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Study to Evaluate the Safety and Efficacy of Vesatolimod in Antiretroviral Treated Human Immunodeficiency Virus (HIV-1) Infected Controllers

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT03060447
Collaborator
(none)
25
Enrollment
6
Locations
2
Arms
33.2
Actual Duration (Months)
4.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of a 10-dose regimen of vesatolimod in HIV-1 infected controllers on antiretroviral treatment (ART) and during analytical treatment interruption (ATI) following vesatolimod dosing.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
25 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 1b, Randomized, Double-Blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of GS-9620 in Antiretroviral Treated HIV-1 Infected Controllers
Actual Study Start Date :
May 9, 2017
Actual Primary Completion Date :
Feb 13, 2020
Actual Study Completion Date :
Feb 13, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Vesatolimod

Participants in Period 1 will receive 10 doses of vesatolimod (4 mg to 8 mg) once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) will discontinue ART and vesatolimod and will be monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restart ART during Period 2 due to virologic rebound will complete the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who complete 24 Weeks of ATI without restarting ART will move onto Period 3 and have 2 options. They can remain off ART for up to an additional 24 weeks. Those who restart ART at the start of Period 3 will complete ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.

Drug: Vesatolimod
Tablets Administered orally
Other Names:
  • GS-9620

    • Drug: ART
    ART regimens administered in accordance with their prescribing information. The following agents are allowed as part of the ART regimen: nucleoside reverse transcriptase inhibitors, raltegravir, dolutegravir (DTG), rilpivirine, and maraviroc.
    Experimental: Placebo

    Participants in Period 1 will receive 10 doses of placebo matched to vesatolimod once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) will discontinue ART and placebo and will be monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restart ART during Period 2 due to virologic rebound will complete the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who complete 24 Weeks of ATI without restarting ART will move onto Period 3 and have 2 options. They can remain off ART for up to an additional 24 weeks. Those who restart ART at the start of Period 3 will complete ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.

    Drug: Placebo
    Tablets Administered orally

    Drug: ART
    ART regimens administered in accordance with their prescribing information. The following agents are allowed as part of the ART regimen: nucleoside reverse transcriptase inhibitors, raltegravir, dolutegravir (DTG), rilpivirine, and maraviroc.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) [From first dose up to 30 days after permanent discontinuation of study drug (assessed maximum up to 33 months and 5 days)]

      AE was any untoward medical occurrence in a clinical study participant administered a medicinal product (MP), which did not necessarily had a causal relationship with treatment. AE was therefore any unfavorable and/or unintended sign, symptom, or disease temporally associated with use of MP, whether or not considered related to MP. TEAEs: AE with an onset date on or after the study drug start date and no later than 30 days after study drug stop date; or any AE leading to study drug discontinuation. TESAEs: event that resulted in following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; medically important event or reaction: such events might not have been immediately life-threatening or resulted in death or hospitalization but may jeopardize participant or may require intervention to prevent one of the other outcomes constituting SAEs.

    Secondary Outcome Measures

    1. Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 [Baseline and Dose 1: Days 2,8; Dose 2: Days 1,8; Dose 3: Days 1,8; Dose 4: Days 1,2,4,8; Dose 5: Day 1,8; Dose 6: Days 1,4,8; Dose 7: Days 1,8; Dose 8: Days 1,8; Dose 9: Days 1,8; Dose 10: Days 1,2,4,8,14]

      Plasma log 10 HIV-1 RNA was measured using Taqman version 2.0 assay with limit of quantification of 20 copies/mL.

    2. Time to Virologic Rebound [From Day 1 (Period 1) up to 24 weeks of Period 2 plus 6 months following virologic re-suppression on ART, an average of 17 months]

      Time to virologic rebound was analyzed using the Kaplan-Meier method at two cut-off values; ≥ 50 copies/mL and ≥ 200 copies/mL. Virologic rebound at ≥ 50 copies/mL was defined as 2 consecutive HIV-1 RNA measurements ≥ 50 copies/mL. Virologic rebound at ≥ 200 copies/mL was defined as 2 consecutive HIV-1 RNA measurements ≥ 200 copies/mL. The date of rebound was the first time HIV-1 RNA measurement ≥ 50 copies/mL or ≥ 200 respectively.

    3. Peak HIV-1 Viral Load During Period 2 [From Week 1 up to Week 24]

      For participants who did not restart ART, the maximum value of HIV-1 RNA measurements during ATI was used as the peak value and for participants who restarted ART, the maximum value of HIV-1 RNA measurements during ATI before the restart of ART was used as the peak value.

    4. Change in Plasma Viral Load Set-Point Following ATI [Pre-ART (Initial Screening Visit) and 24 weeks plus 6 months following virologic re-suppression on ART (maximum 33 months and 5 days)]

      Plasma viral load set-point values were calculated at pre-ART stage and following ATI. Change in plasma viral load set-point following ATI = viral set-point following ATI minus pre-ART set point. The plasma viral set-point following ATI was calculated as the geometric mean of all the HIV-1 RNA measurements between a start date and an end date. The start date and end date was provided by clinical based on blinded individual participant's data review.

    5. Change From Baseline in Levels of Serum Cytokines [Baseline and Dose 1: Day 2,8; Dose 4: Days 1,2,8; Dose 10: Days 1,2,8; ATI Remission Visit (12 weeks post ATI Visit: evaluated at maximum of 24 weeks); Early study drug discontinuation (7 days post- last ATI visit at Week 24)]

      Following Serum Cytokines Levels were evaluated: interferon-a (IFN-a), interleukin-1 receptor antagonist (IL-1RA), inducible protein-10 (IP-10) and inducible T cell alpha chemoattractant (ITAC).

    6. Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood [Baseline and Dose 1: Day 2; Dose 4: Days 1,2; Dose 10: Day 1,2; Early Study Drug Discontinuation (7 days post- last ATI visit at Week 24)]

      Following ISGs Levels were evaluated: Interferon-stimulated Gene 15 (ISG15), Oligoadenylate synthase-1 (OAS-1), and interferon-induced guanosine triphosphate-binding protein MX1. Fold change was calculated as postbaseline value divided by baseline value.

    7. Change From Baseline in Immune Cell Activation [Baseline and Dose 4: Days 1,2,4; Dose 6: Days 1,4; Dose 10: Days 1,2,4,14; ATI Remission Visit (12 weeks post ATI Visit: evaluated at maximum of 24 weeks)]

      Activation of Immune cells (T cells: CD4/CD38/HLADR, CD8/CD38/HLADR and NK cells: CD69+CD56+CD16+, CD69+CD56dimCD16neg, CD69+CD56brCD16dim) was measured by cytometry.

    8. Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod [Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.]

      Cmax is defined as the maximum concentration of drug.

    9. PK Parameter: AUClast of Vesatolimod [Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.]

      AUClast is defined as the concentration of drug from time zero to the last observable concentration.

    10. PK Parameter: AUCinf of Vesatolimod [Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.]

      AUCinf was defined as the concentration of drug extrapolated to infinite time.

    11. PK Parameter: %AUCexp of Vesatolimod [Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.]

      %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.

    12. PK Parameter: Tmax of Vesatolimod [Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.]

      Tmax is defined as the time (observed time point) of Cmax.

    Eligibility Criteria

    Criteria

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

    • Plasma HIV-1 ribonucleic acid (RNA) levels < 50 copies/mL at screening

    • Chronic HIV-1 infection (for ≥ 6 months) prior to ART initiation

    • Pre-ART Plasma HIV-1 RNA set point between 50 and ≤ 5,000 copies/mL measured within two years prior to ART initiation

    • On ART for ≥ 6 consecutive months prior to screening

    • Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable.

    • No documented history of resistance to any components of the current ART regimen

    • Availability of a fully active alternative ART regimen, in the opinion of the Investigator, in the event of discontinuation of the current ART regimen with development of resistance.

    • Hemoglobin ≥ 11.5 g/dL (males) or ≥ 11 g/dL (females)

    • White Blood Cells ≥ 2,500 cells/μL

    • Platelets ≥ 125,000/mL

    • Absolute Neutrophil Counts ≥ 1000 cells/μL

    • Cluster of Differentiation 4 (CD4)+ count ≥ 500 cells/μL

    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or bilirubin ≤ 2 × upper limit of normal (ULN)

    • Estimated glomerular filtration rate ≥ 60 mL/min

    • No autoimmune disease requiring on-going immunosuppression

    • No evidence of current hepatitis B virus (HBV) infection

    • No evidence of current hepatitis C virus (HCV) infection (positive anti-HCV antibody and negative HCV polymerase chain reaction (PCR) results are acceptable)

    • No documented history of pre-ART CD4 nadir < 200 cells/μL (unknown pre-ART CD4 nadir is acceptable)

    • No history of opportunistic illness indicative of stage 3 HIV

    • No acute febrile illness within 35 days prior to Pre-Baseline/ Day -13

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mills Clinical Research Los Angeles California United States 90069
    2 Zuckerberg San Francisco General San Francisco California United States 94110
    3 Midway Immunology & Research Center Fort Pierce Florida United States 34982
    4 Orlando Immunology Center Orlando Florida United States 32803
    5 Central Texas Clinical Research Austin Texas United States 78705
    6 Peter Shalit, MD Seattle Washington United States 98104

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT03060447
    Other Study ID Numbers:
    • GS-US-382-3961
    First Posted:
    Feb 23, 2017
    Last Update Posted:
    Apr 21, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Vesatolimod

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in the United States. The first participant was screened on 09 May 2017. The last study visit occurred on 13 February 2020.
    Pre-assignment Detail 31 participants were screened.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed antiretroviral treatment (ART). Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Period Title: Overall Study
    STARTED 17 8
    COMPLETED 15 8
    NOT COMPLETED 2 0

    Baseline Characteristics

    Arm/Group Title Vesatolimod Placebo Total
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Total of all reporting groups
    Overall Participants 17 8 25
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    49
    (11.4)
    42
    (9.4)
    46
    (11.2)
    Sex: Female, Male (Count of Participants)
    Female
    4
    23.5%
    0
    0%
    4
    16%
    Male
    13
    76.5%
    8
    100%
    21
    84%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    12.5%
    1
    4%
    Not Hispanic or Latino
    17
    100%
    7
    87.5%
    24
    96%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    6
    35.3%
    2
    25%
    8
    32%
    White
    11
    64.7%
    6
    75%
    17
    68%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    HIV-1 RNA (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    1.30
    (0.108)
    1.28
    (0.000)
    1.30
    (0.089)
    HIV-1 RNA Category (Count of Participants)
    < 50 copies/mL
    16
    94.1%
    8
    100%
    24
    96%
    ≥ 50 copies/mL
    1
    5.9%
    0
    0%
    1
    4%
    Pre-ART Plasma Viral Set-point (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    3.15
    (0.275)
    3.08
    (0.469)
    3.13
    (0.340)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs)
    Description AE was any untoward medical occurrence in a clinical study participant administered a medicinal product (MP), which did not necessarily had a causal relationship with treatment. AE was therefore any unfavorable and/or unintended sign, symptom, or disease temporally associated with use of MP, whether or not considered related to MP. TEAEs: AE with an onset date on or after the study drug start date and no later than 30 days after study drug stop date; or any AE leading to study drug discontinuation. TESAEs: event that resulted in following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; medically important event or reaction: such events might not have been immediately life-threatening or resulted in death or hospitalization but may jeopardize participant or may require intervention to prevent one of the other outcomes constituting SAEs.
    Time Frame From first dose up to 30 days after permanent discontinuation of study drug (assessed maximum up to 33 months and 5 days)

    Outcome Measure Data

    Analysis Population Description
    The Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug. Per planned analysis, this outcome measure was analyzed by vesatolimod dose level and placebo.
    Arm/Group Title Vesatolimod 4 mg Vesatolimod 4/6 mg Vesatolimod 6 mg Vesatolimod 6/8 mg Vesatolimod 8 mg Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod 4 mg tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of vesatolimod 4 mg or 6 mg tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of vesatolimod 6 mg tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of vesatolimod 6 mg or 8 mg tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of vesatolimod 8 mg tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 2 4 5 3 3 8
    TESAEs
    0
    0%
    0
    0%
    0
    0%
    33.3
    NaN
    0
    NaN
    0
    NaN
    TEAEs
    100.00
    588.2%
    75.00
    937.5%
    100.00
    400%
    100.00
    NaN
    100.00
    NaN
    75.00
    NaN
    2. Secondary Outcome
    Title Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0
    Description Plasma log 10 HIV-1 RNA was measured using Taqman version 2.0 assay with limit of quantification of 20 copies/mL.
    Time Frame Baseline and Dose 1: Days 2,8; Dose 2: Days 1,8; Dose 3: Days 1,8; Dose 4: Days 1,2,4,8; Dose 5: Day 1,8; Dose 6: Days 1,4,8; Dose 7: Days 1,8; Dose 8: Days 1,8; Dose 9: Days 1,8; Dose 10: Days 1,2,4,8,14

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set (included all participants who were randomized into the study and received at least one dose of study drug) with available data were analyzed.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 17 8
    Change at Dose 1: Day 2
    -0.01
    (0.027)
    0.00
    (0.000)
    Change at Dose 1: Day 8
    0.05
    (0.212)
    0.00
    (0.000)
    Change at Dose 2: Day 1
    0.09
    (0.372)
    0.00
    (0.000)
    Change at Dose 2: Day 8
    -0.03
    (0.111)
    0.00
    (0.000)
    Change at Dose 3: Day 1
    -0.03
    (0.111)
    0.00
    (0.000)
    Change at Dose 3: Day 8
    -0.03
    (0.111)
    0.00
    (0.000)
    Change at Dose 4: Day 1
    -0.03
    (0.111)
    0.00
    (0.000)
    Change at Dose 4: Day 2
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 4: Day 4
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 4: Day 8
    -0.03
    (0.111)
    0.00
    (0.000)
    Change at Dose 5: Day 1
    -0.03
    (0.111)
    0.00
    (0.000)
    Change at Dose 5: Day 8
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 6: Day 1
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 6: Day 4
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 6: Day 8
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 7: Day 1
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 7: Day 8
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 8: Day 1
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 8: Day 8
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 9: Day 1
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 9: Day 8
    0.00
    (0.000)
    0.00
    (0.000)
    Change at Dose 10: Day 1
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 10: Day 2
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 10: Day 4
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 10: Day 8
    -0.03
    (0.115)
    0.00
    (0.000)
    Change at Dose 10: Day 14
    -0.03
    (0.115)
    0.00
    (0.000)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 1: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.55
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 1: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.54
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 2: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.54
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 2: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.54
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 3: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.54
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 3: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.57
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.54
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 4: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 4: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.61
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 5: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.54
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 5: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 6: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 6: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 6: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 7: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 7 - Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 8: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 8: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 9: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 9: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 10: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 10: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments Dose 10: Day 14
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    3. Secondary Outcome
    Title Time to Virologic Rebound
    Description Time to virologic rebound was analyzed using the Kaplan-Meier method at two cut-off values; ≥ 50 copies/mL and ≥ 200 copies/mL. Virologic rebound at ≥ 50 copies/mL was defined as 2 consecutive HIV-1 RNA measurements ≥ 50 copies/mL. Virologic rebound at ≥ 200 copies/mL was defined as 2 consecutive HIV-1 RNA measurements ≥ 200 copies/mL. The date of rebound was the first time HIV-1 RNA measurement ≥ 50 copies/mL or ≥ 200 respectively.
    Time Frame From Day 1 (Period 1) up to 24 weeks of Period 2 plus 6 months following virologic re-suppression on ART, an average of 17 months

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 15 8
    ≥ 50 Copies/mL
    4.3
    4.0
    ≥ 200 Copies/mL
    5.1
    4.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ≥ 50 Copies/mL
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.035
    Comments
    Method Log Rank
    Comments P-value between treatment groups was based on log-rank test.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ≥ 200 Copies/mL
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.024
    Comments
    Method Log Rank
    Comments P-value between treatment groups was based on log-rank test.
    4. Secondary Outcome
    Title Peak HIV-1 Viral Load During Period 2
    Description For participants who did not restart ART, the maximum value of HIV-1 RNA measurements during ATI was used as the peak value and for participants who restarted ART, the maximum value of HIV-1 RNA measurements during ATI before the restart of ART was used as the peak value.
    Time Frame From Week 1 up to Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 15 8
    Median (Inter-Quartile Range) [Log10 copies/mL]
    4.21
    3.97
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.67
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values between treatment groups were based on Wilcoxon rank sum test.
    5. Secondary Outcome
    Title Change in Plasma Viral Load Set-Point Following ATI
    Description Plasma viral load set-point values were calculated at pre-ART stage and following ATI. Change in plasma viral load set-point following ATI = viral set-point following ATI minus pre-ART set point. The plasma viral set-point following ATI was calculated as the geometric mean of all the HIV-1 RNA measurements between a start date and an end date. The start date and end date was provided by clinical based on blinded individual participant's data review.
    Time Frame Pre-ART (Initial Screening Visit) and 24 weeks plus 6 months following virologic re-suppression on ART (maximum 33 months and 5 days)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 15 7
    Median (Inter-Quartile Range) [Log10 copies/mL]
    -0.37
    -0.28
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.78
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values between treatment groups were based on Wilcoxon rank sum test.
    6. Secondary Outcome
    Title Change From Baseline in Levels of Serum Cytokines
    Description Following Serum Cytokines Levels were evaluated: interferon-a (IFN-a), interleukin-1 receptor antagonist (IL-1RA), inducible protein-10 (IP-10) and inducible T cell alpha chemoattractant (ITAC).
    Time Frame Baseline and Dose 1: Day 2,8; Dose 4: Days 1,2,8; Dose 10: Days 1,2,8; ATI Remission Visit (12 weeks post ATI Visit: evaluated at maximum of 24 weeks); Early study drug discontinuation (7 days post- last ATI visit at Week 24)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 17 8
    IFN-a, Baseline
    0.02
    (0.036)
    0.05
    (0.075)
    IFN-a,Change at Dose 1: Day 2
    0.41
    (0.834)
    -0.01
    (0.073)
    IFN-a,Change at Dose 1: Day 8
    0.14
    (0.447)
    0.04
    (0.129)
    IFN-a,Change at Dose 4: Day 1
    -0.01
    (0.030)
    0.10
    (0.358)
    IFN-a,Change at Dose 4: Day 2
    0.75
    (2.361)
    -0.01
    (0.065)
    IFN-a,Change at Dose 4: Day 8
    0.01
    (0.064)
    -0.03
    (0.077)
    IFN-a,Change at Dose 10: Day 1
    -0.01
    (0.031)
    -0.03
    (0.056)
    IFN-a,Change at Dose 10: Day 2
    0.51
    (1.028)
    -0.02
    (0.055)
    IFN-a,Change at Dose 10: Day 8
    0.01
    (0.072)
    -0.04
    (0.065)
    IFN-a,Change at ATI Remission Visit
    -0.03
    (0.059)
    0.17
    (0.301)
    IFN-a,Change at Early study drug discontinuation
    0.00
    IL-1RA, Baseline
    2346.1
    (3743.44)
    882.9
    (306.75)
    IL-1RA,Change at Dose 1: Day 2
    2797.6
    (2908.21)
    94.8
    (190.53)
    IL-1RA,Change at Dose 1: Day 8
    -326.9
    (914.43)
    1004.9
    (2432.36)
    IL-1RA,Change at Dose 4: Day 1
    390.4
    (856.29)
    42.2
    (227.90)
    IL-1RA,Change at Dose 4: Day 2
    5140.4
    (8692.35)
    186.4
    (449.94)
    IL-1RA,Change at Dose 4: Day 8
    -63.9
    (1749.75)
    -143.5
    (226.83)
    IL-1RA,Change at Dose 10: Day 1
    -160.9
    (1229.91)
    563.9
    (1201.78)
    IL-1RA,Change at Dose 10: Day 2
    3790.2
    (6401.27)
    14.1
    (467.90)
    IL-1RA,Change at Dose 10: Day 8
    -77.6
    (521.52)
    -13.9
    (308.80)
    IL-1RA,Change at ATI Remission Visit
    -161.7
    (1030.42)
    491.1
    (306.12)
    IL-1RA,Change at Early study drug discontinuation
    222.4
    IP-10, Baseline
    161.0
    (82.04)
    178.5
    (103.50)
    IP-10, Change at Dose 1: Day 2
    554.1
    (693.55)
    -23.9
    (52.24)
    IP-10,Change at Dose 1: Day 8
    38.8
    (126.82)
    34.5
    (182.93)
    IP-10,Change at Dose 4: Day 1
    27.8
    (71.62)
    -25.3
    (46.15)
    IP-10,Change at Dose 4: Day 2
    337.9
    (487.83)
    -13.8
    (78.10)
    IP-10,Change at Dose 4: Day 8
    23.4
    (58.50)
    -59.0
    (58.04)
    IP-10,Change at Dose 10: Day 1
    19.1
    (44.13)
    -22.8
    (54.29)
    IP-10,Change at Dose 10: Day 2
    554.6
    (893.70)
    -17.5
    (50.94)
    IP-10, Change at Dose 10: Day 8
    18.1
    (82.14)
    -51.1
    (57.23)
    IP-10,Change at ATI Remission
    47.5
    (48.42)
    26.2
    (92.41)
    IP-10,Change at Early Study Drug Discontinuation
    0.7
    ITAC, Baseline
    71.8
    (108.10)
    206.3
    (329.55)
    ITAC, Change at Dose 1: Day 2
    50.4
    (80.46)
    -13.9
    (42.68)
    ITAC,Change at Dose 1: Day 8
    11.5
    (34.78)
    -10.4
    (44.02)
    ITAC, Change at Dose 4: Day 1
    8.0
    (25.97)
    -25.4
    (65.76)
    ITAC,Change at Dose 4: Day 2
    48.0
    (78.14)
    -8.9
    (33.81)
    ITAC, Change at Dose 4: Day 8
    2.0
    (24.20)
    5.0
    (27.98)
    ITAC,Change at Dose 10: Day 1
    -1.6
    (19.11)
    -8.4
    (33.91)
    ITAC,Change at Dose 10: Day 2
    69.1
    (181.55)
    -1.0
    (27.68)
    ITAC,Change at Dose 10: Day 8
    2.2
    (12.19)
    -7.4
    (22.50)
    ITAC,Change at ATI Remission
    19.1
    (20.44)
    39.6
    (88.54)
    ITAC,Change at Early Study Drug Discontinuation
    31.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.34
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Dose 1: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.11
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Dose 1: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.81
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.83
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.12
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Dose 4: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.45
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.25
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, Dose 10: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.16
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IFN-a, ATI Remission Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.27
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.35
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, Dose 1: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, Dose 1: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.15
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.30
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg
    Comments IL-1RA, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, Dose 4: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.49
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.25
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.055
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, Dose 10: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.90
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IL-1RA, ATI Remission Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.39
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.75
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Dose 1: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Dose 1: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.69
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.15
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Dose 4: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.030
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.087
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 29
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, Dose 10: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.066
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 30
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments IP-10, ATI Remission
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.86
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 31
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.19
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 32
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Dose 1: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.021
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 33
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Dose 1: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.31
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 34
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.10
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 35
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 36
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Dose 4: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.69
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 37
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.46
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 38
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.21
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 39
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, Dose 10: Day 8
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.67
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 40
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ITAC, ATI Remission
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.60
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    7. Secondary Outcome
    Title Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood
    Description Following ISGs Levels were evaluated: Interferon-stimulated Gene 15 (ISG15), Oligoadenylate synthase-1 (OAS-1), and interferon-induced guanosine triphosphate-binding protein MX1. Fold change was calculated as postbaseline value divided by baseline value.
    Time Frame Baseline and Dose 1: Day 2; Dose 4: Days 1,2; Dose 10: Day 1,2; Early Study Drug Discontinuation (7 days post- last ATI visit at Week 24)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 17 8
    ISG15, Dose 1: Day 2
    19.53
    (15.548)
    1.06
    (0.320)
    ISG15, Dose 4: Day 1
    3.35
    (5.212)
    1.24
    (0.343)
    ISG15, Dose 4: Day 2
    19.09
    (15.113)
    8.41
    (20.782)
    ISG15, Dose 10: Day 1
    1.62
    (0.742)
    1.02
    (0.223)
    ISG15, Dose 10: Day 2
    19.71
    (20.209)
    1.02
    (0.366)
    ISG15, Early Study Drug Discontinuation
    1.14
    OAS-1, Dose 1: Day 2
    6.83
    (4.225)
    1.07
    (0.285)
    OAS-1, Dose 4: Day 1
    2.21
    (2.087)
    1.13
    (0.395)
    OAS-1, Dose 4: Day 2
    7.44
    (4.650)
    2.62
    (4.676)
    OAS-1, Dose 10: Day 1
    1.47
    (0.665)
    1.03
    (0.218)
    OAS-1, Dose 10: Day 2
    6.83
    (5.189)
    1.04
    (0.162)
    OAS-1, Early Study Drug Discontinuation
    1.08
    MX1, Dose 1: Day 2
    9.36
    (6.873)
    1.06
    (0.249)
    MX1, Dose 4: Day 1
    2.98
    (4.650)
    1.17
    (0.312)
    MX1, Dose 4: Day 2
    9.91
    (8.061)
    3.49
    (6.957)
    MX1, Dose 10: Day 1
    1.59
    (0.844)
    1.03
    (0.226)
    MX1, Dose 10: Day 2
    10.29
    (8.862)
    0.98
    (0.232)
    MX1, Early Study Drug Discontinuation
    1.06
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ISG15, Dose 1: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ISG15, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.58
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ISG15, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments
    Type of Statistical Test Superiority
    Comments ISG15, Dose 10: Day 1
    Statistical Test of Hypothesis p-Value 0.031
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments ISG15, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments OAS-1, Dose 1: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments OAS-1, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.057
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments OAS-1, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments OAS-1, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.057
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments OAS-1, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments MX1, Dose 1: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments MX1, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.17
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments MX1, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments
    Type of Statistical Test Superiority
    Comments MX1, Dose 10: Day 1
    Statistical Test of Hypothesis p-Value 0.100
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments MX1, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    8. Secondary Outcome
    Title Change From Baseline in Immune Cell Activation
    Description Activation of Immune cells (T cells: CD4/CD38/HLADR, CD8/CD38/HLADR and NK cells: CD69+CD56+CD16+, CD69+CD56dimCD16neg, CD69+CD56brCD16dim) was measured by cytometry.
    Time Frame Baseline and Dose 4: Days 1,2,4; Dose 6: Days 1,4; Dose 10: Days 1,2,4,14; ATI Remission Visit (12 weeks post ATI Visit: evaluated at maximum of 24 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 9 6
    CD4/CD38/HLADR, Baseline
    2.7
    (0.94)
    2.3
    (1.04)
    CD4/CD38/HLADR,Change at Dose 4: Day 1
    0.4
    (0.58)
    -0.3
    (0.38)
    CD4/CD38/HLADR,Change at Dose 4: Day 2
    0.9
    (0.88)
    0.4
    (1.02)
    CD4/CD38/HLADR,Change at Dose 4: Day 4
    0.7
    (0.53)
    -0.3
    (0.74)
    CD4/CD38/HLADR,Change at Dose 6: Day 1
    0.5
    (0.41)
    -0.2
    (0.90)
    CD4/CD38/HLADR,Change at Dose 6: Day 4
    0.9
    (0.41)
    -0.1
    (1.20)
    CD4/CD38/HLADR,Change at Dose 10: Day 1
    1.0
    (0.56)
    -0.4
    (0.45)
    CD4/CD38/HLADR,Change at Dose 10: Day 2
    2.6
    (0.11)
    -0.3
    (0.75)
    CD4/CD38/HLADR,Change at Dose 10: Day 4
    1.0
    (1.60)
    -0.2
    (1.45)
    CD4/CD38/HLADR,Change at Dose 10: Day 14
    0.5
    (0.36)
    0.1
    (1.16)
    CD4/CD38/HLADR,Change at ATI Remission
    1.3
    (1.63)
    CD8/CD38/HLADR, Baseline
    5.4
    (2.43)
    5.2
    (2.86)
    CD8/CD38/HLADR,Change at Dose 4: Day 1
    0.6
    (1.41)
    -0.8
    (1.23)
    CD8/CD38/HLADR,Change at Dose 4: Day 2
    1.6
    (1.19)
    0.2
    (2.06)
    CD8/CD38/HLADR,Change at Dose 4: Day 4
    0.8
    (0.56)
    -0.9
    (1.83)
    CD8/CD38/HLADR,Change at Dose 6: Day 1
    -0.6
    (0.70)
    -1.1
    (1.56)
    CD8/CD38/HLADR,Change at Dose 6: Day 4
    1.5
    (1.53)
    -0.7
    (2.14)
    CD8/CD38/HLADR,Change at Dose 10: Day 1
    1.5
    (2.82)
    -1.3
    (1.77)
    CD8/CD38/HLADR,Change at Dose 10: Day 2
    7.0
    (4.83)
    -1.2
    (2.09)
    CD8/CD38/HLADR,Change at Dose 10: Day 4
    3.0
    (3.25)
    -1.3
    (2.31)
    CD8/CD38/HLADR,Change at Dose 10: Day 14
    1.6
    (3.03)
    0.0
    (2.81)
    CD8/CD38/HLADR,Change at ATI Remission Visit
    6.0
    (6.41)
    CD69+CD56+CD16+, Baseline
    7.5
    (7.04)
    6.7
    (6.31)
    CD69+CD56+CD16+,Change at Dose 4: Day 1
    -2.2
    (5.43)
    -0.4
    (3.24)
    CD69+CD56+CD16+,Change at Dose 4: Day 2
    4.5
    (7.45)
    0.5
    (2.81)
    CD69+CD56+CD16+,Change at Dose 4: Day 4
    1.0
    (3.04)
    0.0
    (5.12)
    CD69+CD56+CD16+,Change at Dose 6: Day 1
    0.2
    (2.36)
    0.4
    (4.32)
    CD69+CD56+CD16+,Change at Dose 6: Day 4
    0.9
    (0.95)
    -1.5
    (4.78)
    CD69+CD56+CD16+,Change at Dose 10: Day 1
    0.5
    (0.61)
    -1.2
    (4.67)
    CD69+CD56+CD16+,Change at Dose 10: Day 2
    11.1
    (2.72)
    -2.2
    (5.81)
    CD69+CD56+CD16+,Change at Dose 10: Day 4
    1.7
    (1.99)
    -1.4
    (5.10)
    CD69+CD56+CD16+,Change at Dose 10: Day 14
    0.8
    (6.77)
    -0.4
    (3.92)
    CD69+CD56+CD16+,Change at ATI Remission Visit
    -1.7
    (1.34)
    CD69+CD56dimCD16neg, Baseline
    12.2
    (6.41)
    11.3
    (10.37)
    CD69+CD56dimCD16neg,Change at Dose 4: Day 1
    -1.8
    (5.13)
    -0.7
    (2.72)
    CD69+CD56dimCD16neg,Change at Dose 4: Day 2
    6.7
    (4.95)
    -0.8
    (4.10)
    CD69+CD56dimCD16neg,Change at Dose 4: Day 4
    1.9
    (6.02)
    -1.1
    (6.50)
    CD69+CD56dimCD16neg,Change at Dose 6: Day 1
    -0.7
    (5.36)
    -3.0
    (7.89)
    CD69+CD56dimCD16neg,Change at Dose 6: Day 4
    2.6
    (3.81)
    -3.0
    (7.00)
    CD69+CD56dimCD16neg,Change at Dose 10: Day 1
    -0.7
    (5.15)
    -3.7
    (7.02)
    CD69+CD56dimCD16neg,Change at Dose 10: Day 2
    23.9
    (8.15)
    -4.2
    (7.94)
    CD69+CD56dimCD16neg,Change at Dose 10: Day 4
    2.0
    (2.55)
    -2.0
    (6.70)
    CD69+CD56dimCD16neg,Change at Dose 10: Day 14
    1.6
    (4.89)
    -2.5
    (8.49)
    CD69+CD56dimCD16neg,Change at Dose 10: ATI Remission
    -7.3
    (13.15)
    CD69+CD56brCD16dim, Baseline
    5.0
    (2.68)
    2.6
    (1.02)
    CD69+CD56brCD16dim,Change at Dose 4: Day 1
    -1.5
    (1.46)
    -0.3
    (1.89)
    CD69+CD56brCD16dim,Change at Dose 4: Day 2
    1.0
    (2.98)
    0.6
    (2.49)
    CD69+CD56brCD16dim,Change at Dose 4: Day 4
    0.9
    (1.63)
    2.9
    (2.13)
    CD69+CD56brCD16dim,Change at Dose 6: Day 1
    1.9
    (2.09)
    1.5
    (2.90)
    CD69+CD56brCD16dim,Change at Dose 6: Day 4
    6.2
    (6.68)
    0.2
    (1.72)
    CD69+CD56brCD16dim,Change at Dose 10: Day 1
    5.0
    (7.00)
    1.3
    (1.72)
    CD69+CD56brCD16dim,Change at Dose 10: Day 2
    17.2
    (16.49)
    2.2
    (5.08)
    CD69+CD56brCD16dim,Change at Dose 10: Day 4
    0.0
    (1.46)
    3.3
    (3.70)
    CD69+CD56brCD16dim,Change at Dose 10: Day 14
    2.7
    (3.14)
    0.9
    (2.93)
    CD69+CD56brCD16dim,Change at ATI Remission
    0.2
    (0.91)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7469
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1207
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4113
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 4: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1113
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 6: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2410
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 6: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1098
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0369
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0814
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 10: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1658
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD4/CD38/HLADR, Dose 10: Day 14
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9431
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6514
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0821
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2353
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 4: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1779
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 6: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7491
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 6: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0700
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3711
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0814
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 10: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0700
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD8/CD38/HLADR, Dose 10: Day 14
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8303
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9530
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1735
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2971
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 4: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 6: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 6: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3374
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7656
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0814
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 29
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 10: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3374
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 30
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56+CD16+, Dose 10: Day 14
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4320
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 31
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8597
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 32
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 33
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0306
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 34
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 4: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8345
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 35
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 6: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9151
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 36
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 6: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1098
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 37
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 38
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0814
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 39
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 10: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4555
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 40
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56dimCD16neg, Dose 10: Day 14
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6171
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 41
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Baseline
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0677
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 42
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Dose 4: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4712
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 43
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Dose 4: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6889
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 44
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Dose 4: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1437
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 45
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Dose 6: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7491
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 46
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Dose 6: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0700
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 47
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Dose 10: Day 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7656
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 48
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Dose 10: Day 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1752
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 49
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments CD69+CD56brCD16dim, Dose 10: Day 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0700
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    Statistical Analysis 50
    Statistical Analysis Overview Comparison Group Selection Vesatolimod 4 mg, Vesatolimod 4/6 mg
    Comments
    Type of Statistical Test Superiority
    Comments CD69+CD56brCD16dim, Dose 10: Day 14
    Statistical Test of Hypothesis p-Value 0.2246
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments P-values are based on two-sided Wilcoxon rank sum tests.
    9. Secondary Outcome
    Title Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod
    Description Cmax is defined as the maximum concentration of drug.
    Time Frame Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.

    Outcome Measure Data

    Analysis Population Description
    The vesatolimod PK Analysis Set included all participants who were randomized into the study, received at least 1 dose of active vesatolimod, and had at least 1 non-missing post baseline concentration value for vesatolimod. Per planned analysis this outcome measure was analyzed by actual treatment received (i.e. 'Vesatolimod').
    Arm/Group Title Vesatolimod
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 17
    Mean (Standard Deviation) [pg/mL]
    7149.6
    (7662.17)
    10. Secondary Outcome
    Title PK Parameter: AUClast of Vesatolimod
    Description AUClast is defined as the concentration of drug from time zero to the last observable concentration.
    Time Frame Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.

    Outcome Measure Data

    Analysis Population Description
    Participants in the vesatolimod PK Analysis Set were analyzed. Per planned analysis this outcome measure was analyzed by actual treatment received (i.e. 'Vesatolimod').
    Arm/Group Title Vesatolimod
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 17
    Mean (Standard Deviation) [hour*pg/ml]
    49323.5
    (48542.34)
    11. Secondary Outcome
    Title PK Parameter: AUCinf of Vesatolimod
    Description AUCinf was defined as the concentration of drug extrapolated to infinite time.
    Time Frame Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.

    Outcome Measure Data

    Analysis Population Description
    Participants in the vesatolimod PK Analysis Set with available data were analyzed. Per planned analysis this outcome measure was analyzed by actual treatment received (i.e. 'Vesatolimod').
    Arm/Group Title Vesatolimod
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 16
    Mean (Standard Deviation) [hour*pg/mL]
    60040.3
    (59280.72)
    12. Secondary Outcome
    Title PK Parameter: %AUCexp of Vesatolimod
    Description %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
    Time Frame Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.

    Outcome Measure Data

    Analysis Population Description
    Participants in the vesatolimod PK Analysis Set with available data were analyzed. Per planned analysis this outcome measure was analyzed by actual treatment received (i.e. 'Vesatolimod').
    Arm/Group Title Vesatolimod
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 16
    Mean (Standard Deviation) [Percentage of AUC]
    22.4
    (7.90)
    13. Secondary Outcome
    Title PK Parameter: Tmax of Vesatolimod
    Description Tmax is defined as the time (observed time point) of Cmax.
    Time Frame Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit.

    Outcome Measure Data

    Analysis Population Description
    Participants in the vesatolimod PK Analysis Set with available data were analyzed. Per planned analysis this outcome measure was analyzed by actual treatment received (i.e. 'Vesatolimod').
    Arm/Group Title Vesatolimod
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Measure Participants 16
    Median (Full Range) [hour]
    2.00

    Adverse Events

    Time Frame From first dose up to 30 days after permanent discontinuation of study drug (assessed maximum up to 33 months and 5 days)
    Adverse Event Reporting Description The Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
    Arm/Group Title Vesatolimod Placebo
    Arm/Group Description Participants in Period 1 received 10 doses of vesatolimod (4 mg to 8 mg) tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and vesatolimod and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants in Period 1 received 10 doses of placebo matched to vesatolimod tablets once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) discontinued ART and placebo and were monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restarted ART during Period 2 due to virologic rebound completed the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who completed 24 Weeks of ATI without restarting ART moved onto Period 3 and had 2 options. They remained off ART for up to an additional 24 weeks. Those who restarted ART at the start of Period 3 completed ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    All Cause Mortality
    Vesatolimod Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/17 (0%) 0/8 (0%)
    Serious Adverse Events
    Vesatolimod Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/17 (5.9%) 0/8 (0%)
    Gastrointestinal disorders
    Chronic gastritis 1/17 (5.9%) 0/8 (0%)
    Other (Not Including Serious) Adverse Events
    Vesatolimod Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/17 (94.1%) 6/8 (75%)
    Blood and lymphatic system disorders
    Lymphadenopathy 3/17 (17.6%) 0/8 (0%)
    Cardiac disorders
    Bradycardia 1/17 (5.9%) 0/8 (0%)
    Eye disorders
    Blepharospasm 1/17 (5.9%) 0/8 (0%)
    Gastrointestinal disorders
    Abdominal pain lower 1/17 (5.9%) 0/8 (0%)
    Abdominal pain upper 1/17 (5.9%) 0/8 (0%)
    Angular cheilitis 1/17 (5.9%) 0/8 (0%)
    Chapped lips 1/17 (5.9%) 0/8 (0%)
    Diarrhoea 1/17 (5.9%) 0/8 (0%)
    Faeces soft 1/17 (5.9%) 0/8 (0%)
    Nausea 5/17 (29.4%) 1/8 (12.5%)
    Swollen tongue 1/17 (5.9%) 0/8 (0%)
    Umbilical hernia 1/17 (5.9%) 1/8 (12.5%)
    Vomiting 1/17 (5.9%) 0/8 (0%)
    General disorders
    Chills 4/17 (23.5%) 0/8 (0%)
    Fatigue 3/17 (17.6%) 0/8 (0%)
    Malaise 2/17 (11.8%) 0/8 (0%)
    Pyrexia 3/17 (17.6%) 0/8 (0%)
    Vessel puncture site bruise 2/17 (11.8%) 0/8 (0%)
    Infections and infestations
    Acute sinusitis 2/17 (11.8%) 0/8 (0%)
    Gastroenteritis viral 1/17 (5.9%) 1/8 (12.5%)
    Laryngitis 1/17 (5.9%) 0/8 (0%)
    Nasopharyngitis 2/17 (11.8%) 0/8 (0%)
    Sinusitis 3/17 (17.6%) 2/8 (25%)
    Tinea cruris 1/17 (5.9%) 0/8 (0%)
    Urinary tract infection 1/17 (5.9%) 0/8 (0%)
    Viral infection 1/17 (5.9%) 0/8 (0%)
    Injury, poisoning and procedural complications
    Foot fracture 0/17 (0%) 1/8 (12.5%)
    Procedural pain 1/17 (5.9%) 0/8 (0%)
    Rib fracture 1/17 (5.9%) 0/8 (0%)
    Tooth fracture 1/17 (5.9%) 0/8 (0%)
    Investigations
    Weight decreased 1/17 (5.9%) 0/8 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 1/17 (5.9%) 0/8 (0%)
    Gout 1/17 (5.9%) 0/8 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/17 (17.6%) 0/8 (0%)
    Back pain 1/17 (5.9%) 1/8 (12.5%)
    Bursitis 0/17 (0%) 1/8 (12.5%)
    Muscle spasms 1/17 (5.9%) 0/8 (0%)
    Myalgia 1/17 (5.9%) 0/8 (0%)
    Pain in extremity 0/17 (0%) 1/8 (12.5%)
    Pain in jaw 0/17 (0%) 1/8 (12.5%)
    Tendonitis 1/17 (5.9%) 0/8 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Seborrhoeic keratosis 1/17 (5.9%) 0/8 (0%)
    Nervous system disorders
    Dizziness 1/17 (5.9%) 0/8 (0%)
    Headache 5/17 (29.4%) 3/8 (37.5%)
    Neuropathy peripheral 1/17 (5.9%) 0/8 (0%)
    Sciatica 1/17 (5.9%) 0/8 (0%)
    Pregnancy, puerperium and perinatal conditions
    Morning sickness 1/17 (5.9%) 0/8 (0%)
    Reproductive system and breast disorders
    Haematospermia 0/17 (0%) 1/8 (12.5%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/17 (5.9%) 0/8 (0%)
    Dyspnoea exertional 1/17 (5.9%) 0/8 (0%)
    Epistaxis 1/17 (5.9%) 0/8 (0%)
    Nasal congestion 1/17 (5.9%) 0/8 (0%)
    Nasal disorder 0/17 (0%) 1/8 (12.5%)
    Oropharyngeal pain 1/17 (5.9%) 0/8 (0%)
    Rhinitis allergic 0/17 (0%) 1/8 (12.5%)
    Sinus congestion 1/17 (5.9%) 0/8 (0%)
    Skin and subcutaneous tissue disorders
    Eczema 1/17 (5.9%) 0/8 (0%)
    Hand dermatitis 2/17 (11.8%) 0/8 (0%)
    Vascular disorders
    Hypertension 1/17 (5.9%) 0/8 (0%)
    Phlebitis 1/17 (5.9%) 0/8 (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:
    NCT03060447
    Other Study ID Numbers:
    • GS-US-382-3961
    First Posted:
    Feb 23, 2017
    Last Update Posted:
    Apr 21, 2021
    Last Verified:
    Mar 1, 2021