Postal Code
71013
Country
Italy
City
Milan
ZIP/Postal Code
20122
Country
Italy
City
Parma
ZIP/Postal Code
43126
Country
Italy
City
Pisa
ZIP/Postal Code
56124
Country
Italy
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
City
Auckland
ZIP/Postal Code
1142
Country
New Zealand
12. IPD Sharing Statement
Citations:
PubMed Identifier
29378197
Citation
Boni C, Vecchi A, Rossi M, Laccabue D, Giuberti T, Alfieri A, Lampertico P, Grossi G, Facchetti F, Brunetto MR, Coco B, Cavallone D, Mangia A, Santoro R, Piazzolla V, Lau A, Gaggar A, Subramanian GM, Ferrari C. TLR7 Agonist Increases Responses of Hepatitis B Virus-Specific T Cells and Natural Killer Cells in Patients With Chronic Hepatitis B Treated With Nucleos(T)Ide Analogues. Gastroenterology. 2018 May;154(6):1764-1777.e7. doi: 10.1053/j.gastro.2018.01.030. Epub 2018 Jan 31.
Results Reference
result
PubMed Identifier
29104121
Citation
Janssen HLA, Brunetto MR, Kim YJ, Ferrari C, Massetto B, Nguyen AH, Joshi A, Woo J, Lau AH, Gaggar A, Subramanian GM, Yoshida EM, Ahn SH, Tsai NCS, Fung S, Gane EJ. Safety, efficacy and pharmacodynamics of vesatolimod (GS-9620) in virally suppressed patients with chronic hepatitis B. J Hepatol. 2018 Mar;68(3):431-440. doi: 10.1016/j.jhep.2017.10.027. Epub 2017 Dec 11.
Results Reference
result
Learn more about this trial
Study To Evaluate Safety and Efficacy of Vesatolimod for the Treatment of Chronic Hepatitis B Virus in Virally-Suppressed Participants
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