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NCT02174276

Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Participants With Chronic Hepatitis B (CHB) and Who Are Currently Not on Treatment

Completed Phase 2 Results posted Last updated 4 June 2019
What this trial tests

Phase 2 trial testing Tenofovir disoproxil fumarate in Chronic Hepatitis B in 195 participants. Completed in 30 May 2018.

Timeline
24 July 2014
Primary endpoint
17 February 2016
30 May 2018

Quick facts

Lead sponsorGilead Sciences
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment195
Start date24 July 2014
Primary completion17 February 2016
Estimated completion30 May 2018
Sites33 locations across Italy, New Zealand, South Korea, Romania, Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with Chronic Hepatitis B. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change in Serum HBsAg From Baseline to Week 24 Primary · Baseline to 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 treatment groups, ALT levels (\> ULN or ≤ ULN) at baseline, HBeAg status (positive or negative) at baseline, HBsAg level at baseline, visit and treatment-by-visit interaction as fixed effects and visit as a repeated measurement. Estimated least square means of treatment effects are presented with the 95% confidence intervals (CIs).

GroupValue95% CI
TDF 48 Weeks-0.079-0.192 – 0.035
TDF + GS-4774 2 YU-0.096-0.174 – -0.018
TDF + GS-4774 10 YU-0.016-0.095 – 0.064
TDF + GS-4774 40 YU-0.135-0.215 – -0.055
Mean Change in HBsAg From Baseline to Week 12 Secondary · Baseline to Week 12

The change from baseline to Week 12 in HBsAg was analyzed using a MMRM. The model included treatment groups, ALT levels (\> ULN or ≤ ULN) at baseline, HBeAg status (positive or negative) at baseline, HBsAg level at baseline, visit and treatment-by-visit interaction as fixed effects and visit as a repeated measurement. Estimated least square means of treatment effects are presented with the 95% CIs.

GroupValue95% CI
TDF 48 Weeks-0.060-0.165 – 0.044
TDF + GS-4774 2 YU-0.061-0.133 – 0.011
TDF + GS-4774 10 YU-0.012-0.086 – 0.061
TDF + GS-4774 40 YU-0.095-0.168 – -0.021
Mean Change in HBsAg From Baseline to Week 48 Secondary · Baseline to Week 48

The change from baseline to Week 48 in HBsAg was analyzed using a MMRM. The model included treatment groups, ALT levels (\> ULN or ≤ ULN) at baseline, HBeAg status (positive or negative) at baseline, HBsAg level at baseline, visit and treatment-by-visit interaction as fixed effects and visit as a repeated measurement. Estimated least square means of treatment effects are presented with the 95% CIs.

GroupValue95% CI
TDF 48 Weeks-0.145-0.272 – -0.017
TDF + GS-4774 2 YU-0.136-0.225 – -0.048
TDF + GS-4774 10 YU-0.086-0.176 – 0.004
TDF + GS-4774 40 YU-0.165-0.254 – -0.075
Percentage of Participants With HBsAg Loss at Week 24 Secondary · Baseline to Week 24

HBsAg loss was defined as qualitative HBsAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window.

GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU0.0
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU0.0
Percentage of Participants With HBsAg Loss at Week 48 Secondary · Baseline to Week 48

HBsAg loss was defined as qualitative HBsAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window.

GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU0.0
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU0.0
Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24 Secondary · Baseline to Week 24

HBsAg loss was defined as qualitative HBsAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg loss and seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit and the participant must have achieved HBsAg loss within the targeted time window.

GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU0.0
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU0.0
Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48 Secondary · Baseline to Week 48

HBsAg loss was defined as qualitative HBsAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg loss and seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit and the participant must have achieved HBsAg loss within the targeted time window.

GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU0.0
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU0.0
Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 12 Secondary · Baseline to Week 12

HBsAg with a ≥ 0.5 or ≥ 1.0 log10 IU/mL decline was defined as ≥ 0.5 or ≥ 1.0 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.

≥ 0.5 and < 1.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks3.7
TDF + GS-4774 2 YU3.5
TDF + GS-4774 10 YU1.8
TDF + GS-4774 40 YU5.5
≥ 1.0 and < 2.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU3.5
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU0.0
≥ 2.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU0.0
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU1.8
Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 24 Secondary · Baseline to Week 24

HBsAg with a ≥ 0.5 or ≥ 1.0 log10 IU/mL decline was defined as ≥ 0.5 or ≥ 1.0 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.

≥ 0.5 and < 1.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU1.8
TDF + GS-4774 10 YU1.8
TDF + GS-4774 40 YU7.3
≥ 1.0 and < 2.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU5.3
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU1.8
≥ 2.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU0.0
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU1.8
Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 48 Secondary · Baseline to Week 48

HBsAg with a ≥ 0.5 or ≥ 1.0 log10 IU/mL decline was defined as ≥ 0.5 or ≥ 1.0 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.

≥ 0.5 and < 1.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks11.1
TDF + GS-4774 2 YU1.8
TDF + GS-4774 10 YU7.1
TDF + GS-4774 40 YU7.3
≥ 1.0 and < 2.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU5.3
TDF + GS-4774 10 YU1.8
TDF + GS-4774 40 YU1.8
≥ 2.0 log10 IU/mL Decline
GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU0.0
TDF + GS-4774 10 YU0.0
TDF + GS-4774 40 YU1.8
Percentage of Participants With HBeAg Loss at Week 24 Secondary · Baseline to Week 24

HBeAg loss was defined as qualitative HBeAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window.

GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU0.0
TDF + GS-4774 10 YU4.3
TDF + GS-4774 40 YU0.0
Percentage of Participants With HBeAg Loss at Week 48 Secondary · Baseline to Week 48

HBeAg loss was defined as qualitative HBeAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window.

GroupValue95% CI
TDF 48 Weeks0.0
TDF + GS-4774 2 YU4.5
TDF + GS-4774 10 YU8.7
TDF + GS-4774 40 YU9.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events: First dose date up to last dose date (maximum exposure: 3 years); All-Cause Mortality: First dose date up to 3 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TDF 48 Weeks
Serious: 2/27 (7%)
Deaths: 0/27
TDF + GS-4774 2 YU
Serious: 1/57 (2%)
Deaths: 0/57
TDF + GS-4774 10 YU
Serious: 1/56 (2%)
Deaths: 0/56
TDF + GS-4774 40 YU
Serious: 1/55 (2%)
Deaths: 0/55

Serious adverse events (4 terms)

ReactionSystemTDF 48 WeeksTDF + GS-4774 2 YUTDF + GS-4774 10 YUTDF + GS-4774 40 YU
Meningitis tuberculousInfections and infestations————
Spinal fractureInjury, poisoning and procedural complications————
Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)————
Uterine polypReproductive system and breast disorders————
Other adverse events (38 terms — click to expand)

ReactionSystemTDF 48 WeeksTDF + GS-4774 2 YUTDF + GS-4774 10 YUTDF + GS-4774 40 YU
Injection site painGeneral disorders————
Injection site erythemaGeneral disorders————
FatigueGeneral disorders————
Injection site swellingGeneral disorders————
MyalgiaMusculoskeletal and connective tissue disorders————
HeadacheNervous system disorders————
Injection site indurationGeneral disorders————
Injection site pruritusGeneral disorders————
NauseaGastrointestinal disorders————
ChillsGeneral disorders————
NasopharyngitisInfections and infestations————
CoughRespiratory, thoracic and mediastinal disorders————
PyrexiaGeneral disorders————
Upper respiratory tract infectionInfections and infestations————
Back painMusculoskeletal and connective tissue disorders————
InfluenzaInfections and infestations————
HypertensionVascular disorders————
DyspepsiaGastrointestinal disorders————
Injection site oedemaGeneral disorders————
Injection site reactionGeneral disorders————
PainGeneral disorders————
InsomniaPsychiatric disorders————
Oropharyngeal painRespiratory, thoracic and mediastinal disorders————
DiarrhoeaGastrointestinal disorders————
Gastrooesophageal reflux diseaseGastrointestinal disorders————
AstheniaGeneral disorders————
Influenza like illnessGeneral disorders————
FolliculitisInfections and infestations————
SinusitisInfections and infestations————
Alanine aminotransferase increasedInvestigations————
Aspartate aminotransferase increasedInvestigations————
ArthralgiaMusculoskeletal and connective tissue disorders————
AlopeciaSkin and subcutaneous tissue disorders————
Ligament sprainInjury, poisoning and procedural complications————
Musculoskeletal painMusculoskeletal and connective tissue disorders————
Nasal congestionRespiratory, thoracic and mediastinal disorders————
Productive coughRespiratory, thoracic and mediastinal disorders————
RhinorrhoeaRespiratory, thoracic and mediastinal disorders————

Most-reported serious reactions: Meningitis tuberculous, Spinal fracture, Uterine leiomyoma, Uterine polyp.

Data from ClinicalTrials.gov NCT02174276 adverse events section.

Sponsor's own description

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of GS-4774 in adults with CHB and who are currently not on treatment. Participants will be randomized to receive TDF alone or GS-4774 plus TDF for 20 weeks. After Week 20, GS-4774 will be discontinued. All participants will continue on TDF and will be followed for an additional 28 weeks. Following completion of the 48 week study period, all participants will be eligible for a treatment extension for 96 weeks.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Present and future therapies of hepatitis B: From discovery to cure.
    Liang TJ, Block TM, McMahon BJ, Ghany MG, et al · · 2015 · cited 245× · PMID 26239691 · DOI 10.1002/hep.28025
  2. Combined GS-4774 and Tenofovir Therapy Can Improve HBV-Specific T-Cell Responses in Patients With Chronic Hepatitis.
    Boni C, Janssen HLA, Rossi M, Yoon SK, et al · · 2019 · cited 110× · PMID 30930022 · DOI 10.1053/j.gastro.2019.03.044
  3. Hepatitis B Virus Cure: Targets and Future Therapies.
    Lee HW, Lee JS, Ahn SH. · · 2020 · cited 75× · PMID 33379331 · DOI 10.3390/ijms22010213
  4. Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection.
    Meng Z, Chen Y, Lu M. · · 2019 · cited 75× · PMID 32117201 · DOI 10.3389/fimmu.2019.03127
  5. Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines.
    Criscuolo E, Caputo V, Diotti RA, Sautto GA, et al · · 2019 · cited 66× · PMID 30949518 · DOI 10.1155/2019/8303648
  6. Toward a complete cure for chronic hepatitis B: Novel therapeutic targets for hepatitis B virus.
    Kim SW, Yoon JS, Lee M, Cho Y. · · 2022 · cited 53× · PMID 34281294 · DOI 10.3350/cmh.2021.0093
  7. New Approaches to the Treatment of Chronic Hepatitis B.
    Alexopoulou A, Vasilieva L, Karayiannis P. · · 2020 · cited 50× · PMID 33019573 · DOI 10.3390/jcm9103187
  8. HBV Immune-Therapy: From Molecular Mechanisms to Clinical Applications.
    Boni C, Barili V, Acerbi G, Rossi M, et al · · 2019 · cited 42× · PMID 31195619 · DOI 10.3390/ijms20112754

Verify or expand the search:

Other trials of Tenofovir disoproxil fumarate

Trials testing the same drug.

Other recruiting trials for Chronic Hepatitis B

Currently open trials in the same condition.

Other Gilead Sciences trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02174276.

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