Chronic HBV InfectionPhase 2NCT01943799

Safety and Efficacy of GS-4774 for the Treatment of Chronic Hepatitis B

A Phase 2 study testing GS-4774 and OAV Regimen in people with Chronic HBV Infection, run by Gilead Sciences at 17 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Chronic HBV Infection
What is being tested?: GS-4774 and OAV Regimen
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 178 participants
Where: 17 sitesin 2 countries
Study dates: 13 Sep 2013to 3 Mar 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Show all 13Show fewer

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.

Trial locations and contacts

17 sites in 2 countries.

Country

City, postcode or hospital

17 sites in 2 countries

United States16 sites

University of Michigan
Ann Arbor, Michigan, 48109
Digestive Disease Associates, PA
Baltimore, Maryland, 21229
Tufts Medical Center
Boston, Massachusetts, 02111
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Henry Ford Hospital and Health System
Detroit, Michigan, 48202
Medical Pro-care
Flushing, New York, 11355
Dumont-UCLA Liver Transplant Center
Los Angeles, California, 90095
North Shore LIJ Health System
Manhasset, New York, 11030
University of Miami
Miami, Florida, 33136
Bon Secours St. Mary's Hospital of Richmond
Newport News, Virginia, 23602
Huntington Medical Research Institutes
Pasadena, California, 91105
Kaiser Permanente
Sacramento, California, 95825
Kaiser Permanente
San Diego, California, 92154
Kaiser Permanente
San Francisco, California, 94118
Silicon Valley Research Institute
San Jose, California, 95128
St.Louis University
St Louis, Missouri, 63104

Other trials in United States

New Zealand1 site

Auckland Clinical Studies
Grafton, 1141

Other trials in New Zealand

About this study

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

Conditions: Chronic HBV Infection
Being tested: GS-4774, OAV Regimen
Keywords: Hepatitis B (HBV), Oral antiviral (OAV), GS-4774
Medical subject headings: Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GS-4774Biological
Administered as a subcutaneous injection every 4 weeks for a total of 6 doses
OAV RegimenDrug
Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)

Study groups in NCT01943799
Study group	Role	What they receive
OAV Alone	Experimental	Participants will continue their prebaseline OAV regimen alone from baseline to Week 48. Receives: Drug: OAV Regimen
OAV + GS-4774 2 YU	Experimental	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. Receives: Biological: GS-4774; Drug: OAV Regimen
OAV + GS-4774 10 YU	Experimental	Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20. Receives: Biological: GS-4774; Drug: OAV Regimen
OAV + GS-4774 40 YU	Experimental	Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20. Receives: Biological: GS-4774; Drug: OAV Regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in HBsAg at 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.
Measured: Baseline; Week 24

Secondary outcomes (7)

Change From Baseline in HBsAg at 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.
Measured: Baseline; Week 12
Change From Baseline in HBsAg at 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.
Measured: Baseline; Week 48
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at 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.
Measured: Week 24
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at 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.
Measured: Week 48
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by 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.
Measured: Week 24
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by 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.
Measured: Week 48
Percentage of Participants With a 1-log Decline in HBsAg by 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.
Measured: Baseline; Weeks 12, 24, and 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Sep 20133 Mar 2015

First posted17 Sep 2013 (estimated)
Study start13 Sep 2013
Primary completion9 Sep 2014
Study completion3 Mar 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chronic HBV InfectionStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 178 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01943799
Sponsor's protocol ID: GS-US-330-0101
Status last verified: Oct 2019
First submitted: 12 Sep 2013
Last updated: 1 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Lok AS, Pan CQ, Han SH, Trinh HN, Fessel WJ, Rodell T, Massetto B, Lin L, Gaggar A, Subramanian GM, McHutchison JG, Ferrari C, Lee H, Gordon SC, Gane EJ. Randomized phase II study of GS-4774 as a therapeutic vaccine in virally suppressed patients with chronic hepatitis B. J Hepatol. 2016 Sep;65(3):509-16. doi: 10.1016/j.jhep.2016.05.016. Epub 2016 May 19.
PubMed 27210427

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

All Chronic HBV Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01943799
Acronym / sponsor ID: GS-US-330-0101
Conditions: Chronic HBV Infection
Keywords: Hepatitis B (HBV), Oral antiviral (OAV), GS-4774
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 178 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 13 Sep 2013 (actual)
Primary completion: 9 Sep 2014 (actual)
Study completion: 3 Mar 2015 (actual)
First posted: 17 Sep 2013 (estimated)
Results: Posted 1 Nov 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
OAV Alone	Experimental	Drug: OAV RegimenParticipants will continue their prebaseline OAV regimen alone from baseline to Week 48.
OAV + GS-4774 2 YU	Experimental	Biological: GS-4774, Drug: OAV RegimenParticipants 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.
OAV + GS-4774 10 YU	Experimental	Biological: GS-4774, Drug: OAV RegimenParticipants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20.
OAV + GS-4774 40 YU	Experimental	Biological: GS-4774, Drug: OAV RegimenParticipants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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 (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GS-4774Administered as a subcutaneous injection every 4 weeks for a total of 6 doses	Biological	OAV + GS-4774 10 YU, OAV + GS-4774 2 YU, OAV + GS-4774 40 YU
OAV RegimenAdministered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)	Drug	OAV + GS-4774 10 YU, OAV + GS-4774 2 YU, OAV + GS-4774 40 YU, OAV Alone

Primary outcome

Change From Baseline in HBsAg at Week 24
Time frame: 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.

7 secondary outcomes

Change From Baseline in HBsAg at Week 12
Time frame: Baseline; Week 12
Change From Baseline in HBsAg at Week 48
Time frame: Baseline; Week 48
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24
Time frame: Week 24
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48
Time frame: Week 48
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 24
Time frame: Week 24
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 48
Time frame: Week 48
Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48
Time frame: Baseline; Weeks 12, 24, and 48

Results and safety

Results posted to the registry on 1 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
OAV Alone (Group A)	27	22
OAV + GS-4774 2 YU (Group B)	50	47
OAV + GS-4774 10 YU (Group C)	51	49
OAV + GS-4774 40 YU (Group D)	50	50

Primary outcome: Change From Baseline in HBsAg at Week 24

Time frame: Baseline; Week 24. Least squares mean (95% Confidence Interval). Unit: log10 IU/mL

Measure	OAV Alone (Group A) n = 21	OAV + GS-4774 2 YU (Group B) n = 47	OAV + GS-4774 10 YU (Group C) n = 48	OAV + GS-4774 40 YU (Group D) n = 49
Value	-0.019 (-0.070 to 0.031)	-0.020 (-0.055 to 0.014)	-0.026 (-0.060 to 0.008)	-0.048 (-0.082 to -0.014)

OAV Alone (Group A) vs OAV + GS-4774 2 YU (Group B): LS Mean Difference: -0.001 (95% CI -0.061 to 0.059), p = 0.976, MMRM
OAV Alone (Group A) vs OAV + GS-4774 10 YU (Group C): LS Mean Difference: -0.007 (95% CI -0.067 to 0.053), p = 0.828, MMRM
OAV Alone (Group A) vs OAV + GS-4774 40 YU (Group D): LS Mean Difference: -0.029 (95% CI -0.089 to 0.031), p = 0.343, MMRM

Population analysed: 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.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: First dose date up to Week 20 plus 28 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
OAV Alone (Group A)	0 of 27 (0%)	7 of 27 (25.9%)	0 of 27
OAV + GS-4774 2 YU (Group B)	1 of 50 (2%)	39 of 50 (78%)	0 of 50
OAV + GS-4774 10 YU (Group C)	1 of 51 (2%)	47 of 51 (92.2%)	0 of 51
OAV + GS-4774 40 YU (Group D)	0 of 50 (0%)	46 of 50 (92%)	0 of 50

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27210427Lok AS, Pan CQ, Han SH, Trinh HN, Fessel WJ, Rodell T, Massetto B, Lin L, Gaggar A, Subramanian GM, McHutchison JG, Ferrari C, Lee H, Gordon SC, Gane EJ. Randomized phase II study of GS-4774 as a therapeutic vaccine in virally suppressed patients with chronic hepatitis B. J Hepatol. 2016 Sep;65(3):509-16. doi: 10.1016/j.jhep.2016.05.016. Epub 2016 May 19.

Related trials for Chronic HBV Infection

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

17 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GS-4774 and OAV Regimen in people with Chronic HBV Infection, run by Gilead Sciences at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in HBsAg at Week 24 (time frame: Baseline; Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01943799, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.