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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

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ClinicalTrials.gov Identifier: NCT02174276
Recruitment Status : Completed
First Posted : June 25, 2014
Results First Posted : June 4, 2019
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: Tenofovir disoproxil fumarate Biological: GS-4774 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 195 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 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment
Actual Study Start Date : July 24, 2014
Actual Primary Completion Date : February 17, 2016
Actual Study Completion Date : May 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: TDF 48 weeks
Participants will receive TDF for 48 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
Drug: Tenofovir disoproxil fumarate
TDF 300 mg tablet administered orally once daily
Other Names:
  • TDF
  • Viread®

Experimental: TDF plus GS-4774 2 YU
Participants will receive TDF plus GS-4774 2 yeast units (YU) for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
Drug: Tenofovir disoproxil fumarate
TDF 300 mg tablet administered orally once daily
Other Names:
  • TDF
  • Viread®

Biological: GS-4774
GS-4774 subcutaneous injection administered every 4 weeks for a total of 6 doses

Experimental: TDF plus GS-4774 10 YU
Participants will receive TDF plus GS-4774 10 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
Drug: Tenofovir disoproxil fumarate
TDF 300 mg tablet administered orally once daily
Other Names:
  • TDF
  • Viread®

Biological: GS-4774
GS-4774 subcutaneous injection administered every 4 weeks for a total of 6 doses

Experimental: TDF plus GS-4774 40 YU
Participants will receive TDF plus GS-4774 40 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
Drug: Tenofovir disoproxil fumarate
TDF 300 mg tablet administered orally once daily
Other Names:
  • TDF
  • Viread®

Biological: GS-4774
GS-4774 subcutaneous injection administered every 4 weeks for a total of 6 doses




Primary Outcome Measures :
  1. Mean Change in Serum HBsAg From Baseline to Week 24 [ Time Frame: 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).


Secondary Outcome Measures :
  1. Mean Change in HBsAg From Baseline to Week 12 [ Time Frame: 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.

  2. Mean Change in HBsAg From Baseline to Week 48 [ Time Frame: 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.

  3. Percentage of Participants With HBsAg Loss at Week 24 [ Time Frame: 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.

  4. Percentage of Participants With HBsAg Loss at Week 48 [ Time Frame: 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.

  5. Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24 [ Time Frame: 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.

  6. Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48 [ Time Frame: 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.

  7. Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 12 [ Time Frame: 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.

  8. Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 24 [ Time Frame: 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.

  9. Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 48 [ Time Frame: 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.

  10. Percentage of Participants With HBeAg Loss at Week 24 [ Time Frame: 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.

  11. Percentage of Participants With HBeAg Loss at Week 48 [ Time Frame: 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.

  12. Composite Endpoint Measuring the Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 24 [ Time Frame: 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. HBeAg loss and seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit and the participant must have achieved HBeAg loss within the targeted time window.

  13. Composite Endpoint Measuring the Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 48 [ Time Frame: 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. HBeAg loss and seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit and the participant must have achieved HBeAg loss within the targeted time window.

  14. Percentage of Participants With HBV DNA < Lower Limit of Quantification (LLOQ) at Week 24 [ Time Frame: Week 24 ]
    The LLOQ was defined as 20 IU/mL.

  15. Percentage of Participants With HBV DNA < LLOQ at Week 48 [ Time Frame: Week 48 ]
    The LLOQ was defined as 20 IU/mL.

  16. Percentage of Participants Experiencing Virologic Breakthrough at Week 24 [ Time Frame: Baseline to Week 24 ]
    Virologic breakthrough was defined as HBV DNA ≥ 69 IU/mL after having been < 69 IU/mL, or having had ≥ 1.0 log10 increase in HBV DNA from nadir. Two consecutive visits that met the definition were required for a participant to be classified as having had virologic breakthrough.

  17. Percentage of Participants Experiencing Virologic Breakthrough at Week 48 [ Time Frame: Baseline to Week 48 ]
    Virologic breakthrough was defined as HBV DNA ≥ 69 IU/mL after having been < 69 IU/mL, or a ≥ 1.0 log10 increase in HBV DNA from nadir. Two consecutive visits that met the definition were required for a participant to be classified as having had virologic breakthrough.

  18. Number of Participants With Drug-Resistance Mutations at Week 48 or at the Last Visit Available [ Time Frame: Baseline to Week 48 ]
    Resistance surveillance analysis was conducted at Week 48 or Early Discontinuation (with at least 24 weeks of exposure to TDF) for any participants who met inclusion criteria (HBV DNA ≥ 69 IU/mL). Drug-resistant mutation status was assessed using HBV polymerase/ reverse transcriptase (pol/RT) population sequencing.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study
  • Documented evidence of chronic hepatitis B virus (HBV) infection, for example, hepatitis B surface antigen (HBsAg) positive for more than 6 months
  • Screening HBV DNA ≥ 2000 IU/mL
  • A negative serum pregnancy test is required for females (unless surgically sterile or > 2 years post-menopausal)

Key Exclusion Criteria:

  • Cirrhosis
  • Inadequate liver function
  • Co-infection with hepatitis C virus (HCV), HIV or hepatitis D virus (HDV)
  • Received antiviral treatment for HBV within 3 months of screening
  • Evidence of hepatocellular carcinoma (eg, as evidenced by recent imaging)
  • Significant cardiovascular, pulmonary, or neurological disease
  • Women who are pregnant or may wish to become pregnant during the course of the study
  • Received solid organ or bone marrow transplant
  • Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, interferon) within 3 months of screening
  • Use of investigational agents within 3 months of screening
  • Current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance
  • Receipt of immunoglobulin or other blood products within 3 months prior to enrollment
  • History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease, Ulcerative colitis, or autoimmune disease
  • Documented history of yeast allergy
  • Known hypersensitivity to study drugs, 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). Individuals under evaluation for possible malignancy are not eligible

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02174276


Locations
Show Show 33 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
Publications of Results:
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02174276    
Other Study ID Numbers: GS-US-330-1401
2014-001011-39 ( EudraCT Number )
First Posted: June 25, 2014    Key Record Dates
Results First Posted: June 4, 2019
Last Update Posted: June 4, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents