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Study to Evaluate the Safety, Tolerability, and Efficacy of Vesatolimod in Combination With Tenofovir Disoproxil Fumarate (TDF) in Adults With Chronic Hepatitis B (CHB) Infection Who Are Currently Not Being Treated

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ClinicalTrials.gov Identifier: NCT02579382
Recruitment Status : Completed
First Posted : October 19, 2015
Results First Posted : May 18, 2020
Last Update Posted : May 18, 2020
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 vesatolimod (formerly GS-9620) in adults with chronic hepatitis B (CHB) infection who are currently not being treated.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: TDF Drug: Vesatolimod Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 192 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 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 : November 10, 2015
Actual Primary Completion Date : January 16, 2017
Actual Study Completion Date : May 3, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: TDF + placebo

Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses.

Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.

Drug: TDF
300 mg tablets administered orally once daily
Other Name: Viread®

Drug: Placebo
Placebo administered orally once a week (every 7 days) for 12 doses

Experimental: TDF + Vesatolimod 1 mg

Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses.

Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.

Drug: TDF
300 mg tablets administered orally once daily
Other Name: Viread®

Drug: Vesatolimod
Tablets administered orally once a week (every 7 days) for 12 doses
Other Name: GS-9620

Experimental: TDF + Vesatolimod 2 mg

Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses.

Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.

Drug: TDF
300 mg tablets administered orally once daily
Other Name: Viread®

Drug: Vesatolimod
Tablets administered orally once a week (every 7 days) for 12 doses
Other Name: GS-9620

Experimental: TDF + Vesatolimod 4 mg

Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses.

Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.

Drug: TDF
300 mg tablets administered orally once daily
Other Name: Viread®

Drug: Vesatolimod
Tablets administered orally once a week (every 7 days) for 12 doses
Other Name: GS-9620




Primary Outcome Measures :
  1. Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24 [ Time Frame: Baseline; Week 24 ]
    The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analyzed using a mixed model for repeated measures (MMRM). The model included treatment, baseline HBsAg (log10 IU/mL), baseline Hepatitis B Envelope Antigen (HBeAg) status (positive or negative), baseline alanine aminotransferase (ALT) level relative to upper limit of normal (ULN) (> 19 vs ≤ 19 IU/L for females; > 30 vs ≤ 30 IU/L for males), visit and treatment-by-visit interaction as fixed effects, and visit as a repeated measure.


Secondary Outcome Measures :
  1. Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 [ Time Frame: Week 24 ]
    HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative Hepatitis B Envelope Antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.

  2. Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 [ Time Frame: Week 48 ]
    HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.

  3. Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 [ Time Frame: Week 24 ]
    HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative Hepatitis B Surface Antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.

  4. Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 [ Time Frame: Week 48 ]
    HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.

  5. Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12 [ Time Frame: Baseline; Week 12 ]
  6. Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48 [ Time Frame: Baseline; Week 48 ]
  7. Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12 [ Time Frame: Baseline to Week 12 ]
    HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.

  8. Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24 [ Time Frame: Baseline to Week 24 ]
    HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 24 post-baseline visit.

  9. Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48 [ Time Frame: Baseline to Week 48 ]
    HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.

  10. Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24 [ Time Frame: Week 24 ]
    LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.

  11. Percentage of Participants With HBV DNA < LLOQ at Week 48 [ Time Frame: Week 48 ]
    LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.

  12. Percentage of Participants Experiencing Virologic Breakthrough [ Time Frame: Weeks 24 and 48 ]
    Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having had HBV DNA < 69 IU/mL or confirmed 1.0 log10 IU/mL or greater increase in HBV DNA from nadir. Confirmation requires 2 consecutive occurrences of elevation in HBV DNA to > 69 IU/mL after having had HBV DNA < 69 IU/mL or 1.0 log10 IU/mL or greater increases in HBV DNA from nadir.

  13. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT) [ Time Frame: Baseline; Week 48 ]
    Sequence analysis of the HBV pol/RT was attempted for any participant who had HBV DNA ≥ 69 IU/mL at Week 48 or early discontinuation. Results of the alignment of Week 48 and baseline sequence were reported as a change from baseline sequence.

  14. Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.

  15. PK Parameter: AUCinf of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    AUCinf is defined as the concentration of drug extrapolated to infinite time.

  16. PK Parameter: %AUCexp of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.

  17. PK Parameter: Cmax of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    Cmax is defined as the maximum concentration of drug.

  18. PK Parameter: Clast of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    Clast is defined as the last observable concentration of drug.

  19. PK Parameter: Tmax of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    Tmax is defined as the time (observed time point) of Cmax

  20. PK Parameter: Tlast of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    Tlast is defined as the time (observed time point) of Clast.

  21. PK Parameter: T1/2 of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    T1/2 is defined as the estimate of the terminal elimination half-life of the drug.

  22. PK Parameter: CL/F of Vesatolimod [ Time Frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose ]
    CL/F is defined as the apparent oral clearance following administration of the drug.



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 to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Adult males or females between the ages of 18-65
  • Chronic hepatitis B virus (HBV) infection
  • HBV deoxyribonucleic acid (DNA ) ≥ 2000 IU/mL at screening

Key Exclusion Criteria:

  • Extensive bridging fibrosis or cirrhosis
  • Received oral antiviral treatment for HBV or prolonged therapy with immune-modulators or biologics within 3 months of screening
  • Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV) or hepatitis D virus (HDV)
  • Chronic liver disease other than HBV
  • Lactating or pregnant females or those that wish to become pregnant during the course of the study

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): NCT02579382


Locations
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United States, California
Los Angeles, California, United States
Palo Alto, California, United States
San Diego, California, United States
San Francisco, California, United States
United States, Hawaii
Honolulu, Hawaii, United States
United States, Maryland
Catonsville, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, New York
Flushing, New York, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Canada, Ontario
Toronto, Ontario, Canada
Hong Kong
Kowloon, Hong Kong
Italy
Bologna, Italy
Milano, Italy
Pisa, Italy
San Giovanni Rotondo, Italy
Korea, Republic of
Daegu, Korea, Republic of
Seoul, Korea, Republic of
New Zealand
Grafton, Auckland, New Zealand
Taiwan
Dalin, Taiwan
Kaohsiung, Taiwan
United Kingdom
London, United Kingdom
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
Publications of Results:
Agarwal K, Ahn SH, Elkhashab M, Kim K, Lau AH, Gaggar A, et al. Safety and efficacy ofvesatolimod (GS-9620) in patients with chronic hepatitis B (CHB) who are not currently on antiviral treatment. Poster 930. AASLD 2017. Hepatology; 66:497A 498A, 2017.
Younossi ZM, Stepanova M, Janssen H, Agarwal K, Nguyen MH, Gane EJ, et al. The impact of treatment of chronic hepatitis B (CHB) on patient reported outcomes (PROs). Poster 1924. AASLD 2017. Hepatology; 66:1020A, 2017.
Lau A, Joshi A, Nguyen AH, Gaggar A, Patterson SD, Woo J. Peripheral blood immune cell profiling in virally suppressed chronic hepatitis B (CHB) patients and CHB patients not on an oral antiviral therapy. HBV International Meeting 2017.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02579382    
Other Study ID Numbers: GS-US-283-1062
2015-002017-30 ( EudraCT Number )
First Posted: October 19, 2015    Key Record Dates
Results First Posted: May 18, 2020
Last Update Posted: May 18, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
HBV
Hepatitis
Liver Disease
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
Vesatolimod
Antiviral Agents
Anti-Infective Agents