Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    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

    Summary
    EudraCT number
    		 2015-002017-30
    Trial protocol
    		 GB  
    Global end of trial date
    03 May 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 May 2020
    First version publication date
    17 May 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GS-US-283-1062
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02579382
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 May 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Jan 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    03 May 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of this study were to evaluate the safety, tolerability, and efficacy of vesatolimod (formerly GS-9620) in adults with chronic hepatitis B (CHB) infection who were currently not being treated.
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Nov 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 12
    Country: Number of subjects enrolled
    Korea, Republic of: 51
    Country: Number of subjects enrolled
    United States: 43
    Country: Number of subjects enrolled
    Italy: 32
    Country: Number of subjects enrolled
    Canada: 23
    Country: Number of subjects enrolled
    Taiwan: 21
    Country: Number of subjects enrolled
    Hong Kong: 5
    Country: Number of subjects enrolled
    New Zealand: 5
    Worldwide total number of subjects
    192
    EEA total number of subjects
    44
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    191
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled at study sites in Asia, Europe, New Zealand, and North America. The first participant was screened on 10 November 2015. The last study visit occurred on 03 May 2019.

    Pre-assignment
    Screening details
    		 260 participants were screened.

    Period 1
    Period 1 title
    Main Study Phase
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 TDF + Placebo
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TDF
    Investigational medicinal product code
    Other name
    Viread
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg administered orally once daily

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo administered orally once a week (every 7 days) for 12 doses

    Arm title
    		 TDF + Vesatolimod 1 mg
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TDF
    Investigational medicinal product code
    Other name
    Viread
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg administered orally once daily

    Investigational medicinal product name
    Vesatolimod
    Investigational medicinal product code
    Other name
    GS-9620
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg orally once a week (every 7 days) for 12 doses

    Arm title
    		 TDF + Vesatolimod 2 mg
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TDF
    Investigational medicinal product code
    Other name
    Viread
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg administered orally once daily

    Investigational medicinal product name
    Vesatolimod
    Investigational medicinal product code
    Other name
    GS-9620
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2 mg orally once a week (every 7 days) for 12 doses

    Arm title
    		 TDF + Vesatolimod 4 mg
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TDF
    Investigational medicinal product code
    Other name
    Viread
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg administered orally once daily

    Investigational medicinal product name
    Vesatolimod
    Investigational medicinal product code
    Other name
    GS-9620
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg orally once a week (every 7 days) for 12 doses

    Number of subjects in period 1
    		TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Started
    28
    53
    56
    55
    Completed
    28
    53
    54
    52
    Not completed
    0
    0
    2
    3
         Lost to follow-up
    -
    -
    2
    -
         Withdrew consent
    -
    -
    -
    2
         Lack of efficacy
    -
    -
    -
    1
    Period 2
    Period 2 title
    Optional Treatment Extension Phase
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OTEP: TDF Extension from TDF + Placebo
    Arm description
    		 Optional Treatment Extension Phase (OTEP): At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TDF
    Investigational medicinal product code
    Other name
    Viread
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg administered orally once daily

    Arm title
    		 OTEP: TDF Extension from TDF + Vesatolimod 1 mg
    Arm description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TDF
    Investigational medicinal product code
    Other name
    Viread
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg administered orally once daily

    Arm title
    		 OTEP: TDF Extension from TDF + Vesatolimod 2 mg
    Arm description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TDF
    Investigational medicinal product code
    Other name
    Viread
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg administered orally once daily

    Arm title
    		 OTEP: TDF Extension from TDF + Vesatolimod 4 mg
    Arm description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TDF
    Investigational medicinal product code
    Other name
    Viread
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg administered orally once daily

    Number of subjects in period 2 [1]
    		OTEP: TDF Extension from TDF + Placebo OTEP: TDF Extension from TDF + Vesatolimod 1 mg OTEP: TDF Extension from TDF + Vesatolimod 2 mg OTEP: TDF Extension from TDF + Vesatolimod 4 mg
    Started
    27
    51
    54
    49
    Completed
    26
    44
    50
    44
    Not completed
    1
    7
    4
    5
         Non-compliance with Study Drug
    -
    1
    -
    -
         Pregnancy
    -
    1
    -
    -
         Adverse event
    -
    1
    -
    -
         Investigator's discretion
    1
    -
    2
    -
         Lost to follow-up
    -
    1
    1
    1
         Withdrew consent
    -
    3
    1
    4
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Participants in the following arms completed the Main Study Phase but did not enter the OTEP: TDF Extension From TDF + Placebo: N = 1; TDF Extension From TDF + Vesatolimod 1 mg: N = 2 ; TDF Extension From TDF + Vesatolimod 4 mg: N = 3.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    TDF + Placebo
    Reporting group description
    		 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.

    Reporting group title
    TDF + Vesatolimod 1 mg
    Reporting group description
    		 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.

    Reporting group title
    TDF + Vesatolimod 2 mg
    Reporting group description
    		 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.

    Reporting group title
    TDF + Vesatolimod 4 mg
    Reporting group description
    		 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.

    Reporting group values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg Total
    Number of subjects
    		 28 53 56 55 192
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 41 ( 10.4 ) 41 ( 9.6 ) 44 ( 10.3 ) 44 ( 10.3 ) -
    Gender categorical
    Units: Subjects
        Female
    		 12 21 16 20 69
        Male
    		 16 32 40 35 123
    Race
    Units: Subjects
        Asian
    		 22 41 48 44 155
        White
    		 4 6 5 10 25
        Black or African American
    		 1 5 3 0 9
        Native Hawaiian or Pacific Islander
    		 1 0 0 1 2
        Other
    		 0 1 0 0 1
    Ethnicity
    Not Permitted = local regulators did not allow collection of race or ethnicity information.
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0 0
        Not Hispanic or Latino
    		 28 53 56 55 192
        Not Permitted
    		 0 0 0 0 0
    Hepatitis B Envelope Antigen (HBeAg) Status
    Units: Subjects
        HBeAg Status- Negative
    		 17 33 33 34 117
        HBeAg Status- Positive
    		 11 20 23 21 75
    Serum Hepatitis B Surface Antigen (HBsAg) (log10 IU/ mL)
    Units: log10 IU/mL
        arithmetic mean (standard deviation)
    		 3.8 ( 0.84 ) 3.7 ( 0.84 ) 3.5 ( 0.88 ) 3.6 ( 0.74 ) -
    Hepatitis B Virus (HBV) DNA
    Units: log10 IU/mL
        arithmetic mean (standard deviation)
    		 5.9 ( 2.10 ) 5.9 ( 1.80 ) 5.6 ( 1.85 ) 5.9 ( 1.70 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    TDF + Placebo
    Reporting group description
    		 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.

    Reporting group title
    TDF + Vesatolimod 1 mg
    Reporting group description
    		 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.

    Reporting group title
    TDF + Vesatolimod 2 mg
    Reporting group description
    		 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.

    Reporting group title
    TDF + Vesatolimod 4 mg
    Reporting group description
    		 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.
    Reporting group title
    OTEP: TDF Extension from TDF + Placebo
    Reporting group description
    		 Optional Treatment Extension Phase (OTEP): At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.

    Reporting group title
    OTEP: TDF Extension from TDF + Vesatolimod 1 mg
    Reporting group description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.

    Reporting group title
    OTEP: TDF Extension from TDF + Vesatolimod 2 mg
    Reporting group description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.

    Reporting group title
    OTEP: TDF Extension from TDF + Vesatolimod 4 mg
    Reporting group description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.

    Primary: Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) from Baseline at Week 24

    		 Close Top of page
    End point title
    		 Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) from Baseline at Week 24
    End point description
    The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analysed 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. The Full Analysis Set included all participants who were randomised and took at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Baseline; Week 24
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    54
    54
    Units: IU/mL
        least squares mean (confidence interval 95%)
    -0.163 (-0.305 to -0.022)
    -0.056 (-0.159 to 0.047)
    -0.146 (-0.246 to -0.045)
    -0.036 (-0.138 to 0.065)
    Statistical analysis title
    		 TDF + Vesatolimod 1 mg vs TDF + Placebo
    Comparison groups
    TDF + Placebo v TDF + Vesatolimod 1 mg
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.227 [1]
    Method
    		 MMRM
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.107
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.067
         upper limit
    		 0.282
    Notes
    [1] - MMRM model included treatment, baseline ALT level, HBeAg baseline status, baseline HBsAg, visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.
    Statistical analysis title
    		 TDF + Vesatolimod 2 mg vs TDF + Placebo
    Comparison groups
    TDF + Placebo v TDF + Vesatolimod 2 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.84 [2]
    Method
    		 MMRM
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.018
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.156
         upper limit
    		 0.191
    Notes
    [2] - MMRM model included treatment, baseline ALT level, HBeAg baseline status, baseline HBsAg, visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.
    Statistical analysis title
    		 TDF + Vesatolimod 4 mg vs TDF + Placebo
    Comparison groups
    TDF + Placebo v TDF + Vesatolimod 4 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.151 [3]
    Method
    		 MMRM
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.127
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.047
         upper limit
    		 0.301
    Notes
    [3] - MMRM model included treatment, baseline ALT level, HBeAg baseline status, baseline HBsAg, visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.

    Secondary: Percentage of Participants With HBeAg Loss and Seroconversion at Week 24

    		 Close Top of page
    End point title
    		 Percentage of Participants With HBeAg Loss and Seroconversion at Week 24
    End point description
    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. Participants in the Full Analysis Set who were HBeAg positive at baseline were analysed.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    11
    20
    23
    21
    Units: percentage of participants
        number (not applicable)
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With HBeAg Loss and Seroconversion at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants With HBeAg Loss and Seroconversion at Week 48
    End point description
    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. Participants in the Full Analysis Set who were HBeAg positive at baseline were analysed.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    11
    20
    23
    21
    Units: percentage of participants
        number (not applicable)
    0
    5.0
    4.3
    4.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants with HBsAg Loss and Seroconversion at Week 24

    		 Close Top of page
    End point title
    		 Percentage of Participants with HBsAg Loss and Seroconversion at Week 24
    End point description
    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. Participants in the Full Analysis Set who were HBsAg positive at baseline were analysed.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    56
    55
    Units: percentage of participants
        number (not applicable)
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with HBsAg Loss and Seroconversion at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants with HBsAg Loss and Seroconversion at Week 48
    End point description
    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. Participants in the Full Analysis Set who were HBsAg positive at baseline were analysed.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    56
    55
    Units: percentage of participants
        number (not applicable)
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Mean Change (Measured in log10 IU/mL) in HBsAg from Baseline at Week 12

    		 Close Top of page
    End point title
    		 Mean Change (Measured in log10 IU/mL) in HBsAg from Baseline at Week 12
    End point description
    Participants in the Full Analysis Set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 12
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    27
    53
    55
    52
    Units: log10 IU/mL
        arithmetic mean (standard deviation)
    -0.087 ( 0.2199 )
    -0.041 ( 0.2283 )
    -0.138 ( 0.5247 )
    -0.020 ( 0.2668 )
    No statistical analyses for this end point

    Secondary: Mean Change (Measured in log10 IU/mL) in HBsAg from Baseline at Week 48

    		 Close Top of page
    End point title
    		 Mean Change (Measured in log10 IU/mL) in HBsAg from Baseline at Week 48
    End point description
    Participants in the Full Analysis Set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 48
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    54
    53
    Units: log10 IU/mL
        arithmetic mean (standard deviation)
    -0.338 ( 0.8922 )
    -0.079 ( 0.2912 )
    -0.197 ( 0.5757 )
    -0.088 ( 0.3700 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers from Baseline at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants with a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers from Baseline at Week 12
    End point description
    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. Participants in the Full Analysis Set were analysed. Missing values were considered failures.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    56
    55
    Units: percentage of participants
        number (not applicable)
    7.1
    3.8
    10.7
    1.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers from Baseline at Week 24

    		 Close Top of page
    End point title
    		 Percentage of Participants with a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers from Baseline at Week 24
    End point description
    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. Participants in the Full Analysis Set were analysed. Missing values were considered failures.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    56
    55
    Units: percentage of participants
        number (not applicable)
    10.7
    3.8
    10.7
    3.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers from Baseline at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants with a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers from Baseline at Week 48
    End point description
    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. Participants in the Full Analysis Set were analysed. Missing values were considered failures.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 48
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    56
    55
    Units: percentage of participants
        number (not applicable)
    17.9
    5.7
    16.1
    14.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24

    		 Close Top of page
    End point title
    		 Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24
    End point description
    LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis. Participants in the Full Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    56
    55
    Units: percentage of participants
        number (not applicable)
    53.6
    58.5
    59.3
    63.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With HBV DNA < LLOQ at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants With HBV DNA < LLOQ at Week 48
    End point description
    LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis. Participants in the Full Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    56
    55
    Units: percentage of participants
        number (not applicable)
    64.3
    62.3
    75.9
    75.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants Experiencing Virologic Breakthrough

    		 Close Top of page
    End point title
    		 Percentage of Participants Experiencing Virologic Breakthrough
    End point description
    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. Participants in the Full Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Weeks 24 and 48
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    28
    53
    56
    55
    Units: percentage of participants
    number (not applicable)
        Week 24
    0
    0
    1.8
    0
        Week 48
    0
    3.8
    1.8
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/reverse transcriptase (pol/RT)

    		 Close Top of page
    End point title
    		 Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/reverse transcriptase (pol/RT)
    End point description
    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. Participants in the Full Analysis Set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 48
    End point values
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    13
    5
    7
    Units: participants
    2
    4
    2
    2
    No statistical analyses for this end point

    Secondary: Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod

    		 Close Top of page
    End point title
    		 Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod [4]
    End point description
    AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration. The PK Substudy Analysis Set included all randomised participants who took at least 1 dose of vesatolimod, participated in the PK substudy, and had at least 1 non-missing steady state PK parameter.
    End point type
    Secondary
    End point timeframe
    Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: hours*picogram/milliliter (h*pg/mL)
        arithmetic mean (standard deviation)
    5252.3 ( 5756.26 )
    7170.6 ( 4569.83 )
    28537.2 ( 23608.94 )
    No statistical analyses for this end point

    Secondary: PK Parameter: AUCinf of Vesatolimod

    		 Close Top of page
    End point title
    		 PK Parameter: AUCinf of Vesatolimod [5]
    End point description
    AUCinf is defined as the concentration of drug extrapolated to infinite time. Participants in the PK Substudy Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: h*pg/mL
        arithmetic mean (standard deviation)
    7277.3 ( 6550.71 )
    10239.0 ( 6243.75 )
    34534.8 ( 26482.89 )
    No statistical analyses for this end point

    Secondary: PK Parameter: %AUCexp of Vesatolimod

    		 Close Top of page
    End point title
    		 PK Parameter: %AUCexp of Vesatolimod [6]
    End point description
    %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. Participants in the PK Substudy Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: percentage
        arithmetic mean (standard deviation)
    31.1 ( 19.70 )
    28.61 ( 11.42 )
    19.3 ( 6.15 )
    No statistical analyses for this end point

    Secondary: PK Parameter: Cmax of Vesatolimod

    		 Close Top of page
    End point title
    		 PK Parameter: Cmax of Vesatolimod [7]
    End point description
    Cmax is defined as the maximum concentration of drug. Participants in the PK Substudy Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: pg/mL
        arithmetic mean (standard deviation)
    667.8 ( 785.44 )
    850.4 ( 569.75 )
    4957.5 ( 5035.46 )
    No statistical analyses for this end point

    Secondary: PK Parameter: Clast of Vesatolimod

    		 Close Top of page
    End point title
    		 PK Parameter: Clast of Vesatolimod [8]
    End point description
    Clast is defined as the last observable concentration of drug. Participants in the PK Substudy Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: pg/mL
        arithmetic mean (standard deviation)
    92.8 ( 73.80 )
    119.0 ( 74.45 )
    328.0 ( 165.19 )
    No statistical analyses for this end point

    Secondary: PK Parameter: Tmax of Vesatolimod

    		 Close Top of page
    End point title
    		 PK Parameter: Tmax of Vesatolimod [9]
    End point description
    Tmax is defined as the time (observed time point) of Cmax. Participants in the PK Substudy Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: hour (h)
        median (full range (min-max))
    1.00 (0.47 to 4.00)
    2.00 (2.00 to 4.00)
    3.00 (1.00 to 4.00)
    No statistical analyses for this end point

    Secondary: PK Parameter: Tlast of Vesatolimod

    		 Close Top of page
    End point title
    		 PK Parameter: Tlast of Vesatolimod [10]
    End point description
    Tlast is defined as the time (observed time point) of Clast. Participants in the PK Substudy Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: hour
        median (full range (min-max))
    24.00 (8.00 to 24.00)
    24.00 (24.00 to 24.00)
    24.00 (24.00 to 24.00)
    No statistical analyses for this end point

    Secondary: PK Parameter: T1/2 of Vesatolimod

    		 Close Top of page
    End point title
    		 PK Parameter: T1/2 of Vesatolimod [11]
    End point description
    T1/2 is defined as the estimate of the terminal elimination half-life of the drug. Participants in the PK Substudy Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: hour
        median (full range (min-max))
    10.79 (4.57 to 50.08)
    14.12 (12.32 to 26.49)
    13.32 (8.90 to 14.83)
    No statistical analyses for this end point

    Secondary: PK Parameter: CL/F of Vesatolimod

    		 Close Top of page
    End point title
    		 PK Parameter: CL/F of Vesatolimod [12]
    End point description
    CL/F is defined as the apparent oral clearance following administration of the drug. Participants in the PK Substudy Analysis Set were analysed.
    End point type
    Secondary
    End point timeframe
    Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics of study drug Vesatolimod was performed.
    End point values
    		 TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg
    Number of subjects analysed
    5
    5
    4
    Units: liter/hour
        arithmetic mean (standard deviation)
    273.9 ( 270.58 )
    262.3 ( 144.45 )
    156.2 ( 72.48 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    First dose date up to last dose of study drug (Maximum: 144 weeks)
    Adverse event reporting additional description
    The Safety Analysis Set included all participants who took at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    TDF + Placebo
    Reporting group description
    		 Main Study Phase: Placebo administered orally once a week (every 7 days) for 12 doses + tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks.

    Reporting group title
    TDF + Vesatolimod 1 mg
    Reporting group description
    		 Main Study Phase: Vesatolimod (GS 9620) 1 mg tablet orally once a week (every 7 days) for 12 doses + TDF 300 mg tablets orally once daily for up to 48 weeks.

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

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

    Reporting group title
    TDF Extension From TDF + Placebo
    Reporting group description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144; includes participants who received TDF + Placebo in the Main Study Phase.

    Reporting group title
    TDF Extension From TDF + Vesatolimod 1 mg
    Reporting group description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144; includes participants who received TDF + Vesatolimod 1 mg in the Main Study Phase.

    Reporting group title
    TDF Extension From TDF + Vesatolimod 2 mg
    Reporting group description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144; includes participants who received TDF + Vesatolimod 2 mg in the Main Study Phase.

    Reporting group title
    TDF Extension from TDF + Vesatolimod 4 mg
    Reporting group description
    		 Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144; includes participants who received TDF + Vesatolimod 4 mg in the Main Study Phase.

    Serious adverse events
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg TDF Extension From TDF + Placebo TDF Extension From TDF + Vesatolimod 1 mg TDF Extension From TDF + Vesatolimod 2 mg TDF Extension from TDF + Vesatolimod 4 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 53 (1.89%)
    1 / 56 (1.79%)
    1 / 55 (1.82%)
    1 / 27 (3.70%)
    4 / 51 (7.84%)
    5 / 54 (9.26%)
    1 / 49 (2.04%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    2 / 51 (3.92%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    1 / 51 (1.96%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leiomyoma
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    1 / 27 (3.70%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Skin laceration
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 53 (1.89%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Facial paralysis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    1 / 55 (1.82%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adenomyosis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    1 / 51 (1.96%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic congestion
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    1 / 27 (3.70%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 53 (0.00%)
    1 / 56 (1.79%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 TDF + Placebo TDF + Vesatolimod 1 mg TDF + Vesatolimod 2 mg TDF + Vesatolimod 4 mg TDF Extension From TDF + Placebo TDF Extension From TDF + Vesatolimod 1 mg TDF Extension From TDF + Vesatolimod 2 mg TDF Extension from TDF + Vesatolimod 4 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 28 (50.00%)
    25 / 53 (47.17%)
    27 / 56 (48.21%)
    33 / 55 (60.00%)
    7 / 27 (25.93%)
    14 / 51 (27.45%)
    13 / 54 (24.07%)
    12 / 49 (24.49%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 28 (17.86%)
    4 / 53 (7.55%)
    10 / 56 (17.86%)
    12 / 55 (21.82%)
    0 / 27 (0.00%)
    2 / 51 (3.92%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    7
    6
    25
    18
    0
    2
    0
    1
    Dizziness
         subjects affected / exposed
    3 / 28 (10.71%)
    3 / 53 (5.66%)
    1 / 56 (1.79%)
    5 / 55 (9.09%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    3
    4
    1
    6
    0
    0
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    6 / 28 (21.43%)
    8 / 53 (15.09%)
    6 / 56 (10.71%)
    14 / 55 (25.45%)
    0 / 27 (0.00%)
    2 / 51 (3.92%)
    1 / 54 (1.85%)
    2 / 49 (4.08%)
         occurrences all number
    7
    17
    6
    18
    0
    2
    1
    2
    Pyrexia
         subjects affected / exposed
    1 / 28 (3.57%)
    4 / 53 (7.55%)
    5 / 56 (8.93%)
    11 / 55 (20.00%)
    0 / 27 (0.00%)
    2 / 51 (3.92%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    1
    5
    8
    18
    0
    2
    0
    0
    Chills
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 53 (3.77%)
    6 / 56 (10.71%)
    10 / 55 (18.18%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences all number
    1
    2
    22
    13
    0
    0
    1
    0
    Asthenia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 53 (1.89%)
    2 / 56 (3.57%)
    3 / 55 (5.45%)
    0 / 27 (0.00%)
    1 / 51 (1.96%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    2
    1
    7
    12
    0
    1
    0
    0
    Influenza like illness
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 53 (1.89%)
    0 / 56 (0.00%)
    5 / 55 (9.09%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    1
    0
    13
    0
    0
    0
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    3 / 28 (10.71%)
    5 / 53 (9.43%)
    3 / 56 (5.36%)
    5 / 55 (9.09%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    2 / 54 (3.70%)
    0 / 49 (0.00%)
         occurrences all number
    5
    7
    4
    6
    0
    0
    2
    0
    Diarrhoea
         subjects affected / exposed
    0 / 28 (0.00%)
    4 / 53 (7.55%)
    2 / 56 (3.57%)
    5 / 55 (9.09%)
    0 / 27 (0.00%)
    1 / 51 (1.96%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
         occurrences all number
    0
    4
    3
    6
    0
    1
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    2 / 28 (7.14%)
    3 / 53 (5.66%)
    1 / 56 (1.79%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    2 / 51 (3.92%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
         occurrences all number
    3
    3
    1
    0
    0
    2
    1
    1
    Dyspepsia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 53 (1.89%)
    3 / 56 (5.36%)
    1 / 55 (1.82%)
    1 / 27 (3.70%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
         occurrences all number
    4
    1
    3
    1
    1
    0
    2
    1
    Abdominal distension
         subjects affected / exposed
    2 / 28 (7.14%)
    3 / 53 (5.66%)
    1 / 56 (1.79%)
    1 / 55 (1.82%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    2
    3
    1
    1
    0
    0
    0
    2
    Vomiting
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 53 (3.77%)
    0 / 56 (0.00%)
    5 / 55 (9.09%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    2
    0
    5
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 28 (0.00%)
    3 / 53 (5.66%)
    0 / 56 (0.00%)
    2 / 55 (3.64%)
    2 / 27 (7.41%)
    2 / 51 (3.92%)
    1 / 54 (1.85%)
    3 / 49 (6.12%)
         occurrences all number
    0
    4
    0
    3
    2
    2
    2
    3
    Oropharyngeal pain
         subjects affected / exposed
    1 / 28 (3.57%)
    5 / 53 (9.43%)
    1 / 56 (1.79%)
    1 / 55 (1.82%)
    1 / 27 (3.70%)
    0 / 51 (0.00%)
    2 / 54 (3.70%)
    0 / 49 (0.00%)
         occurrences all number
    1
    7
    1
    1
    1
    0
    2
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 28 (0.00%)
    3 / 53 (5.66%)
    1 / 56 (1.79%)
    2 / 55 (3.64%)
    1 / 27 (3.70%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    3
    1
    2
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    3 / 28 (10.71%)
    5 / 53 (9.43%)
    4 / 56 (7.14%)
    9 / 55 (16.36%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    3
    6
    7
    25
    0
    0
    0
    0
    Arthralgia
         subjects affected / exposed
    0 / 28 (0.00%)
    3 / 53 (5.66%)
    3 / 56 (5.36%)
    10 / 55 (18.18%)
    0 / 27 (0.00%)
    2 / 51 (3.92%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    4
    3
    22
    0
    2
    0
    0
    Back pain
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 53 (3.77%)
    4 / 56 (7.14%)
    2 / 55 (3.64%)
    2 / 27 (7.41%)
    2 / 51 (3.92%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    2
    4
    2
    2
    2
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 53 (3.77%)
    3 / 56 (5.36%)
    1 / 55 (1.82%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    2
    4
    1
    0
    0
    0
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 28 (10.71%)
    3 / 53 (5.66%)
    0 / 56 (0.00%)
    4 / 55 (7.27%)
    2 / 27 (7.41%)
    3 / 51 (5.88%)
    4 / 54 (7.41%)
    2 / 49 (4.08%)
         occurrences all number
    5
    3
    0
    5
    3
    12
    5
    5
    Nasopharyngitis
         subjects affected / exposed
    3 / 28 (10.71%)
    2 / 53 (3.77%)
    2 / 56 (3.57%)
    1 / 55 (1.82%)
    0 / 27 (0.00%)
    5 / 51 (9.80%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
         occurrences all number
    4
    2
    2
    2
    0
    6
    1
    1
    Gingivitis
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 53 (0.00%)
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 27 (0.00%)
    1 / 51 (1.96%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 53 (1.89%)
    3 / 56 (5.36%)
    1 / 55 (1.82%)
    0 / 27 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    1
    1
    3
    1
    0
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Sep 2015
    1. References to peripheral blood mononuclear cell (PBMC) collection and associated objectives, endpoints, analysis, and storage were removed. These changes were implemented to reflect that PBMC collection would not be completed in certain countries. The original protocol (dated 21 August 2015) was applicable in countries where PBMCs were collected, and this Original 0.1 protocol was applicable in countries where PBMCs were not collected. 2. The definition of “treatment-emergent” was changed from “30 days from the last dose of study drug” to “the date of the last dose of study drug.” This change was implemented to account for the treatment-free follow-up phase that began immediately after the last dose of study drug.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/29851204
    http://www.ncbi.nlm.nih.gov/pubmed/29505905
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 18 14:26:58 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA