Safety and Efficacy of GS-4774 for the Treatment of Chronic Hepatitis B
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01943799
Collaborator
(none)
178
17
4
17.6
10.5
0.6
Study Details
Study Description
Brief Summary
The primary objectives of this study are to evaluate the safety and efficacy of GS-4774 in adults with chronic hepatitis B (CHB) viral infection who have been virally suppressed with an oral antiviral (OAV) medication.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
178 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B
Actual Study Start Date
:
Sep 13, 2013
Actual Primary Completion Date
:
Sep 9, 2014
Actual Study Completion Date
:
Mar 3, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: OAV Alone Participants will continue their prebaseline OAV regimen alone from baseline to Week 48. |
Drug: OAV Regimen
Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
|
| Experimental: OAV + GS-4774 2 YU Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 2 yeast units (YU) from baseline to Week 20. |
Biological: GS-4774
Administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Drug: OAV Regimen
Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
|
| Experimental: OAV + GS-4774 10 YU Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20. |
Biological: GS-4774
Administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Drug: OAV Regimen
Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
|
| Experimental: OAV + GS-4774 40 YU Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20. |
Biological: GS-4774
Administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Drug: OAV Regimen
Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in HBsAg at Week 24 [Baseline; Week 24]
The change from baseline to Week 24 in HBsAg was analyzed using a mixed effect model for repeated measures (MMRM). The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.
Secondary Outcome Measures
- Change From Baseline in HBsAg at Week 12 [Baseline; Week 12]
The change from baseline to Week 12 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.
- Change From Baseline in HBsAg at Week 48 [Baseline; Week 48]
The change from baseline to Week 48 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.
- Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24 [Week 24]
HBsAg loss was defined as HBsAg level decreasing from >0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from < 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit.
- Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48 [Week 48]
HBsAg loss was defined as HBsAg level decreasing from >0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from < 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit.
- Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 24 [Week 24]
HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit.
- Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 48 [Week 48]
HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit.
- Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48 [Baseline; Weeks 12, 24, and 48]
HBsAg 1-log decline was defined as ≥ 1 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
-
Currently taking an approved HBV oral antiviral medication
-
Documented evidence of chronic HBV infection (eg, HBsAg positive for more than 6 months)
-
Virally-suppressed (HBV DNA below the lower limit of quantification (LLOQ) for ≥ 1 year)
Key Exclusion Criteria:
-
Cirrhosis
-
Inadequate liver function
-
Co-infection with hepatitic C virus (HCV), HIV or hepatitic D virus (HDV)
-
Evidence of hepatocellular carcinoma
-
Significant cardiovascular, pulmonary, or neurological disease
-
Females who are pregnant or may wish to become pregnant during the study
-
Received solid organ or bone marrow transplant
-
Use of another investigational agents within 3 months of screening
-
Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
-
History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease ulcerative colitis, autoimmune disease
-
Known hypersensitivity to study drug, metabolites or formulation excipients
-
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.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dumont-UCLA Liver Transplant Center | Los Angeles | California | United States | 90095 |
| 2 | Huntington Medical Research Institutes | Pasadena | California | United States | 91105 |
| 3 | Kaiser Permanente | Sacramento | California | United States | 95825 |
| 4 | Kaiser Permanente | San Diego | California | United States | 92154 |
| 5 | Kaiser Permanente | San Francisco | California | United States | 94118 |
| 6 | Silicon Valley Research Institute | San Jose | California | United States | 95128 |
| 7 | University of Miami | Miami | Florida | United States | 33136 |
| 8 | Northwestern Memorial Hospital | Chicago | Illinois | United States | 60611 |
| 9 | Digestive Disease Associates, PA | Baltimore | Maryland | United States | 21229 |
| 10 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
| 11 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 12 | Henry Ford Hospital and Health System | Detroit | Michigan | United States | 48202 |
| 13 | St.Louis University | Saint Louis | Missouri | United States | 63104 |
| 14 | Medical Pro-care | Flushing | New York | United States | 11355 |
| 15 | North Shore LIJ Health System | Manhasset | New York | United States | 11030 |
| 16 | Bon Secours St. Mary's Hospital of Richmond | Newport News | Virginia | United States | 23602 |
| 17 | Auckland Clinical Studies | Grafton | New Zealand | 1141 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01943799
Other Study ID Numbers:
- GS-US-330-0101
First Posted:
Sep 17, 2013
Last Update Posted:
Nov 1, 2019
Last Verified:
Oct 1, 2019
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Gilead Sciences
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at study sites in United States and New Zealand. The first participant was screened on 13 September 2013. The last study visit occurred on 03 March 2015. |
|---|---|
| Pre-assignment Detail | 213 participants were screened. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline oral antiviral (OAV) regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 yeast units (YU) administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Period Title: Overall Study | ||||
| STARTED | 27 | 50 | 51 | 50 |
| COMPLETED | 22 | 47 | 49 | 50 |
| NOT COMPLETED | 5 | 3 | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Total of all reporting groups |
| Overall Participants | 27 | 50 | 51 | 50 | 178 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
45
(10.9)
|
50
(9.0)
|
47
(10.0)
|
47
(11.1)
|
47
(10.2)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
7
25.9%
|
16
32%
|
14
27.5%
|
19
38%
|
56
31.5%
|
| Male |
20
74.1%
|
34
68%
|
37
72.5%
|
31
62%
|
122
68.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
2
4%
|
1
2%
|
1
2%
|
4
2.2%
|
| Not Hispanic or Latino |
27
100%
|
48
96%
|
50
98%
|
49
98%
|
174
97.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Asian |
21
77.8%
|
40
80%
|
41
80.4%
|
34
68%
|
136
76.4%
|
| White |
5
18.5%
|
6
12%
|
3
5.9%
|
7
14%
|
21
11.8%
|
| Other |
1
3.7%
|
3
6%
|
4
7.8%
|
2
4%
|
10
5.6%
|
| Black or African American |
0
0%
|
1
2%
|
2
3.9%
|
5
10%
|
8
4.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
1
2%
|
1
2%
|
2
1.1%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
2%
|
1
0.6%
|
| Region of Enrollment (Count of Participants) | |||||
| New Zealand |
4
14.8%
|
6
12%
|
2
3.9%
|
7
14%
|
19
10.7%
|
| United States |
23
85.2%
|
44
88%
|
49
96.1%
|
43
86%
|
159
89.3%
|
| Hepatitis B Surface Antigen (HBsAg) (log10 IU/mL) (log10 IU/mL) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [log10 IU/mL] |
2.5
(1.46)
|
3.1
(0.72)
|
3.0
(1.02)
|
3.0
(0.86)
|
2.9
(0.99)
|
| HBsAg Level (Count of Participants) | |||||
| ≤ 1000 IU/mL |
13
48.1%
|
18
36%
|
21
41.2%
|
21
42%
|
73
41%
|
| > 1000 IU/mL |
14
51.9%
|
32
64%
|
30
58.8%
|
29
58%
|
105
59%
|
| Hepatitis B Envelope Antigen (HBeAg) Status (Count of Participants) | |||||
| Positive |
7
25.9%
|
13
26%
|
12
23.5%
|
12
24%
|
44
24.7%
|
| Negative |
20
74.1%
|
37
74%
|
39
76.5%
|
38
76%
|
134
75.3%
|
Outcome Measures
| Title | Change From Baseline in HBsAg at Week 24 |
|---|---|
| Description | The change from baseline to Week 24 in HBsAg was analyzed using a mixed effect model for repeated measures (MMRM). The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure. |
| Time Frame | Baseline; Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set (participants who were randomized and had a Baseline/Day 1 visit for Treatment Group A or have received at least 1 dose of GS-4774 for Treatment Group B, C, and D) with available data were analyzed. Participants were analyzed according to the randomized treatment assignment. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Measure Participants | 21 | 47 | 48 | 49 |
| Least Squares Mean (95% Confidence Interval) [log10 IU/mL] |
-0.019
|
-0.020
|
-0.026
|
-0.048
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | OAV Alone (Group A), OAV + GS-4774 2 YU (Group B) |
|---|---|---|
| Comments | Each null hypothesis was tested against the 2-sided alternative that the mean change from baseline in serum HBsAg (log10 IU/mL) titers in the respective GS-4774 group was not equal to that of the OAV group. Estimated least squares means (LSM) of treatment effects and estimated differences in treatment effects between GS-4774 treatment groups and the OAV group at Week 24 were calculated with 95% confidence intervals (CIs) and unadjusted p-values. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.976 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.001 | |
| Confidence Interval |
(2-Sided) 95% -0.061 to 0.059 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | OAV Alone (Group A), OAV + GS-4774 10 YU (Group C) |
|---|---|---|
| Comments | Each null hypothesis was tested against the 2-sided alternative that the mean change from baseline in serum HBsAg (log10 IU/mL) titers in the respective GS-4774 group was not equal to that of the OAV group. Estimated least squares means (LSM) of treatment effects and estimated differences in treatment effects between GS-4774 treatment groups and the OAV group at Week 24 were calculated with 95% confidence intervals (CIs) and unadjusted p-values. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.828 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.007 | |
| Confidence Interval |
(2-Sided) 95% -0.067 to 0.053 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | OAV Alone (Group A), OAV + GS-4774 40 YU (Group D) |
|---|---|---|
| Comments | Each null hypothesis was tested against the 2-sided alternative that the mean change from baseline in serum HBsAg (log10 IU/mL) titers in the respective GS-4774 group was not equal to that of the OAV group. Estimated least squares means (LSM) of treatment effects and estimated differences in treatment effects between GS-4774 treatment groups and the OAV group at Week 24 were calculated with 95% confidence intervals (CIs) and unadjusted p-values. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.343 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.029 | |
| Confidence Interval |
(2-Sided) 95% -0.089 to 0.031 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in HBsAg at Week 12 |
|---|---|
| Description | The change from baseline to Week 12 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure. |
| Time Frame | Baseline; Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Measure Participants | 21 | 48 | 49 | 49 |
| Least Squares Mean (95% Confidence Interval) [log10 IU/mL] |
-0.004
|
-0.016
|
-0.017
|
-0.028
|
| Title | Change From Baseline in HBsAg at Week 48 |
|---|---|
| Description | The change from baseline to Week 48 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure. |
| Time Frame | Baseline; Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Measure Participants | 20 | 48 | 48 | 49 |
| Least Squares Mean (95% Confidence Interval) [log10 IU/mL] |
-0.043
|
-0.055
|
-0.051
|
-0.166
|
| Title | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24 |
|---|---|
| Description | HBsAg loss was defined as HBsAg level decreasing from >0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from < 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with HBsAg Level above 0.066 IU/mL at Baseline were analyzed. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Measure Participants | 25 | 50 | 50 | 50 |
| HBsAg Loss |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| HBsAg Loss and Seroconversion |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48 |
|---|---|
| Description | HBsAg loss was defined as HBsAg level decreasing from >0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from < 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with HBsAg Level above 0.066 IU/mL at Baseline were analyzed. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Measure Participants | 25 | 50 | 50 | 50 |
| HBsAg Loss |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| HBsAg Loss and Seroconversion |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 24 |
|---|---|
| Description | HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with positive HBeAg at baseline were analyzed. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Measure Participants | 7 | 13 | 12 | 12 |
| HBeAg Loss |
0
0%
|
0
0%
|
25.0
49%
|
0
0%
|
| HBeAg Loss and Seroconversion |
0
0%
|
0
0%
|
25.0
49%
|
0
0%
|
| Title | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 48 |
|---|---|
| Description | HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with positive HBeAg at baseline were analyzed. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Measure Participants | 7 | 13 | 12 | 12 |
| HBeAg Loss |
0
0%
|
7.7
15.4%
|
33.3
65.3%
|
0
0%
|
| HBeAg Loss and Seroconversion |
0
0%
|
7.7
15.4%
|
25.0
49%
|
0
0%
|
| Title | Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48 |
|---|---|
| Description | HBsAg 1-log decline was defined as ≥ 1 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window. |
| Time Frame | Baseline; Weeks 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) |
|---|---|---|---|---|
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. |
| Measure Participants | 27 | 51 | 50 | 50 |
| ≥ 1 log10 IU/mL Decline at Week 12 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ≥ 1 log10 IU/mL Decline at Week 24 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ≥ 1 log10 IU/mL Decline at Week 48 |
0
0%
|
0
0%
|
0
0%
|
2.0
4%
|
Adverse Events
| Time Frame | First dose date up to Week 20 plus 28 days | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU. | |||||||
| Arm/Group Title | OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) | ||||
| Arm/Group Description | Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination. | ||||
All Cause Mortality |
||||||||
| OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/27 (0%) | 0/50 (0%) | 0/51 (0%) | 0/50 (0%) | ||||
Serious Adverse Events |
||||||||
| OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/27 (0%) | 1/50 (2%) | 1/51 (2%) | 0/50 (0%) | ||||
| Infections and infestations | ||||||||
| Colonic abscess | 0/27 (0%) | 0/50 (0%) | 1/51 (2%) | 0/50 (0%) | ||||
| Psychiatric disorders | ||||||||
| Suicide attempt | 0/27 (0%) | 1/50 (2%) | 0/51 (0%) | 0/50 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| OAV Alone (Group A) | OAV + GS-4774 2 YU (Group B) | OAV + GS-4774 10 YU (Group C) | OAV + GS-4774 40 YU (Group D) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/27 (25.9%) | 39/50 (78%) | 47/51 (92.2%) | 46/50 (92%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea | 0/27 (0%) | 3/50 (6%) | 4/51 (7.8%) | 6/50 (12%) | ||||
| General disorders | ||||||||
| Chills | 0/27 (0%) | 2/50 (4%) | 5/51 (9.8%) | 7/50 (14%) | ||||
| Fatigue | 0/27 (0%) | 8/50 (16%) | 13/51 (25.5%) | 13/50 (26%) | ||||
| Injection site erythema | 0/27 (0%) | 18/50 (36%) | 29/51 (56.9%) | 36/50 (72%) | ||||
| Injection site induration | 0/27 (0%) | 18/50 (36%) | 21/51 (41.2%) | 23/50 (46%) | ||||
| Injection site pain | 0/27 (0%) | 19/50 (38%) | 34/51 (66.7%) | 39/50 (78%) | ||||
| Injection site pruritus | 0/27 (0%) | 13/50 (26%) | 16/51 (31.4%) | 26/50 (52%) | ||||
| Injection site swelling | 0/27 (0%) | 12/50 (24%) | 17/51 (33.3%) | 25/50 (50%) | ||||
| Pyrexia | 0/27 (0%) | 1/50 (2%) | 0/51 (0%) | 4/50 (8%) | ||||
| Infections and infestations | ||||||||
| Influenza | 2/27 (7.4%) | 1/50 (2%) | 1/51 (2%) | 1/50 (2%) | ||||
| Nasopharyngitis | 0/27 (0%) | 5/50 (10%) | 8/51 (15.7%) | 1/50 (2%) | ||||
| Upper respiratory tract infection | 3/27 (11.1%) | 2/50 (4%) | 2/51 (3.9%) | 3/50 (6%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/27 (0%) | 1/50 (2%) | 1/51 (2%) | 3/50 (6%) | ||||
| Back pain | 0/27 (0%) | 2/50 (4%) | 2/51 (3.9%) | 3/50 (6%) | ||||
| Musculoskeletal pain | 0/27 (0%) | 3/50 (6%) | 1/51 (2%) | 0/50 (0%) | ||||
| Myalgia | 0/27 (0%) | 4/50 (8%) | 7/51 (13.7%) | 13/50 (26%) | ||||
| Pain in extremity | 2/27 (7.4%) | 3/50 (6%) | 2/51 (3.9%) | 1/50 (2%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 0/27 (0%) | 3/50 (6%) | 2/51 (3.9%) | 2/50 (4%) | ||||
| Headache | 1/27 (3.7%) | 9/50 (18%) | 7/51 (13.7%) | 8/50 (16%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/27 (0%) | 5/50 (10%) | 6/51 (11.8%) | 3/50 (6%) | ||||
| Nasal congestion | 0/27 (0%) | 0/50 (0%) | 3/51 (5.9%) | 1/50 (2%) | ||||
| Oropharyngeal pain | 0/27 (0%) | 3/50 (6%) | 4/51 (7.8%) | 2/50 (4%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/27 (0%) | 3/50 (6%) | 0/51 (0%) | 0/50 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
| Name/Title | Gilead Clinical Study Information Center |
|---|---|
| Organization | Gilead Sciences |
| Phone | 1-833-445-3230 (GILEAD-0) |
| GileadClinicalTrials@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01943799
Other Study ID Numbers:
- GS-US-330-0101
First Posted:
Sep 17, 2013
Last Update Posted:
Nov 1, 2019
Last Verified:
Oct 1, 2019