HIV-1 Infection
Conditions
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.
Interventions
DRUGVesatolimod
Tablets Administered orally
DRUGPlacebo
Tablets Administered orally
DRUGART
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.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
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 details
31 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Vesatolimod 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. | 17 |
| Placebo 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. | 8 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Vesatolimod |
|---|---|---|---|
| Age, Continuous | 42 years STANDARD_DEVIATION 9.4 | 46 years STANDARD_DEVIATION 11.2 | 49 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 24 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HIV-1 RNA | 1.28 log10 copies/mL STANDARD_DEVIATION 0 | 1.30 log10 copies/mL STANDARD_DEVIATION 0.089 | 1.30 log10 copies/mL STANDARD_DEVIATION 0.108 |
| HIV-1 RNA Category < 50 copies/mL | 8 Participants | 24 Participants | 16 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 0 Participants | 1 Participants | 1 Participants |
| Pre-ART Plasma Viral Set-point | 3.08 log10 copies/mL STANDARD_DEVIATION 0.469 | 3.13 log10 copies/mL STANDARD_DEVIATION 0.34 | 3.15 log10 copies/mL STANDARD_DEVIATION 0.275 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 17 Participants | 11 Participants |
| Sex: Female, Male Female | 0 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 8 Participants | 21 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 8 |
| other Total, other adverse events | 16 / 17 | 6 / 8 |
| serious Total, serious adverse events | 1 / 17 | 0 / 8 |
Outcome results
Primary
Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs)
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vesatolimod 4 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TESAEs | 0 percentage of participants |
| Vesatolimod 4 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TEAEs | 100.00 percentage of participants |
| Vesatolimod 4/6 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TESAEs | 0 percentage of participants |
| Vesatolimod 4/6 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TEAEs | 75.00 percentage of participants |
| Vesatolimod 6 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TESAEs | 0 percentage of participants |
| Vesatolimod 6 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TEAEs | 100.00 percentage of participants |
| Vesatolimod 6/8 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TESAEs | 33.3 percentage of participants |
| Vesatolimod 6/8 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TEAEs | 100.00 percentage of participants |
| Vesatolimod 8 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TESAEs | 0 percentage of participants |
| Vesatolimod 8 mg | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TEAEs | 100.00 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TESAEs | 0 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) | TEAEs | 75.00 percentage of participants |
Secondary
Change From Baseline in Immune Cell Activation
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)
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 6: Day 1 | -0.6 percentage of cell activation | Standard Deviation 0.7 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 10: Day 2 | 11.1 percentage of cell activation | Standard Deviation 2.72 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 10: Day 4 | 1.0 percentage of cell activation | Standard Deviation 1.6 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 10: Day 4 | 1.7 percentage of cell activation | Standard Deviation 1.99 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 6: Day 4 | 1.5 percentage of cell activation | Standard Deviation 1.53 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 10: Day 14 | 0.8 percentage of cell activation | Standard Deviation 6.77 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 4: Day 1 | 0.4 percentage of cell activation | Standard Deviation 0.58 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 10: Day 1 | 1.5 percentage of cell activation | Standard Deviation 2.82 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg, Baseline | 12.2 percentage of cell activation | Standard Deviation 6.41 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 10: Day 14 | 0.5 percentage of cell activation | Standard Deviation 0.36 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 4: Day 1 | -1.8 percentage of cell activation | Standard Deviation 5.13 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 10: Day 2 | 7.0 percentage of cell activation | Standard Deviation 4.83 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 4: Day 2 | 6.7 percentage of cell activation | Standard Deviation 4.95 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 6: Day 4 | 0.9 percentage of cell activation | Standard Deviation 0.41 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 4: Day 4 | 1.9 percentage of cell activation | Standard Deviation 6.02 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 10: Day 4 | 3.0 percentage of cell activation | Standard Deviation 3.25 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 6: Day 1 | -0.7 percentage of cell activation | Standard Deviation 5.36 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 4: Day 4 | 0.7 percentage of cell activation | Standard Deviation 0.53 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 6: Day 4 | 2.6 percentage of cell activation | Standard Deviation 3.81 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 10: Day 14 | 1.6 percentage of cell activation | Standard Deviation 3.03 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: Day 1 | -0.7 percentage of cell activation | Standard Deviation 5.15 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR, Baseline | 5.4 percentage of cell activation | Standard Deviation 2.43 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: Day 2 | 23.9 percentage of cell activation | Standard Deviation 8.15 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 10: Day 1 | 1.0 percentage of cell activation | Standard Deviation 0.56 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: Day 4 | 2.0 percentage of cell activation | Standard Deviation 2.55 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+, Baseline | 7.5 percentage of cell activation | Standard Deviation 7.04 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: Day 14 | 1.6 percentage of cell activation | Standard Deviation 4.89 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 4: Day 1 | 0.6 percentage of cell activation | Standard Deviation 1.41 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 4: Day 1 | -2.2 percentage of cell activation | Standard Deviation 5.43 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim, Baseline | 5.0 percentage of cell activation | Standard Deviation 2.68 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 4: Day 2 | 0.9 percentage of cell activation | Standard Deviation 0.88 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 4: Day 1 | -1.5 percentage of cell activation | Standard Deviation 1.46 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 4: Day 2 | 4.5 percentage of cell activation | Standard Deviation 7.45 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 4: Day 2 | 1.0 percentage of cell activation | Standard Deviation 2.98 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 4: Day 2 | 1.6 percentage of cell activation | Standard Deviation 1.19 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 4: Day 4 | 0.9 percentage of cell activation | Standard Deviation 1.63 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 4: Day 4 | 1.0 percentage of cell activation | Standard Deviation 3.04 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 6: Day 1 | 1.9 percentage of cell activation | Standard Deviation 2.09 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 10: Day 2 | 2.6 percentage of cell activation | Standard Deviation 0.11 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 6: Day 4 | 6.2 percentage of cell activation | Standard Deviation 6.68 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 6: Day 1 | 0.2 percentage of cell activation | Standard Deviation 2.36 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 10: Day 4 | 0.0 percentage of cell activation | Standard Deviation 1.46 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 10: Day 1 | 5.0 percentage of cell activation | Standard Deviation 7 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 4: Day 4 | 0.8 percentage of cell activation | Standard Deviation 0.56 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 10: Day 2 | 17.2 percentage of cell activation | Standard Deviation 16.49 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 6: Day 4 | 0.9 percentage of cell activation | Standard Deviation 0.95 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 6: Day 1 | 0.5 percentage of cell activation | Standard Deviation 0.41 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 10: Day 14 | 2.7 percentage of cell activation | Standard Deviation 3.14 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 10: Day 1 | 0.5 percentage of cell activation | Standard Deviation 0.61 |
| Vesatolimod 4 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR, Baseline | 2.7 percentage of cell activation | Standard Deviation 0.94 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 6: Day 4 | 0.2 percentage of cell activation | Standard Deviation 1.72 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 10: Day 1 | 1.3 percentage of cell activation | Standard Deviation 1.72 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 10: Day 2 | 2.2 percentage of cell activation | Standard Deviation 5.08 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 10: Day 4 | 3.3 percentage of cell activation | Standard Deviation 3.7 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 10: Day 14 | 0.9 percentage of cell activation | Standard Deviation 2.93 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at ATI Remission | 0.2 percentage of cell activation | Standard Deviation 0.91 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR, Baseline | 2.3 percentage of cell activation | Standard Deviation 1.04 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 4: Day 1 | -0.3 percentage of cell activation | Standard Deviation 0.38 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 4: Day 2 | 0.4 percentage of cell activation | Standard Deviation 1.02 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 4: Day 4 | -0.3 percentage of cell activation | Standard Deviation 0.74 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 6: Day 1 | -0.2 percentage of cell activation | Standard Deviation 0.9 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 6: Day 4 | -0.1 percentage of cell activation | Standard Deviation 1.2 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 10: Day 1 | -0.4 percentage of cell activation | Standard Deviation 0.45 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 10: Day 2 | -0.3 percentage of cell activation | Standard Deviation 0.75 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 10: Day 4 | -0.2 percentage of cell activation | Standard Deviation 1.45 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at Dose 10: Day 14 | 0.1 percentage of cell activation | Standard Deviation 1.16 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD4/CD38/HLADR,Change at ATI Remission | 1.3 percentage of cell activation | Standard Deviation 1.63 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR, Baseline | 5.2 percentage of cell activation | Standard Deviation 2.86 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 4: Day 1 | -0.8 percentage of cell activation | Standard Deviation 1.23 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 4: Day 2 | 0.2 percentage of cell activation | Standard Deviation 2.06 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 4: Day 4 | -0.9 percentage of cell activation | Standard Deviation 1.83 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 6: Day 1 | -1.1 percentage of cell activation | Standard Deviation 1.56 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 6: Day 4 | -0.7 percentage of cell activation | Standard Deviation 2.14 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 10: Day 1 | -1.3 percentage of cell activation | Standard Deviation 1.77 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 10: Day 2 | -1.2 percentage of cell activation | Standard Deviation 2.09 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 10: Day 4 | -1.3 percentage of cell activation | Standard Deviation 2.31 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at Dose 10: Day 14 | 0.0 percentage of cell activation | Standard Deviation 2.81 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD8/CD38/HLADR,Change at ATI Remission Visit | 6.0 percentage of cell activation | Standard Deviation 6.41 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+, Baseline | 6.7 percentage of cell activation | Standard Deviation 6.31 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 4: Day 1 | -0.4 percentage of cell activation | Standard Deviation 3.24 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 4: Day 2 | 0.5 percentage of cell activation | Standard Deviation 2.81 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 4: Day 4 | 0.0 percentage of cell activation | Standard Deviation 5.12 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 6: Day 1 | 0.4 percentage of cell activation | Standard Deviation 4.32 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 6: Day 4 | -1.5 percentage of cell activation | Standard Deviation 4.78 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 10: Day 1 | -1.2 percentage of cell activation | Standard Deviation 4.67 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 10: Day 2 | -2.2 percentage of cell activation | Standard Deviation 5.81 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 10: Day 4 | -1.4 percentage of cell activation | Standard Deviation 5.1 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at Dose 10: Day 14 | -0.4 percentage of cell activation | Standard Deviation 3.92 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56+CD16+,Change at ATI Remission Visit | -1.7 percentage of cell activation | Standard Deviation 1.34 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg, Baseline | 11.3 percentage of cell activation | Standard Deviation 10.37 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 4: Day 1 | -0.7 percentage of cell activation | Standard Deviation 2.72 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 4: Day 2 | -0.8 percentage of cell activation | Standard Deviation 4.1 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 4: Day 4 | -1.1 percentage of cell activation | Standard Deviation 6.5 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 6: Day 1 | -3.0 percentage of cell activation | Standard Deviation 7.89 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 6: Day 4 | -3.0 percentage of cell activation | Standard Deviation 7 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: Day 1 | -3.7 percentage of cell activation | Standard Deviation 7.02 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: Day 2 | -4.2 percentage of cell activation | Standard Deviation 7.94 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: Day 4 | -2.0 percentage of cell activation | Standard Deviation 6.7 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: Day 14 | -2.5 percentage of cell activation | Standard Deviation 8.49 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56dimCD16neg,Change at Dose 10: ATI Remission | -7.3 percentage of cell activation | Standard Deviation 13.15 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim, Baseline | 2.6 percentage of cell activation | Standard Deviation 1.02 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 4: Day 1 | -0.3 percentage of cell activation | Standard Deviation 1.89 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 4: Day 2 | 0.6 percentage of cell activation | Standard Deviation 2.49 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 4: Day 4 | 2.9 percentage of cell activation | Standard Deviation 2.13 |
| Vesatolimod 4/6 mg | Change From Baseline in Immune Cell Activation | CD69+CD56brCD16dim,Change at Dose 6: Day 1 | 1.5 percentage of cell activation | Standard Deviation 2.9 |
Comparison: CD4/CD38/HLADR, Baselinep-value: 0.7469Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 4: Day 1p-value: 0.1207Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 4: Day 2p-value: 0.4113Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 4: Day 4p-value: 0.1113Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 6: Day 1p-value: 0.241Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 6: Day 4p-value: 0.1098Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 10: Day 1p-value: 0.0369Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 10: Day 2p-value: 0.0814Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 10: Day 4p-value: 0.1658Wilcoxon (Mann-Whitney)
Comparison: CD4/CD38/HLADR, Dose 10: Day 14p-value: 0.9431Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Baselinep-value: 0.6514Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 4: Day 1p-value: 0.0821Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 4: Day 2p-value: 0.2353Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 4: Day 4p-value: 0.1779Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 6: Day 1p-value: 0.7491Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 6: Day 4p-value: 0.07Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 10: Day 1p-value: 0.3711Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 10: Day 2p-value: 0.0814Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 10: Day 4p-value: 0.07Wilcoxon (Mann-Whitney)
Comparison: CD8/CD38/HLADR, Dose 10: Day 14p-value: 0.8303Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Baselinep-value: 0.953Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 4: Day 1p-value: 0.1735Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 4: Day 2p-value: 0.2971Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 4: Day 4p-value: 1Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 6: Day 1p-value: 1Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 6: Day 4p-value: 0.3374Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 10: Day 1p-value: 0.7656Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 10: Day 2p-value: 0.0814Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 10: Day 4p-value: 0.3374Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56+CD16+, Dose 10: Day 14p-value: 0.432Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Baselinep-value: 0.8597Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 4: Day 1p-value: 1Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 4: Day 2p-value: 0.0306Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 4: Day 4p-value: 0.8345Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 6: Day 1p-value: 0.9151Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 6: Day 4p-value: 0.1098Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 10: Day 1p-value: 1Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 10: Day 2p-value: 0.0814Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 10: Day 4p-value: 0.4555Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56dimCD16neg, Dose 10: Day 14p-value: 0.6171Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Baselinep-value: 0.0677Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Dose 4: Day 1p-value: 0.4712Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Dose 4: Day 2p-value: 0.6889Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Dose 4: Day 4p-value: 0.1437Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Dose 6: Day 1p-value: 0.7491Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Dose 6: Day 4p-value: 0.07Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Dose 10: Day 1p-value: 0.7656Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Dose 10: Day 2p-value: 0.1752Wilcoxon (Mann-Whitney)
Comparison: CD69+CD56brCD16dim, Dose 10: Day 4p-value: 0.07Wilcoxon (Mann-Whitney)
p-value: 0.2246Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Levels of Serum Cytokines
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)
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Early Study Drug Discontinuation | 31.2 pg/mL | — |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 4: Day 2 | 0.75 pg/mL | Standard Deviation 2.361 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 4: Day 8 | 0.01 pg/mL | Standard Deviation 0.064 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 10: Day 1 | -0.01 pg/mL | Standard Deviation 0.031 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 10: Day 2 | 0.51 pg/mL | Standard Deviation 1.028 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 10: Day 8 | 0.01 pg/mL | Standard Deviation 0.072 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at ATI Remission Visit | -0.03 pg/mL | Standard Deviation 0.059 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Early study drug discontinuation | 0.00 pg/mL | — |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA, Baseline | 2346.1 pg/mL | Standard Deviation 3743.44 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 1: Day 2 | 2797.6 pg/mL | Standard Deviation 2908.21 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 1: Day 8 | -326.9 pg/mL | Standard Deviation 914.43 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 4: Day 1 | 390.4 pg/mL | Standard Deviation 856.29 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 4: Day 2 | 5140.4 pg/mL | Standard Deviation 8692.35 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 4: Day 8 | -63.9 pg/mL | Standard Deviation 1749.75 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 10: Day 1 | -160.9 pg/mL | Standard Deviation 1229.91 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 10: Day 2 | 3790.2 pg/mL | Standard Deviation 6401.27 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 10: Day 8 | -77.6 pg/mL | Standard Deviation 521.52 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at ATI Remission Visit | -161.7 pg/mL | Standard Deviation 1030.42 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Early study drug discontinuation | 222.4 pg/mL | — |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10, Baseline | 161.0 pg/mL | Standard Deviation 82.04 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10, Change at Dose 1: Day 2 | 554.1 pg/mL | Standard Deviation 693.55 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 1: Day 8 | 38.8 pg/mL | Standard Deviation 126.82 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 4: Day 1 | 27.8 pg/mL | Standard Deviation 71.62 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 4: Day 2 | 337.9 pg/mL | Standard Deviation 487.83 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 4: Day 8 | 23.4 pg/mL | Standard Deviation 58.5 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 10: Day 1 | 19.1 pg/mL | Standard Deviation 44.13 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 10: Day 2 | 554.6 pg/mL | Standard Deviation 893.7 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10, Change at Dose 10: Day 8 | 18.1 pg/mL | Standard Deviation 82.14 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at ATI Remission | 47.5 pg/mL | Standard Deviation 48.42 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Early Study Drug Discontinuation | 0.7 pg/mL | — |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC, Baseline | 71.8 pg/mL | Standard Deviation 108.1 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC, Change at Dose 1: Day 2 | 50.4 pg/mL | Standard Deviation 80.46 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 1: Day 8 | 11.5 pg/mL | Standard Deviation 34.78 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC, Change at Dose 4: Day 1 | 8.0 pg/mL | Standard Deviation 25.97 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 4: Day 2 | 48.0 pg/mL | Standard Deviation 78.14 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC, Change at Dose 4: Day 8 | 2.0 pg/mL | Standard Deviation 24.2 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 10: Day 1 | -1.6 pg/mL | Standard Deviation 19.11 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 10: Day 2 | 69.1 pg/mL | Standard Deviation 181.55 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 10: Day 8 | 2.2 pg/mL | Standard Deviation 12.19 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at ATI Remission | 19.1 pg/mL | Standard Deviation 20.44 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a, Baseline | 0.02 pg/mL | Standard Deviation 0.036 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 1: Day 2 | 0.41 pg/mL | Standard Deviation 0.834 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 1: Day 8 | 0.14 pg/mL | Standard Deviation 0.447 |
| Vesatolimod 4 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 4: Day 1 | -0.01 pg/mL | Standard Deviation 0.03 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a, Baseline | 0.05 pg/mL | Standard Deviation 0.075 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at ATI Remission | 26.2 pg/mL | Standard Deviation 92.41 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 1: Day 2 | -0.01 pg/mL | Standard Deviation 0.073 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 4: Day 2 | -8.9 pg/mL | Standard Deviation 33.81 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 1: Day 8 | 0.04 pg/mL | Standard Deviation 0.129 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10, Baseline | 178.5 pg/mL | Standard Deviation 103.5 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 4: Day 1 | 0.10 pg/mL | Standard Deviation 0.358 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 10: Day 2 | -1.0 pg/mL | Standard Deviation 27.68 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 4: Day 2 | -0.01 pg/mL | Standard Deviation 0.065 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10, Change at Dose 1: Day 2 | -23.9 pg/mL | Standard Deviation 52.24 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 4: Day 8 | -0.03 pg/mL | Standard Deviation 0.077 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC, Baseline | 206.3 pg/mL | Standard Deviation 329.55 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 10: Day 1 | -0.03 pg/mL | Standard Deviation 0.056 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 1: Day 8 | 34.5 pg/mL | Standard Deviation 182.93 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 10: Day 2 | -0.02 pg/mL | Standard Deviation 0.055 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC, Change at Dose 4: Day 8 | 5.0 pg/mL | Standard Deviation 27.98 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at Dose 10: Day 8 | -0.04 pg/mL | Standard Deviation 0.065 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 4: Day 1 | -25.3 pg/mL | Standard Deviation 46.15 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IFN-a,Change at ATI Remission Visit | 0.17 pg/mL | Standard Deviation 0.301 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC, Change at Dose 1: Day 2 | -13.9 pg/mL | Standard Deviation 42.68 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 4: Day 2 | -13.8 pg/mL | Standard Deviation 78.1 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA, Baseline | 882.9 pg/mL | Standard Deviation 306.75 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at ATI Remission | 39.6 pg/mL | Standard Deviation 88.54 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 1: Day 2 | 94.8 pg/mL | Standard Deviation 190.53 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 4: Day 8 | -59.0 pg/mL | Standard Deviation 58.04 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 1: Day 8 | 1004.9 pg/mL | Standard Deviation 2432.36 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 1: Day 8 | -10.4 pg/mL | Standard Deviation 44.02 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 4: Day 1 | 42.2 pg/mL | Standard Deviation 227.9 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 10: Day 1 | -22.8 pg/mL | Standard Deviation 54.29 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 4: Day 2 | 186.4 pg/mL | Standard Deviation 449.94 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 10: Day 1 | -8.4 pg/mL | Standard Deviation 33.91 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 4: Day 8 | -143.5 pg/mL | Standard Deviation 226.83 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10,Change at Dose 10: Day 2 | -17.5 pg/mL | Standard Deviation 50.94 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 10: Day 1 | 563.9 pg/mL | Standard Deviation 1201.78 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC, Change at Dose 4: Day 1 | -25.4 pg/mL | Standard Deviation 65.76 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 10: Day 2 | 14.1 pg/mL | Standard Deviation 467.9 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IP-10, Change at Dose 10: Day 8 | -51.1 pg/mL | Standard Deviation 57.23 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at Dose 10: Day 8 | -13.9 pg/mL | Standard Deviation 308.8 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | ITAC,Change at Dose 10: Day 8 | -7.4 pg/mL | Standard Deviation 22.5 |
| Vesatolimod 4/6 mg | Change From Baseline in Levels of Serum Cytokines | IL-1RA,Change at ATI Remission Visit | 491.1 pg/mL | Standard Deviation 306.12 |
Comparison: IFN-a, Baselinep-value: 0.34Wilcoxon (Mann-Whitney)
Comparison: IFN-a, Dose 1: Day 2p-value: 0.11Wilcoxon (Mann-Whitney)
Comparison: IFN-a, Dose 1: Day 8p-value: 0.81Wilcoxon (Mann-Whitney)
Comparison: IFN-a, Dose 4: Day 1p-value: 0.83Wilcoxon (Mann-Whitney)
Comparison: IFN-a, Dose 4: Day 2p-value: 0.12Wilcoxon (Mann-Whitney)
Comparison: IFN-a, Dose 4: Day 8p-value: 0.45Wilcoxon (Mann-Whitney)
Comparison: IFN-a, Dose 10: Day 1p-value: 0.25Wilcoxon (Mann-Whitney)
Comparison: IFN-a, Dose 10: Day 2p-value: 0.053Wilcoxon (Mann-Whitney)
Comparison: IFN-a, Dose 10: Day 8p-value: 0.16Wilcoxon (Mann-Whitney)
Comparison: IFN-a, ATI Remission Visitp-value: 0.27Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Baselinep-value: 0.35Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Dose 1: Day 2p-value: 0.013Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Dose 1: Day 8p-value: 0.15Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Dose 4: Day 1p-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Dose 4: Day 2p-value: 0.003Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Dose 4: Day 8p-value: 0.49Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Dose 10: Day 1p-value: 0.25Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Dose 10: Day 2p-value: 0.055Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, Dose 10: Day 8p-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: IL-1RA, ATI Remission Visitp-value: 0.39Wilcoxon (Mann-Whitney)
Comparison: IP-10, Baselinep-value: 0.75Wilcoxon (Mann-Whitney)
Comparison: IP-10, Dose 1: Day 2p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: IP-10, Dose 1: Day 8p-value: 0.69Wilcoxon (Mann-Whitney)
Comparison: IP-10, Dose 4: Day 1p-value: 0.15Wilcoxon (Mann-Whitney)
Comparison: IP-10, Dose 4: Day 2p-value: 0.018Wilcoxon (Mann-Whitney)
Comparison: IP-10, Dose 4: Day 8p-value: 0.03Wilcoxon (Mann-Whitney)
Comparison: IP-10, Dose 10: Day 1p-value: 0.087Wilcoxon (Mann-Whitney)
Comparison: IP-10, Dose 10: Day 2p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: IP-10, Dose 10: Day 8p-value: 0.066Wilcoxon (Mann-Whitney)
Comparison: IP-10, ATI Remissionp-value: 0.86Wilcoxon (Mann-Whitney)
Comparison: ITAC, Baselinep-value: 0.19Wilcoxon (Mann-Whitney)
Comparison: ITAC, Dose 1: Day 2p-value: 0.021Wilcoxon (Mann-Whitney)
Comparison: ITAC, Dose 1: Day 8p-value: 0.31Wilcoxon (Mann-Whitney)
Comparison: ITAC, Dose 4: Day 1p-value: 0.1Wilcoxon (Mann-Whitney)
Comparison: ITAC, Dose 4: Day 2p-value: 0.018Wilcoxon (Mann-Whitney)
Comparison: ITAC, Dose 4: Day 8p-value: 0.69Wilcoxon (Mann-Whitney)
Comparison: ITAC, Dose 10: Day 1p-value: 0.46Wilcoxon (Mann-Whitney)
Comparison: ITAC, Dose 10: Day 2p-value: 0.21Wilcoxon (Mann-Whitney)
Comparison: ITAC, Dose 10: Day 8p-value: 0.67Wilcoxon (Mann-Whitney)
Comparison: ITAC, ATI Remissionp-value: 0.6Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 4: Day 1 | -0.03 Log10 copies/mL | Standard Deviation 0.111 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 1: Day 8 | 0.05 Log10 copies/mL | Standard Deviation 0.212 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 2: Day 1 | 0.09 Log10 copies/mL | Standard Deviation 0.372 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 2: Day 8 | -0.03 Log10 copies/mL | Standard Deviation 0.111 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 3: Day 1 | -0.03 Log10 copies/mL | Standard Deviation 0.111 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 3: Day 8 | -0.03 Log10 copies/mL | Standard Deviation 0.111 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 1: Day 2 | -0.01 Log10 copies/mL | Standard Deviation 0.027 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 4: Day 2 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 4: Day 4 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 4: Day 8 | -0.03 Log10 copies/mL | Standard Deviation 0.111 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 5: Day 1 | -0.03 Log10 copies/mL | Standard Deviation 0.111 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 5: Day 8 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 6: Day 1 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 6: Day 4 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 6: Day 8 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 7: Day 1 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 7: Day 8 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 8: Day 1 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 8: Day 8 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 9: Day 1 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 9: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 1 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 2 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 4 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 8 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 14 | -0.03 Log10 copies/mL | Standard Deviation 0.115 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 9: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 1: Day 2 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 6: Day 4 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 1: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 2: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 6: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 2: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 9: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 3: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 7: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 3: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 4 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 4: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 7: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 4: Day 2 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 4: Day 4 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 8: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 4: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 14 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 5: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 8: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 5: Day 8 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 10: Day 2 | 0.00 Log10 copies/mL | Standard Deviation 0 |
| Vesatolimod 4/6 mg | Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 | Change at Dose 6: Day 1 | 0.00 Log10 copies/mL | Standard Deviation 0 |
Comparison: Dose 1: Day 2p-value: 0.55Wilcoxon (Mann-Whitney)
Comparison: Dose 1: Day 8p-value: 0.54Wilcoxon (Mann-Whitney)
Comparison: Dose 2: Day 1p-value: 0.54Wilcoxon (Mann-Whitney)
Comparison: Dose 2: Day 8p-value: 0.54Wilcoxon (Mann-Whitney)
Comparison: Dose 3: Day 1p-value: 0.54Wilcoxon (Mann-Whitney)
Comparison: Dose 3: Day 8p-value: 0.57Wilcoxon (Mann-Whitney)
Comparison: Dose 4: Day 1p-value: 0.54Wilcoxon (Mann-Whitney)
Comparison: Dose 4: Day 2p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 4: Day 4p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 4: Day 8p-value: 0.61Wilcoxon (Mann-Whitney)
Comparison: Dose 5: Day 1p-value: 0.54Wilcoxon (Mann-Whitney)
Comparison: Dose 5: Day 8p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 6: Day 1p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 6: Day 4p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 6: Day 8p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 7: Day 1p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 7 - Day 8p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 8: Day 1p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 8: Day 8p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 9: Day 1p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 9: Day 8p-value: 1Wilcoxon (Mann-Whitney)
Comparison: Dose 10: Day 1p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 10: Day 2p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 10: Day 4p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 10: Day 8p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Dose 10: Day 14p-value: 0.52Wilcoxon (Mann-Whitney)
Secondary
Change in Plasma Viral Load Set-Point Following ATI
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)
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vesatolimod 4 mg | Change in Plasma Viral Load Set-Point Following ATI | -0.37 Log10 copies/mL |
| Vesatolimod 4/6 mg | Change in Plasma Viral Load Set-Point Following ATI | -0.28 Log10 copies/mL |
p-value: 0.78Wilcoxon (Mann-Whitney)
Secondary
Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood
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)
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 1: Day 2 | 19.53 fold change | Standard Deviation 15.548 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Early Study Drug Discontinuation | 1.14 fold change | — |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 1: Day 2 | 6.83 fold change | Standard Deviation 4.225 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 4: Day 2 | 9.91 fold change | Standard Deviation 8.061 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 4: Day 1 | 2.21 fold change | Standard Deviation 2.087 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 4: Day 1 | 3.35 fold change | Standard Deviation 5.212 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 4: Day 2 | 7.44 fold change | Standard Deviation 4.65 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 10: Day 2 | 10.29 fold change | Standard Deviation 8.862 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 10: Day 1 | 1.47 fold change | Standard Deviation 0.665 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 4: Day 2 | 19.09 fold change | Standard Deviation 15.113 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 10: Day 2 | 6.83 fold change | Standard Deviation 5.189 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 10: Day 1 | 1.59 fold change | Standard Deviation 0.844 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Early Study Drug Discontinuation | 1.08 fold change | — |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 1: Day 2 | 9.36 fold change | Standard Deviation 6.873 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 4: Day 1 | 2.98 fold change | Standard Deviation 4.65 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 10: Day 1 | 1.62 fold change | Standard Deviation 0.742 |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Early Study Drug Discontinuation | 1.06 fold change | — |
| Vesatolimod 4 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 10: Day 2 | 19.71 fold change | Standard Deviation 20.209 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 1: Day 2 | 1.06 fold change | Standard Deviation 0.249 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 4: Day 1 | 1.17 fold change | Standard Deviation 0.312 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 4: Day 2 | 3.49 fold change | Standard Deviation 6.957 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 10: Day 1 | 1.03 fold change | Standard Deviation 0.226 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | MX1, Dose 10: Day 2 | 0.98 fold change | Standard Deviation 0.232 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 1: Day 2 | 1.06 fold change | Standard Deviation 0.32 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 4: Day 1 | 1.24 fold change | Standard Deviation 0.343 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 4: Day 2 | 8.41 fold change | Standard Deviation 20.782 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 10: Day 1 | 1.02 fold change | Standard Deviation 0.223 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | ISG15, Dose 10: Day 2 | 1.02 fold change | Standard Deviation 0.366 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 1: Day 2 | 1.07 fold change | Standard Deviation 0.285 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 4: Day 1 | 1.13 fold change | Standard Deviation 0.395 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 4: Day 2 | 2.62 fold change | Standard Deviation 4.676 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 10: Day 1 | 1.03 fold change | Standard Deviation 0.218 |
| Vesatolimod 4/6 mg | Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood | OAS-1, Dose 10: Day 2 | 1.04 fold change | Standard Deviation 0.162 |
Comparison: ISG15, Dose 1: Day 2p-value: 0.002Wilcoxon (Mann-Whitney)
Comparison: ISG15, Dose 4: Day 1p-value: 0.58Wilcoxon (Mann-Whitney)
Comparison: ISG15, Dose 4: Day 2p-value: 0.009Wilcoxon (Mann-Whitney)
p-value: 0.031Wilcoxon (Mann-Whitney)
Comparison: ISG15, Dose 10: Day 2p-value: 0.001Wilcoxon (Mann-Whitney)
Comparison: OAS-1, Dose 1: Day 2p-value: 0.003Wilcoxon (Mann-Whitney)
Comparison: OAS-1, Dose 4: Day 1p-value: 0.057Wilcoxon (Mann-Whitney)
Comparison: OAS-1, Dose 4: Day 2p-value: 0.009Wilcoxon (Mann-Whitney)
Comparison: OAS-1, Dose 10: Day 1p-value: 0.057Wilcoxon (Mann-Whitney)
Comparison: OAS-1, Dose 10: Day 2p-value: 0.005Wilcoxon (Mann-Whitney)
Comparison: MX1, Dose 1: Day 2p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: MX1, Dose 4: Day 1p-value: 0.17Wilcoxon (Mann-Whitney)
Comparison: MX1, Dose 4: Day 2p-value: 0.003Wilcoxon (Mann-Whitney)
p-value: 0.1Wilcoxon (Mann-Whitney)
Comparison: MX1, Dose 10: Day 2p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Peak HIV-1 Viral Load During Period 2
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vesatolimod 4 mg | Peak HIV-1 Viral Load During Period 2 | 4.21 Log10 copies/mL |
| Vesatolimod 4/6 mg | Peak HIV-1 Viral Load During Period 2 | 3.97 Log10 copies/mL |
p-value: 0.67Wilcoxon (Mann-Whitney)
Secondary
Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod
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.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vesatolimod 4 mg | Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod | 7149.6 pg/mL | Standard Deviation 7662.17 |
Secondary
PK Parameter: %AUCexp of Vesatolimod
%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.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vesatolimod 4 mg | PK Parameter: %AUCexp of Vesatolimod | 22.4 Percentage of AUC | Standard Deviation 7.9 |
Secondary
PK Parameter: AUCinf of Vesatolimod
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.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vesatolimod 4 mg | PK Parameter: AUCinf of Vesatolimod | 60040.3 hour*pg/mL | Standard Deviation 59280.72 |
Secondary
PK Parameter: AUClast of Vesatolimod
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.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vesatolimod 4 mg | PK Parameter: AUClast of Vesatolimod | 49323.5 hour*pg/ml | Standard Deviation 48542.34 |
Secondary
PK Parameter: Tmax of Vesatolimod
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.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Vesatolimod 4 mg | PK Parameter: Tmax of Vesatolimod | 2.00 hour |
Secondary
Time to Virologic Rebound
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Vesatolimod 4 mg | Time to Virologic Rebound | ≥ 50 Copies/mL | 4.3 weeks |
| Vesatolimod 4 mg | Time to Virologic Rebound | ≥ 200 Copies/mL | 5.1 weeks |
| Vesatolimod 4/6 mg | Time to Virologic Rebound | ≥ 50 Copies/mL | 4.0 weeks |
| Vesatolimod 4/6 mg | Time to Virologic Rebound | ≥ 200 Copies/mL | 4.1 weeks |
Comparison: ≥ 50 Copies/mLp-value: 0.035Log Rank
Comparison: ≥ 200 Copies/mLp-value: 0.024Log Rank