Clincosm LogoSign in Get a demo

Study To Evaluate Safety and Efficacy of Vesatolimod for the Treatment of Chronic Hepatitis B Virus in Virally-Suppressed Participants

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02166047
Collaborator
(none)
162
Enrollment
23
Locations
12
Arms
27.7
Actual Duration (Months)
7
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod in participants with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV).

Participants will be randomized in 3 sequential cohorts (Cohorts A, B, and C). Within each cohort, participants will be randomized in a 1:3:3:3 ratio to placebo or one of the doses of vesatolimod (1, 2, or 4 mg).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
162 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Double (Participant, Care Provider)
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 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B
Actual Study Start Date :
Jun 30, 2014
Actual Primary Completion Date :
May 11, 2016
Actual Study Completion Date :
Oct 20, 2016

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo 4 Weeks (Cohort A)

Placebo tablet once a week for 4 weeks

Drug: Placebo
Placebo to match vesatolimod tablet administered orally
Experimental: Vesatolimod 1 mg 4 Weeks (Cohort A)

Vesatolimod 1 mg tablet once a week for 4 weeks

Drug: Vesatolimod
Vesatolimod tablet administered orally
Other Names:
  • GS-9620

    		•
    Experimental: Vesatolimod 2 mg 4 Weeks (Cohort A)

    Vesatolimod 2 mg tablet once a week for 4 weeks

    Drug: Vesatolimod
    Vesatolimod tablet administered orally
    Other Names:
  • GS-9620

    		•
    Experimental: Vesatolimod 4 mg 4 Weeks (Cohort A)

    Vesatolimod 4 mg tablet once a week for 4 weeks

    Drug: Vesatolimod
    Vesatolimod tablet administered orally
    Other Names:
  • GS-9620

    		•
    Placebo Comparator: Placebo 8 Weeks (Cohort B)

    Placebo tablet once a week for 8 weeks

    Drug: Placebo
    Placebo to match vesatolimod tablet administered orally
    Experimental: Vesatolimod 1 mg 8 Weeks (Cohort B)

    Vesatolimod 1 mg tablet once a week for 8 weeks

    Drug: Vesatolimod
    Vesatolimod tablet administered orally
    Other Names:
  • GS-9620

    		•
    Experimental: Vesatolimod 2 mg 8 Weeks (Cohort B)

    Vesatolimod 2 mg tablet once a week for 8 weeks

    Drug: Vesatolimod
    Vesatolimod tablet administered orally
    Other Names:
  • GS-9620

    		•
    Experimental: Vesatolimod 4 mg 8 Weeks (Cohort B)

    Vesatolimod 4 mg tablet once a week for 8 weeks

    Drug: Vesatolimod
    Vesatolimod tablet administered orally
    Other Names:
  • GS-9620

    		•
    Placebo Comparator: Placebo 12 Weeks (Cohort C)

    Placebo tablet once a week for 12 weeks

    Drug: Placebo
    Placebo to match vesatolimod tablet administered orally
    Experimental: Vesatolimod 1 mg 12 Weeks (Cohort C)

    Vesatolimod 1 mg tablet once a week for 12 weeks

    Drug: Vesatolimod
    Vesatolimod tablet administered orally
    Other Names:
  • GS-9620

    		•
    Experimental: Vesatolimod 2 mg 12 Weeks (Cohort C)

    Vesatolimod 2 mg tablet once a week for 12 weeks

    Drug: Vesatolimod
    Vesatolimod tablet administered orally
    Other Names:
  • GS-9620

    		•
    Experimental: Vesatolimod 4 mg 12 Weeks (Cohort C)

    Vesatolimod 4 mg tablet once a week for 12 weeks

    Drug: Vesatolimod
    Vesatolimod tablet administered orally
    Other Names:
  • GS-9620

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 [Baseline to Week 24]

      A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.

    Secondary Outcome Measures

    1. Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 [Week 24]

      HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.

    2. Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 [Week 48]

      HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. Only participants who were HBeAg+ at baseline were included.

    3. Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 [Week 24]

      HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.

    4. Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 [Week 48]

      HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.

    5. Change From Baseline in Serum HBsAg Level at Week 4 [Baseline; Week 4]

    6. Change From Baseline in Serum HBsAg Level at Week 8 [Baseline; Week 8]

    7. Change From Baseline in Serum HBsAg Level at Week 12 [Baseline; Week 12]

    8. Change From Baseline in Serum HBsAg Level at Week 48 [Baseline; Week 48]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures

    • Documented evidence of CHB infection (eg, hepatitis B surface antigen [HBsAg] positive for more than 6 months) with detectable HBsAg levels at screening

    • Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below lower limit of quantitation (LLOQ), measured at least once, 6 or more months prior to screening, and HBV DNA < 20 IU/mL at screening

    • Currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine, or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening

    • Willing to provide blood sample for toll-like receptor 7 (TLR-7) and interleukin 28 B (IL28B) single-nucleotide polymorphism (SNP) assessment

    • Must be willing and able to comply with all study requirements

    Key Exclusion Criteria:

    • Extensive bridging fibrosis or cirrhosis

    • Laboratory parameters not within defined thresholds for neutropenia, anemia, thrombocytopenia, leukopenia, or other evidence of inadequate liver function

    • Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)

    • Evidence of hepatocellular carcinoma

    • Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Participants under evaluation for possible malignancy are not eligible.

    • Significant cardiovascular, pulmonary, or neurological disease

    • Any of the following conditions that may worsen in response to interferon (IFN):

    • Autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis)

    • Poorly controlled diabetes mellitus

    • Significant psychiatric disorders

    • Thyroid disorder (unless controlled under treatment)

    • Significant pulmonary diseases (eg, chronic obstructive pulmonary disease)

    • Retinal disease

    • Immunodeficiency disorders

    • Received solid organ or bone marrow transplant

    • Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal Ab, interferon) within 3 months of screening

    • Use of another investigational agents within 3 months of screening

    • Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance

    • Females who are pregnant or may wish to become pregnant during the study

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Los Angeles California United States 90095
    2 San Diego California United States 92154
    3 San Francisco California United States 94118
    4 San Jose California United States 95128
    5 Honolulu Hawaii United States 96734
    6 Boston Massachusetts United States 02111
    7 Boston Massachusetts United States 02215
    8 Detroit Michigan United States 48202
    9 Flushing New York United States 11355
    10 Vancouver British Columbia Canada V5Z 1M9
    11 Winnipeg Manitoba Canada R3E 3P4
    12 Toronto Ontario Canada M5G2C4
    13 Toronto Ontario Canada M5T 2S8
    14 San Giovanni Rotondo FG Italy 71013
    15 Milan Italy 20122
    16 Parma Italy 43126
    17 Pisa Italy 56124
    18 Seoul Korea, Republic of 110-744
    19 Seoul Korea, Republic of 120-752
    20 Seoul Korea, Republic of 135-710
    21 Seoul Korea, Republic of 138-736
    22 Rotterdam Netherlands 3015 CE
    23 Auckland New Zealand 1142

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02166047
    Other Study ID Numbers:
    • GS-US-283-1059
    • 2014-001400-22
    • ACTRN12614000628640
    First Posted:
    Jun 18, 2014
    Last Update Posted:
    Oct 14, 2020
    Last Verified:
    Sep 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gilead Sciences
    Hepatitis B
    HBV
    GS-9620
    TLR-7 Agonist
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis B, Chronic
    Hepatitis
    Hepatitis, Chronic
    Vesatolimod

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in the United States, Canada, Italy, South Korea, The Netherlands, and New Zealand. The first participant was screened on 30 June 2014. The last study visit occurred on 20 October 2016.
    Pre-assignment Detail All participants continued their approved HBV oral antiviral therapy (tenofovir disoproxil fumarate (TDF), entecavir (ETV), adefovir, lamivudine, or telbivudine, either as single agents or in combination) throughout the study. 200 participants were screened.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Period Title: Overall Study
    STARTED 16 15 16 5 18 17 17 5 16 17 14 6
    COMPLETED 16 14 14 5 17 17 15 5 16 17 12 6
    NOT COMPLETED 0 1 2 0 1 0 2 0 0 0 2 0

    Baseline Characteristics

    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C) Total
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks Total of all reporting groups
    Overall Participants 16 15 16 5 18 17 17 5 16 17 14 6 162
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    47
    (7.3)
    50
    (11.2)
    47
    (10.0)
    53
    (5.3)
    51
    (8.2)
    44
    (9.0)
    44
    (11.1)
    53
    (5.4)
    48
    (9.8)
    48
    (9.7)
    50
    (11.6)
    46
    (10.9)
    48
    (9.7)
    Sex: Female, Male (Count of Participants)
    Female
    1
    6.3%
    5
    33.3%
    4
    25%
    1
    20%
    9
    50%
    4
    23.5%
    4
    23.5%
    1
    20%
    5
    31.3%
    2
    11.8%
    3
    21.4%
    0
    0%
    39
    24.1%
    Male
    15
    93.8%
    10
    66.7%
    12
    75%
    4
    80%
    9
    50%
    13
    76.5%
    13
    76.5%
    4
    80%
    11
    68.8%
    15
    88.2%
    11
    78.6%
    6
    100%
    123
    75.9%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    13
    81.3%
    10
    66.7%
    12
    75%
    4
    80%
    15
    83.3%
    15
    88.2%
    16
    94.1%
    4
    80%
    9
    56.3%
    8
    47.1%
    9
    64.3%
    2
    33.3%
    117
    72.2%
    Native Hawaiian or Pacific Islander
    1
    6.3%
    2
    13.3%
    3
    18.8%
    0
    0%
    2
    11.1%
    1
    5.9%
    1
    5.9%
    0
    0%
    7
    43.8%
    8
    47.1%
    5
    35.7%
    4
    66.7%
    34
    21%
    White
    2
    12.5%
    1
    6.7%
    1
    6.3%
    1
    20%
    1
    5.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5.9%
    0
    0%
    0
    0%
    7
    4.3%
    Black or African American
    0
    0%
    2
    13.3%
    0
    0%
    0
    0%
    0
    0%
    1
    5.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    1.9%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.6%
    Race/Ethnicity, Customized (Count of Participants)
    Ethnicity: Not Hispanic or Latino
    16
    100%
    15
    100%
    16
    100%
    5
    100%
    18
    100%
    17
    100%
    17
    100%
    5
    100%
    16
    100%
    17
    100%
    14
    100%
    6
    100%
    162
    100%
    Region of Enrollment (Count of Participants)
    Canada
    8
    50%
    3
    20%
    3
    18.8%
    0
    0%
    4
    22.2%
    5
    29.4%
    2
    11.8%
    0
    0%
    2
    12.5%
    2
    11.8%
    2
    14.3%
    2
    33.3%
    33
    20.4%
    Italy
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    56.3%
    8
    47.1%
    9
    64.3%
    2
    33.3%
    28
    17.3%
    Netherlands
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    16.7%
    1
    5.9%
    1
    5.9%
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    6
    3.7%
    New Zealand
    4
    25%
    2
    13.3%
    6
    37.5%
    3
    60%
    1
    5.6%
    3
    17.6%
    0
    0%
    0
    0%
    3
    18.8%
    2
    11.8%
    0
    0%
    0
    0%
    24
    14.8%
    South Korea
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7
    38.9%
    4
    23.5%
    9
    52.9%
    3
    60%
    1
    6.3%
    2
    11.8%
    1
    7.1%
    1
    16.7%
    28
    17.3%
    United States
    4
    25%
    10
    66.7%
    7
    43.8%
    2
    40%
    3
    16.7%
    4
    23.5%
    5
    29.4%
    1
    20%
    1
    6.3%
    3
    17.6%
    2
    14.3%
    1
    16.7%
    43
    26.5%
    Serum Hepatitis B Surface Antigen (HBsAg) Level (log10 IU/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 IU/mL]
    2.8
    (0.88)
    3.1
    (0.59)
    3.0
    (0.70)
    3.1
    (0.69)
    3.1
    (0.62)
    3.0
    (0.69)
    3.1
    (0.90)
    2.7
    (0.73)
    3.3
    (0.45)
    3.0
    (0.54)
    3.0
    (0.69)
    2.4
    (1.01)
    3.0
    (0.70)
    Serum HBsAg Level Categories (Count of Participants)
    ≤ 5000 IU/mL
    13
    81.3%
    13
    86.7%
    13
    81.3%
    4
    80%
    15
    83.3%
    15
    88.2%
    14
    82.4%
    5
    100%
    14
    87.5%
    15
    88.2%
    13
    92.9%
    5
    83.3%
    139
    85.8%
    > 5000 IU/mL
    3
    18.8%
    2
    13.3%
    3
    18.8%
    1
    20%
    3
    16.7%
    2
    11.8%
    3
    17.6%
    0
    0%
    2
    12.5%
    2
    11.8%
    1
    7.1%
    1
    16.7%
    23
    14.2%
    Hepatitis B Envelope Antigen (HBeAg) Status (Count of Participants)
    Negative
    12
    75%
    11
    73.3%
    12
    75%
    4
    80%
    13
    72.2%
    14
    82.4%
    14
    82.4%
    5
    100%
    13
    81.3%
    14
    82.4%
    12
    85.7%
    4
    66.7%
    128
    79%
    Positive
    4
    25%
    4
    26.7%
    4
    25%
    1
    20%
    5
    27.8%
    3
    17.6%
    3
    17.6%
    0
    0%
    3
    18.8%
    3
    17.6%
    2
    14.3%
    2
    33.3%
    34
    21%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24
    Description A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.
    Time Frame Baseline to Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set (participants who were randomized and received at least 1 dose of study drug) with available data were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 16 14 15 5 17 17 16 5 16 17 12 6
    Least Squares Mean (95% Confidence Interval) [log10 IU/mL]
    -0.011
    0.033
    -0.018
    -0.035
    -0.081
    -0.081
    -0.082
    -0.163
    -0.015
    0.000
    0.000
    0.001
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 1 mg 4 Weeks (Cohort A), Placebo 4 Weeks (Cohort A)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.590
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
    Estimated Value 0.023
    Confidence Interval (2-Sided) 95%
    -0.061 to 0.108
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 2 mg 4 Weeks (Cohort A), Placebo 4 Weeks (Cohort A)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.120
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.068
    Confidence Interval (2-Sided) 95%
    -0.018 to 0.154
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg 4 Weeks (Cohort A), Placebo 4 Weeks (Cohort A)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.701
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.017
    Confidence Interval (2-Sided) 95%
    -0.069 to 0.102
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 1 mg 8 Weeks (Cohort B), Placebo 8 Weeks (Cohort B)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.210
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.082
    Confidence Interval (2-Sided) 95%
    -0.046 to 0.210
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 2 mg 8 Weeks (Cohort B), Placebo 8 Weeks (Cohort B)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.207
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.082
    Confidence Interval (2-Sided) 95%
    -0.046 to 0.210
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg 8 Weeks (Cohort B), Placebo 8 Weeks (Cohort B)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.216
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.081
    Confidence Interval (2-Sided) 95%
    -0.048 to 0.210
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 1 mg 12 Weeks (Cohort C), Placebo 12 Weeks (Cohort C)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.652
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.015
    Confidence Interval (2-Sided) 95%
    -0.081 to 0.051
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 2 mg 12 Weeks (Cohort C), Placebo 12 Weeks (Cohort C)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.994
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.000
    Confidence Interval (2-Sided) 95%
    -0.066 to 0.065
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg 12 Weeks (Cohort C), Placebo 12 Weeks (Cohort C)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.996
    Comments P-value between vesatolimod and placebo was not adjusted for multiplicity due to exploratory nature of the study.
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.000
    Confidence Interval (2-Sided) 95%
    -0.069 to 0.069
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24
    Description HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with HBeAg+ at Baseline were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 4 4 4 1 5 3 3 0 3 3 2 2
    Number [percentage of participants]
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    20.0
    111.1%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    3. Secondary Outcome
    Title Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48
    Description HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. Only participants who were HBeAg+ at baseline were included.
    Time Frame Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with HBeAg+ at Baseline were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 4 4 4 1 5 3 3 0 3 3 2 2
    Number [percentage of participants]
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    20.0
    111.1%
    0.0
    0%
    0.0
    0%
    33.3
    666%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    4. Secondary Outcome
    Title Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24
    Description HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 16 15 16 5 18 17 17 5 16 17 14 6
    Number [percentage of participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5. Secondary Outcome
    Title Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48
    Description HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
    Time Frame Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 16 15 16 5 18 17 17 5 16 17 14 6
    Number [percentage of participants]
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    6. Secondary Outcome
    Title Change From Baseline in Serum HBsAg Level at Week 4
    Description
    Time Frame Baseline; Week 4

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 15 14 14 5 18 17 17 5 16 17 13 6
    Mean (Standard Deviation) [log10 IU/mL]
    -0.009
    (0.0505)
    0.025
    (0.0514)
    -0.008
    (0.0516)
    -0.017
    (0.0600)
    -0.003
    (0.0574)
    0.014
    (0.0794)
    -0.001
    (0.0436)
    0.046
    (0.0648)
    -0.034
    (0.0375)
    -0.023
    (0.0529)
    -0.001
    (0.0627)
    -0.041
    (0.0955)
    7. Secondary Outcome
    Title Change From Baseline in Serum HBsAg Level at Week 8
    Description
    Time Frame Baseline; Week 8

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 16 13 15 4 17 17 17 4 16 17 12 6
    Mean (Standard Deviation) [log10 IU/mL]
    -0.029
    (0.0666)
    0.002
    (0.0544)
    -0.035
    (0.0649)
    -0.013
    (0.0440)
    0.000
    (0.0442)
    0.006
    (0.0772)
    0.020
    (0.0596)
    0.006
    (0.0600)
    -0.021
    (0.0376)
    -0.033
    (0.0487)
    -0.013
    (0.0426)
    -0.019
    (0.0483)
    8. Secondary Outcome
    Title Change From Baseline in Serum HBsAg Level at Week 12
    Description
    Time Frame Baseline; Week 12

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 14 14 15 5 17 17 16 5 16 16 12 6
    Mean (Standard Deviation) [log10 IU/mL]
    -0.050
    (0.0755)
    0.017
    (0.0646)
    -0.004
    (0.0546)
    -0.023
    (0.0623)
    -0.031
    (0.0817)
    -0.005
    (0.0843)
    -0.021
    (0.0716)
    -0.020
    (0.0666)
    -0.023
    (0.0545)
    -0.034
    (0.0549)
    -0.010
    (0.0621)
    -0.024
    (0.0661)
    9. Secondary Outcome
    Title Change From Baseline in Serum HBsAg Level at Week 48
    Description
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    Measure Participants 16 13 14 4 17 16 15 5 16 17 12 6
    Mean (Standard Deviation) [log10 IU/mL]
    -0.048
    (0.1054)
    -0.055
    (0.1400)
    -0.071
    (0.0857)
    -0.067
    (0.0831)
    -0.035
    (0.0923)
    -0.024
    (0.0679)
    -0.114
    (0.2169)
    -0.324
    (0.6811)
    -0.083
    (0.0858)
    -0.071
    (0.1076)
    -0.054
    (0.0715)
    -0.063
    (0.1011)

    Adverse Events

    Time Frame Adverse Events: First dose date up to Week 12 plus 30 days; All-Cause Mortality: Baseline up to Week 48
    Adverse Event Reporting Description Safety Analysis Set included all participants who received at least 1 dose of study drug.
    Arm/Group Title Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Arm/Group Description Vesatolimod 1 mg tablet once a week for 4 weeks Vesatolimod 2 mg tablet once a week for 4 weeks Vesatolimod 4 mg tablet once a week for 4 weeks Placebo tablet once a week for 4 weeks Vesatolimod 1 mg tablet once a week for 8 weeks Vesatolimod 2 mg tablet once a week for 8 weeks Vesatolimod 4 mg tablet once a week for 8 weeks Placebo tablet once a week for 8 weeks Vesatolimod 1 mg tablet once a week for 12 weeks Vesatolimod 2 mg tablet once a week for 12 weeks Vesatolimod 4 mg tablet once a week for 12 weeks Placebo tablet once a week for 12 weeks
    All Cause Mortality
    Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Serious Adverse Events
    Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 1/15 (6.7%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 1/14 (7.1%) 0/6 (0%)
    Eye disorders
    Cataract 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    General disorders
    Chills 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Pyrexia 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Nervous system disorders
    Headache 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Tremor 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Vascular disorders
    Hot flush 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Hypotension 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Other (Not Including Serious) Adverse Events
    Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 4 mg 4 Weeks (Cohort A) Placebo 4 Weeks (Cohort A) Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 4 mg 8 Weeks (Cohort B) Placebo 8 Weeks (Cohort B) Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 4 mg 12 Weeks (Cohort C) Placebo 12 Weeks (Cohort C)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/16 (62.5%) 12/15 (80%) 13/16 (81.3%) 4/5 (80%) 12/18 (66.7%) 7/17 (41.2%) 10/17 (58.8%) 4/5 (80%) 12/16 (75%) 12/17 (70.6%) 9/14 (64.3%) 3/6 (50%)
    Ear and labyrinth disorders
    Ear swelling 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Vertigo positional 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Eye disorders
    Asthenopia 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Diplopia 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Dry eye 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Glaucoma 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Photophobia 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Photopsia 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Visual acuity reduced 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Vitreous floaters 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Abdominal pain 1/16 (6.3%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Abdominal pain lower 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Abdominal pain upper 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 3/17 (17.6%) 1/14 (7.1%) 0/6 (0%)
    Dental caries 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Diarrhoea 2/16 (12.5%) 1/15 (6.7%) 1/16 (6.3%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 1/6 (16.7%)
    Epigastric discomfort 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Haemorrhoids 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Mouth cyst 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Mouth ulceration 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Nausea 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 3/18 (16.7%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Paraesthesia oral 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 1/6 (16.7%)
    Rectal haemorrhage 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Toothache 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 1/14 (7.1%) 0/6 (0%)
    Vomiting 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    General disorders
    Asthenia 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 1/5 (20%) 2/16 (12.5%) 1/17 (5.9%) 5/14 (35.7%) 0/6 (0%)
    Chills 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 1/17 (5.9%) 1/17 (5.9%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Fatigue 4/16 (25%) 3/15 (20%) 3/16 (18.8%) 1/5 (20%) 2/18 (11.1%) 0/17 (0%) 2/17 (11.8%) 1/5 (20%) 4/16 (25%) 2/17 (11.8%) 1/14 (7.1%) 1/6 (16.7%)
    Feeling cold 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 1/6 (16.7%)
    Feeling hot 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Influenza like illness 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 2/17 (11.8%) 0/5 (0%) 4/16 (25%) 0/17 (0%) 3/14 (21.4%) 0/6 (0%)
    Malaise 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Mucosal dryness 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Non-cardiac chest pain 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Pain 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 1/6 (16.7%)
    Pyrexia 2/16 (12.5%) 0/15 (0%) 3/16 (18.8%) 0/5 (0%) 0/18 (0%) 1/17 (5.9%) 1/17 (5.9%) 1/5 (20%) 2/16 (12.5%) 1/17 (5.9%) 3/14 (21.4%) 1/6 (16.7%)
    Thirst 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Vessel puncture site bruise 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Infections and infestations
    Bronchitis 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Diverticulitis 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Gastroenteritis 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 1/17 (5.9%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Gingivitis 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Influenza 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Nasopharyngitis 1/16 (6.3%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 1/17 (5.9%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Oral herpes 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Oral pustule 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Pharyngitis 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Respiratory tract infection viral 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Rhinitis 0/16 (0%) 1/15 (6.7%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Root canal infection 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Upper respiratory tract infection 1/16 (6.3%) 0/15 (0%) 1/16 (6.3%) 1/5 (20%) 1/18 (5.6%) 1/17 (5.9%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Viral upper respiratory tract infection 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Injury, poisoning and procedural complications
    Arthropod bite 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Fall 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Investigations
    Amylase increased 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 1/6 (16.7%)
    Blood pressure abnormal 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Lipase increased 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 1/6 (16.7%)
    Weight decreased 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Iron deficiency 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Back pain 0/16 (0%) 1/15 (6.7%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Bone pain 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 1/17 (5.9%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Bursitis 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 0/14 (0%) 1/6 (16.7%)
    Flank pain 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Muscle fatigue 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 1/6 (16.7%)
    Muscle spasms 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Muscular weakness 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Musculoskeletal chest pain 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Musculoskeletal pain 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Myalgia 0/16 (0%) 1/15 (6.7%) 1/16 (6.3%) 0/5 (0%) 1/18 (5.6%) 1/17 (5.9%) 1/17 (5.9%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 2/14 (14.3%) 0/6 (0%)
    Neck pain 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Osteoarthritis 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Pain in extremity 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Spinal pain 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Temporomandibular joint syndrome 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma of liver 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Nervous system disorders
    Disturbance in attention 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Dizziness 1/16 (6.3%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 2/18 (11.1%) 2/17 (11.8%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Dizziness postural 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Dysgeusia 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Headache 2/16 (12.5%) 3/15 (20%) 2/16 (12.5%) 2/5 (40%) 6/18 (33.3%) 2/17 (11.8%) 4/17 (23.5%) 2/5 (40%) 4/16 (25%) 3/17 (17.6%) 3/14 (21.4%) 3/6 (50%)
    Hypoaesthesia 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Mental impairment 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Parosmia 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Somnolence 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 2/16 (12.5%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Psychiatric disorders
    Agitation 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Anxiety 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Initial insomnia 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Insomnia 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 2/18 (11.1%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 1/6 (16.7%)
    Irritability 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Middle insomnia 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Panic attack 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Renal and urinary disorders
    Chromaturia 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Micturition frequency decreased 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Nocturia 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Pollakiuria 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Reproductive system and breast disorders
    Erectile dysfunction 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Nasal congestion 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Nasal obstruction 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Oropharyngeal pain 2/16 (12.5%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 2/18 (11.1%) 0/17 (0%) 0/17 (0%) 1/5 (20%) 0/16 (0%) 1/17 (5.9%) 0/14 (0%) 0/6 (0%)
    Pharyngeal oedema 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 1/16 (6.3%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Rhinitis allergic 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Rhinorrhoea 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 2/17 (11.8%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Sneezing 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Throat irritation 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 1/17 (5.9%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Skin and subcutaneous tissue disorders
    Acne 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 2/18 (11.1%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Alopecia 0/16 (0%) 0/15 (0%) 0/16 (0%) 1/5 (20%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Dermatitis 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 1/17 (5.9%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Nail growth abnormal 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Pruritus 2/16 (12.5%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Pruritus generalised 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Psoriasis 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 1/17 (5.9%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Rash erythematous 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Rash maculo-papular 0/16 (0%) 0/15 (0%) 1/16 (6.3%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Rash papular 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Urticaria 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)
    Vascular disorders
    Haematoma 0/16 (0%) 0/15 (0%) 0/16 (0%) 0/5 (0%) 0/18 (0%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 1/14 (7.1%) 0/6 (0%)
    Hypertension 0/16 (0%) 1/15 (6.7%) 0/16 (0%) 0/5 (0%) 1/18 (5.6%) 0/17 (0%) 0/17 (0%) 0/5 (0%) 0/16 (0%) 0/17 (0%) 0/14 (0%) 0/6 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02166047
    Other Study ID Numbers:
    • GS-US-283-1059
    • 2014-001400-22
    • ACTRN12614000628640
    First Posted:
    Jun 18, 2014
    Last Update Posted:
    Oct 14, 2020
    Last Verified:
    Sep 1, 2020