HIV Infections
Conditions
Keywords
Human immunodeficiency virus, Proof of concept, Antiviral Agents, Virus Diseases
Brief summary
The purpose of this study is to evaluate the safety, tolerability, ability of VH4524184 when given alone to reduce the amount of HIV (viral load) in people with HIV-1 infection who have never received antiretroviral therapy (treatment-naïve). Data from this study will be used to decide how VH4524184 can be best included in a full-treatment regimen for HIV-1 in the future.
Interventions
DRUGVH4524184
VH4524184 was administered as tablets orally at Day 1.
DRUGMatching Placebo
VH4524184 Matching Placebo was administered as tablets orally at Day 1.
DRUGAntiretroviral therapy
Antiretroviral therapy was administered as available and as per investigator's recommendation.
Sponsors
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Data will be collected in a double-blind manner during the monotherapy phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be 18 to 65 years of age inclusive at the time of signing the informed consent. * Participants who are overtly healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * Positive HIV antibody test * Documented HIV infection and Screening plasma HIV-1 RNA ≥ 3,000 copies/mL. A single repeat of this test is allowed within a single Screening period to determine eligibility. * Screening CD4+ T-cell count ≥200 cells/mm3 * Treatment-naïve: No antiretrovirals (ARVs, in combination or monotherapy) received after the diagnosis of HIV-1 infection. * HIV Pre-exposure or post-exposure prophylaxis: No prior use of any INSTI (including cabotegravir) for HIV pre-exposure or post-exposure prophylaxis. * Body weight ≥50.0 kg (110 lbs.) for men and ≥45.0 kg (99 lbs) for women and BMI within the range 18.5-31.0 kg/m2 (inclusive - applies to males and females). * A participant of childbearing potential must have a negative serum hCG test at screening, and negative urine hCG test at Day 1, before the first dose of study intervention. * If a urine test cannot be confirmed as negative (e.g. ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. * The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease risk for inclusion of a female with an early undetected pregnancy. * Capable of giving signed informed consent * Participant must be willing and able to start standard-of-care ART as selected with the investigator on Study Day 10.
Exclusion criteria
* Participants with primary HIV infection. Any evidence of an active CDC Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the study. Untreated syphilis infection \[positive RPR at screen\] without documentation of treatment. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies * Any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant. * Any history of significant underlying psychiatric disorder, or a clinical assessment of suicidality based on the responses on the eCSSRS. * Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (\>6 months) outpatient treatment. * Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome or sudden cardiac death. Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration. * Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing. Specific medications listed in Section 6.9.1 may be allowed. * Participants who require concomitant medications known to be associated with a prolonged QTc. * Participants receiving any protocol-prohibited medication(s) and who are unwilling or unable to switch to an alternate medication). * The participant has ever received an investigational HIV vaccine (immunotherapeutic or immunomodulatory). * Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study intervention. * Participation in the study would result in donation of blood in excess of 500 mL within 56 days. * Exposure to more than four new investigational drugs or vaccines within 12 months prior to the first dosing day. * Current enrollment or past participation within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research. Diagnostic Assessments * Presence of HBsAg or HBcAb at screening * Positive Hepatitis C antibody test result at Screening * Positive Hepatitis C RNA test result at Screening. * Creatinine clearance (eGFR) of \< 60 mL/min/1.73 m2 using CKD-EPI equation (2021).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) | At Day 10 | Plasma samples were collected for the quantitative analysis of plasma HIV-1 RNA. The maximum change from baseline was calculated by determining the largest change from baseline value across all assessment timepoints during the monotherapy period. This is identified by subtracting the lowest post-dose visit value up to Day 10 (inclusive) from the baseline value. The baseline was defined as the most recent pre-dose assessment with a valid, non-missing value, including measurements from any unscheduled visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monotherapy and Follow-up: Number of Participants With AEs by Severity | Day 1 to Day 38 | The severity was assessed using The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.1 where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening and Grade 5 = Death. |
| Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation | Day 1 to Day 7 | — |
| Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38 | Blood samples were collected at the indicated timepoints. |
| Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38 | Blood samples were collected at the indicated timepoints. |
| Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38 | Blood samples were collected at the indicated timepoints. |
| Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | From Baseline (Day 1) and up to Day 38 | Liver panel parameters assessed were: ALT, AST, ALP, bilirubin. The parameters were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase is defined as an increase in grade relative to baseline grade. |
| Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | From Baseline (Day 1) and up to Day 38 | Participants are categorized based on changes in their liver panel laboratory parameters (protein) to 'Low,' 'Normal,' or 'High,' unless there is no change in their initial category. Participants whose lab values remain unchanged (e.g., 'High' to 'High') or whose values return to normal are recorded in the 'To Normal or No Change' category. Participants may be counted in both the 'To Low' and 'To High' categories if their values fluctuate between these states. As a result, the percentages may exceed 100% due to dual categorization. Participants with a missing baseline value are assumed to have a normal baseline value. |
| Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE) | Day 1 to Day 38 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Any AEs = occurrence of the symptom regardless of intensity grade. |
| Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184 | At Day 1 and Day 7 | Blood samples were collected at indicated time points for PK analysis of VH4524184. |
| Monotherapy: Plasma Concentration of VH4524184 at Day 10 | At Day 10 | Blood samples was collected at indicated time point for PK analysis of VH4524184. |
| Monotherapy: Correlation of VH4524184 Cmax With Maximum Plasma HIV-1 RNA Log 10 Change From Baseline Through Day 10 | From Day 1 to Day 10 | Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value. Change from baseline is defined as post-dose visit value minus baseline value. Statistical analysis for relationship between PK parameter (Cmax) and PD measure (change from baseline in logarithm to base 10 (log10) values for maximum plasma HIV-1 RNA) were explored using an Emax non-linear mixed-effects model. The model parameters estimated were maximum response (Emax) which is defined as the maximum change (at infinite exposure) and EC50 which defines the PK parameter value that attains 50 percent (%) of the maximal effect |
| Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance | At Baseline (Day 1) and Day 10 | Plasma samples were collected to assess treatment emergent Genotypic Resistance. |
| Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance | At Baseline (Day 1) and Day 10 | Plasma samples were collected to assess treatment emergent Phenotypic Resistance. |
| Monotherapy: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10 | At Day 10 compared to Baseline (Day 1) | Blood samples were collected for assessment of T-cells subsets (CD4+ T-cells count) by flow cytometry at Day 10 compared to Baseline. |
| Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184 | At Day 1 and Day 7 | Blood samples were collected at indicated time points for Pharmacokinetic (PK) analysis of VH4524184. |
Countries
Argentina, Canada, Italy, Spain, United States
Participant flow
Pre-assignment details
Part 2 of the study was optional and was not selected for enrollment following interim analysis of part 1 based on Pharmacokinetic/Pharmacodynamic modelling and preliminary clinical data.
Participants by arm
| Arm | Count |
|---|---|
| VH4524184 Dose 1 Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38. | 6 |
| VH4524184 Dose 2 Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38. | 6 |
| VH4524184 Dose 3 Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38. | 7 |
| Placebo Participants received matching Placebo to the study intervention on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38. | 3 |
| Total | 22 |
Baseline characteristics
| Characteristic | VH4524184 Dose 1 | VH4524184 Dose 2 | VH4524184 Dose 3 | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 34.2 YEARS STANDARD_DEVIATION 10.61 | 36.7 YEARS STANDARD_DEVIATION 16.18 | 33.9 YEARS STANDARD_DEVIATION 12.52 | 29.3 YEARS STANDARD_DEVIATION 3.79 | 34.1 YEARS STANDARD_DEVIATION 11.85 |
| Race/Ethnicity, Customized All Other Races | 6 Participants | 6 Participants | 7 Participants | 3 Participants | 22 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 6 Participants | 3 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 3 |
| other Total, other adverse events | 2 / 6 | 3 / 6 | 3 / 7 | 2 / 3 | 4 / 6 | 5 / 6 | 4 / 7 | 2 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 3 |
Outcome results
Primary
Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA)
Plasma samples were collected for the quantitative analysis of plasma HIV-1 RNA. The maximum change from baseline was calculated by determining the largest change from baseline value across all assessment timepoints during the monotherapy period. This is identified by subtracting the lowest post-dose visit value up to Day 10 (inclusive) from the baseline value. The baseline was defined as the most recent pre-dose assessment with a valid, non-missing value, including measurements from any unscheduled visits.
Time frame: At Day 10
Population: Analysis was performed on Full Analysis Set (FAS), which included all randomized participants who received at least 1 full dose of study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) | -1.17 Copies per milliliter (copies/mL) | Standard Deviation 0.46 |
| VH4524184 Dose 2 | Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) | -2.15 Copies per milliliter (copies/mL) | Standard Deviation 0.254 |
| VH4524184 Dose 3 | Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) | -2.31 Copies per milliliter (copies/mL) | Standard Deviation 0.463 |
| Placebo | Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) | -0.28 Copies per milliliter (copies/mL) | Standard Deviation 0.37 |
Secondary
Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin
Blood samples were collected at the indicated timepoints.
Time frame: At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38
Population: Analysis was performed on Safety Set. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Baseline (Day 1) | 8.2935 Micromoles per liter (μmol/L) | Standard Deviation 5.93914 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 4 | 1.4820 Micromoles per liter (μmol/L) | Standard Deviation 5.38437 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 31 | -0.2052 Micromoles per liter (μmol/L) | Standard Deviation 7.41576 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 7 | -1.5105 Micromoles per liter (μmol/L) | Standard Deviation 4.25706 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 2 | 1.0545 Micromoles per liter (μmol/L) | Standard Deviation 3.03093 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 38 | 1.7100 Micromoles per liter (μmol/L) | Standard Deviation 5.46665 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 24 | 1.7100 Micromoles per liter (μmol/L) | Standard Deviation 6.10927 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 17 | 0.7980 Micromoles per liter (μmol/L) | Standard Deviation 7.47774 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 10 | 2.2515 Micromoles per liter (μmol/L) | Standard Deviation 6.11541 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Baseline (Day 1) | 5.6145 Micromoles per liter (μmol/L) | Standard Deviation 3.21992 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 31 | 0.0285 Micromoles per liter (μmol/L) | Standard Deviation 1.40768 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 2 | 0.2565 Micromoles per liter (μmol/L) | Standard Deviation 1.32787 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 38 | -0.1712 Micromoles per liter (μmol/L) | Standard Deviation 3.59512 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 4 | 0.8550 Micromoles per liter (μmol/L) | Standard Deviation 2.93204 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 7 | 2.1660 Micromoles per liter (μmol/L) | Standard Deviation 2.2023 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 10 | 0.7695 Micromoles per liter (μmol/L) | Standard Deviation 3.53892 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 17 | 0.1368 Micromoles per liter (μmol/L) | Standard Deviation 3.23863 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 24 | 0.2280 Micromoles per liter (μmol/L) | Standard Deviation 3.65583 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 2 | 1.1481 Micromoles per liter (μmol/L) | Standard Deviation 1.75421 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 31 | 0.3909 Micromoles per liter (μmol/L) | Standard Deviation 2.62828 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 10 | 0.3176 Micromoles per liter (μmol/L) | Standard Deviation 2.2802 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 24 | 1.3436 Micromoles per liter (μmol/L) | Standard Deviation 3.54789 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 17 | 0.4641 Micromoles per liter (μmol/L) | Standard Deviation 3.39097 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 4 | 1.6856 Micromoles per liter (μmol/L) | Standard Deviation 3.71694 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 38 | 0.2931 Micromoles per liter (μmol/L) | Standard Deviation 1.14163 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 7 | -0.8306 Micromoles per liter (μmol/L) | Standard Deviation 2.637 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Baseline (Day 1) | 5.9117 Micromoles per liter (μmol/L) | Standard Deviation 3.2141 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 38 | -3.1923 Micromoles per liter (μmol/L) | Standard Deviation 3.60425 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Baseline (Day 1) | 8.0370 Micromoles per liter (μmol/L) | Standard Deviation 5.75333 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 2 | -0.7410 Micromoles per liter (μmol/L) | Standard Deviation 4.86174 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 4 | -3.2490 Micromoles per liter (μmol/L) | Standard Deviation 5.08132 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 7 | -1.8813 Micromoles per liter (μmol/L) | Standard Deviation 5.60653 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 17 | 1.7670 Micromoles per liter (μmol/L) | Standard Deviation 4.44052 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 24 | -0.5130 Micromoles per liter (μmol/L) | Standard Deviation 2.68748 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 31 | 0.8550 Micromoles per liter (μmol/L) | Standard Deviation 4.42292 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin | Day 10 | -3.0210 Micromoles per liter (μmol/L) | Standard Deviation 3.16389 |
Secondary
Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein
Blood samples were collected at the indicated timepoints.
Time frame: At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38
Population: Analysis was performed on Safety Set. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 31 | 0.4 Grams per liter | Standard Deviation 4.56 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Baseline (Day 1) | 76.5 Grams per liter | Standard Deviation 4.55 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 38 | 0.5 Grams per liter | Standard Deviation 2.26 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 7 | 2.0 Grams per liter | Standard Deviation 3.63 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 24 | 0.8 Grams per liter | Standard Deviation 3.06 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 2 | 2.8 Grams per liter | Standard Deviation 3.6 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 17 | 1.2 Grams per liter | Standard Deviation 3.25 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 10 | 2.2 Grams per liter | Standard Deviation 2.4 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 4 | 4.3 Grams per liter | Standard Deviation 4.37 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 10 | -0.7 Grams per liter | Standard Deviation 3.14 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 17 | 0.4 Grams per liter | Standard Deviation 2.3 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Baseline (Day 1) | 75.5 Grams per liter | Standard Deviation 3.39 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 24 | 0.3 Grams per liter | Standard Deviation 4.46 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 38 | -1.3 Grams per liter | Standard Deviation 4.68 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 4 | 1.5 Grams per liter | Standard Deviation 2.66 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 7 | -1.3 Grams per liter | Standard Deviation 2.34 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 31 | -0.2 Grams per liter | Standard Deviation 5.23 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 2 | 2.2 Grams per liter | Standard Deviation 3.31 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 38 | -1.4 Grams per liter | Standard Deviation 4.35 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Baseline (Day 1) | 77.1 Grams per liter | Standard Deviation 5.49 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 2 | 0.7 Grams per liter | Standard Deviation 3.3 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 4 | 2.1 Grams per liter | Standard Deviation 2.97 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 7 | -1.9 Grams per liter | Standard Deviation 3.89 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 10 | 1.6 Grams per liter | Standard Deviation 2.64 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 17 | 0.1 Grams per liter | Standard Deviation 5.21 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 24 | 0.6 Grams per liter | Standard Deviation 4.43 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 31 | -0.9 Grams per liter | Standard Deviation 3.8 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 24 | 2.0 Grams per liter | Standard Deviation 3 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 10 | 0.3 Grams per liter | Standard Deviation 2.08 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 7 | -1.0 Grams per liter | Standard Deviation 1 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Baseline (Day 1) | 70.0 Grams per liter | Standard Deviation 5.57 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 31 | 8.3 Grams per liter | Standard Deviation 4.51 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 4 | 2.0 Grams per liter | Standard Deviation 1 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 2 | 5.7 Grams per liter | Standard Deviation 1.53 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 17 | 7.3 Grams per liter | Standard Deviation 4.16 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein | Day 38 | 2.0 Grams per liter | Standard Deviation 4.58 |
Secondary
Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP)
Blood samples were collected at the indicated timepoints.
Time frame: At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38
Population: Analysis was performed on Safety Set. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Baseline (Day 1) | 25.5 International units per liter (IU/L) | Standard Deviation 15.35 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 31 | -2.8 International units per liter (IU/L) | Standard Deviation 10.31 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 38 | -4.7 International units per liter (IU/L) | Standard Deviation 14.05 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 4 | 2.2 International units per liter (IU/L) | Standard Deviation 4.54 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 17 | 22.0 International units per liter (IU/L) | Standard Deviation 47.41 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 38 | -2.8 International units per liter (IU/L) | Standard Deviation 8.26 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 10 | 4.5 International units per liter (IU/L) | Standard Deviation 5.79 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 31 | 5.2 International units per liter (IU/L) | Standard Deviation 3.9 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 17 | 4.5 International units per liter (IU/L) | Standard Deviation 5.09 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Baseline (Day 1) | 29.7 International units per liter (IU/L) | Standard Deviation 24.64 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Baseline (Day 1) | 81.3 International units per liter (IU/L) | Standard Deviation 32.51 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 31 | -0.8 International units per liter (IU/L) | Standard Deviation 6.3 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 17 | 6.7 International units per liter (IU/L) | Standard Deviation 15.1 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 2 | -1.3 International units per liter (IU/L) | Standard Deviation 6.65 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 4 | 2.5 International units per liter (IU/L) | Standard Deviation 9.18 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 24 | 1.2 International units per liter (IU/L) | Standard Deviation 8.01 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 10 | 4.2 International units per liter (IU/L) | Standard Deviation 3.92 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 4 | 2.2 International units per liter (IU/L) | Standard Deviation 3.06 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 24 | 3.2 International units per liter (IU/L) | Standard Deviation 2.86 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 7 | 0.2 International units per liter (IU/L) | Standard Deviation 3.25 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 24 | -1.7 International units per liter (IU/L) | Standard Deviation 6.15 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 7 | -0.3 International units per liter (IU/L) | Standard Deviation 3.67 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 2 | 3.3 International units per liter (IU/L) | Standard Deviation 9.14 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 38 | 4.5 International units per liter (IU/L) | Standard Deviation 3.51 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 7 | 3.7 International units per liter (IU/L) | Standard Deviation 6.5 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 10 | 9.7 International units per liter (IU/L) | Standard Deviation 17.82 |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 2 | 0.0 International units per liter (IU/L) | Standard Deviation 4.2 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 10 | -6.2 International units per liter (IU/L) | Standard Deviation 8.47 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 4 | -0.2 International units per liter (IU/L) | Standard Deviation 3.13 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 17 | -9.0 International units per liter (IU/L) | Standard Deviation 5.83 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 24 | -4.3 International units per liter (IU/L) | Standard Deviation 6.59 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 2 | 2.5 International units per liter (IU/L) | Standard Deviation 6.69 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 31 | -3.0 International units per liter (IU/L) | Standard Deviation 4.2 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 10 | -5.5 International units per liter (IU/L) | Standard Deviation 5.82 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 38 | -4.7 International units per liter (IU/L) | Standard Deviation 5.54 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 2 | 1.3 International units per liter (IU/L) | Standard Deviation 2.5 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Baseline (Day 1) | 70.3 International units per liter (IU/L) | Standard Deviation 15.76 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 24 | -0.2 International units per liter (IU/L) | Standard Deviation 5.19 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 17 | -7.0 International units per liter (IU/L) | Standard Deviation 6.24 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Baseline (Day 1) | 26.0 International units per liter (IU/L) | Standard Deviation 9.27 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 24 | 1.2 International units per liter (IU/L) | Standard Deviation 12.22 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 31 | 0.2 International units per liter (IU/L) | Standard Deviation 7.31 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 17 | 0.0 International units per liter (IU/L) | Standard Deviation 3.74 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 38 | -2.5 International units per liter (IU/L) | Standard Deviation 9.16 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 4 | 0.5 International units per liter (IU/L) | Standard Deviation 4.42 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Baseline (Day 1) | 26.5 International units per liter (IU/L) | Standard Deviation 11.45 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 38 | 0.2 International units per liter (IU/L) | Standard Deviation 14.33 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 10 | -1.7 International units per liter (IU/L) | Standard Deviation 6.53 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 2 | -1.2 International units per liter (IU/L) | Standard Deviation 4.96 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 31 | 0.3 International units per liter (IU/L) | Standard Deviation 12.6 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 4 | -3.2 International units per liter (IU/L) | Standard Deviation 9.02 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 7 | -4.0 International units per liter (IU/L) | Standard Deviation 3.63 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 7 | -4.8 International units per liter (IU/L) | Standard Deviation 6.97 |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 7 | -3.5 International units per liter (IU/L) | Standard Deviation 5.36 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 17 | 0.9 International units per liter (IU/L) | Standard Deviation 6.72 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Baseline (Day 1) | 30.4 International units per liter (IU/L) | Standard Deviation 20.82 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 2 | 4.3 International units per liter (IU/L) | Standard Deviation 11.7 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 4 | 0.0 International units per liter (IU/L) | Standard Deviation 12.41 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 7 | -6.4 International units per liter (IU/L) | Standard Deviation 14.39 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 10 | -6.1 International units per liter (IU/L) | Standard Deviation 16.95 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 17 | -8.0 International units per liter (IU/L) | Standard Deviation 13.99 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 24 | -8.6 International units per liter (IU/L) | Standard Deviation 14.41 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 31 | -10.4 International units per liter (IU/L) | Standard Deviation 11.84 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 38 | -13.0 International units per liter (IU/L) | Standard Deviation 16.67 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Baseline (Day 1) | 25.9 International units per liter (IU/L) | Standard Deviation 8.76 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 2 | 2.6 International units per liter (IU/L) | Standard Deviation 10.06 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 4 | -2.9 International units per liter (IU/L) | Standard Deviation 6.12 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 7 | -4.9 International units per liter (IU/L) | Standard Deviation 6.57 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 10 | -4.7 International units per liter (IU/L) | Standard Deviation 7.45 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 17 | -5.1 International units per liter (IU/L) | Standard Deviation 7.36 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 24 | -3.3 International units per liter (IU/L) | Standard Deviation 6.73 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 31 | -2.4 International units per liter (IU/L) | Standard Deviation 6.45 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 38 | -6.0 International units per liter (IU/L) | Standard Deviation 9.36 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Baseline (Day 1) | 72.9 International units per liter (IU/L) | Standard Deviation 10.06 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 2 | 0.6 International units per liter (IU/L) | Standard Deviation 3.26 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 4 | 2.9 International units per liter (IU/L) | Standard Deviation 5.84 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 7 | -2.6 International units per liter (IU/L) | Standard Deviation 4.72 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 10 | 2.1 International units per liter (IU/L) | Standard Deviation 3.89 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 24 | -0.7 International units per liter (IU/L) | Standard Deviation 6.8 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 31 | 0.1 International units per liter (IU/L) | Standard Deviation 9.01 |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 38 | -0.6 International units per liter (IU/L) | Standard Deviation 5.83 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 10 | 2.0 International units per liter (IU/L) | Standard Deviation 11.79 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 38 | -3.0 International units per liter (IU/L) | Standard Deviation 21.17 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 4 | 13.3 International units per liter (IU/L) | Standard Deviation 18.01 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 7 | -0.7 International units per liter (IU/L) | Standard Deviation 4.73 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 4 | 1.3 International units per liter (IU/L) | Standard Deviation 3.06 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 31 | 20.3 International units per liter (IU/L) | Standard Deviation 14.36 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 7 | 2.7 International units per liter (IU/L) | Standard Deviation 15.82 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 2 | 0.0 International units per liter (IU/L) | Standard Deviation 3.46 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Baseline (Day 1) | 22.3 International units per liter (IU/L) | Standard Deviation 11.68 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 2 | 0.0 International units per liter (IU/L) | Standard Deviation 4 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 10 | 5.7 International units per liter (IU/L) | Standard Deviation 13.65 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 38 | -3.0 International units per liter (IU/L) | Standard Deviation 5.57 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 31 | -5.0 International units per liter (IU/L) | Standard Deviation 4.58 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 24 | -4.3 International units per liter (IU/L) | Standard Deviation 4.51 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 17 | 8.3 International units per liter (IU/L) | Standard Deviation 4.93 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 17 | -3.0 International units per liter (IU/L) | Standard Deviation 8.72 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 10 | 8.3 International units per liter (IU/L) | Standard Deviation 16.5 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Baseline (Day 1) | 21.0 International units per liter (IU/L) | Standard Deviation 7.21 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 24 | -1.3 International units per liter (IU/L) | Standard Deviation 17.01 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 38 | 0.3 International units per liter (IU/L) | Standard Deviation 8.02 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 7 | -1.3 International units per liter (IU/L) | Standard Deviation 5.86 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Baseline (Day 1) | 103.7 International units per liter (IU/L) | Standard Deviation 56 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 31 | -3.0 International units per liter (IU/L) | Standard Deviation 5.2 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 24 | -4.0 International units per liter (IU/L) | Standard Deviation 7 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALT, Day 4 | -1.0 International units per liter (IU/L) | Standard Deviation 1 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | ALP, Day 2 | 7.3 International units per liter (IU/L) | Standard Deviation 13.58 |
| Placebo | Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) | AST, Day 17 | -1.3 International units per liter (IU/L) | Standard Deviation 8.74 |
Secondary
Monotherapy and Follow-up: Number of Participants With AEs by Severity
The severity was assessed using The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.1 where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening and Grade 5 = Death.
Time frame: Day 1 to Day 38
Population: Analysis was performed on Safety Set. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified duration. Each participant is counted once across both the periods, reflecting the total number of participants affected by any adverse event.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 4 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 2 | 1 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 5 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 3 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 1 | 3 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 3 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 4 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 5 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 2 | 2 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 1 | 4 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 3 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 1 | 3 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 2 | 2 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 4 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 5 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 4 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 2 | 1 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 1 | 1 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 3 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With AEs by Severity | Grade 5 | 0 Participants |
Secondary
Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Any AEs = occurrence of the symptom regardless of intensity grade.
Time frame: Day 1 to Day 38
Population: Analysis was performed on the Safety Set, which included all randomized participants who received at least one partial or full dose of the study intervention. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified duration. Each participant is counted once across both the periods, reflecting the total number of participants affected by any adverse event.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE) | 4 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE) | 6 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE) | 5 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE) | 2 Participants |
Secondary
Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin
Liver panel parameters assessed were: ALT, AST, ALP, bilirubin. The parameters were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase is defined as an increase in grade relative to baseline grade.
Time frame: From Baseline (Day 1) and up to Day 38
Population: Analysis was performed on Safety Set. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified duration.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 2 | 1 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 1 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 1 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 1 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 1 | 1 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 1 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 1 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 1 | 1 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 1 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 1 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 1 | 1 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 1 | 1 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 3 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 4 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 1 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 2 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 2 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 2 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 2 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 1 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 2 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 3 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 4 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 4 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 1 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 4 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 3 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | AST, Increase to Grade 1 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALT, Increase to Grade 3 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 3 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 4 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | ALP, Increase to Grade 2 | 0 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin | Bilirubin, Increase to Grade 1 | 0 Participants |
Secondary
Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein
Participants are categorized based on changes in their liver panel laboratory parameters (protein) to 'Low,' 'Normal,' or 'High,' unless there is no change in their initial category. Participants whose lab values remain unchanged (e.g., 'High' to 'High') or whose values return to normal are recorded in the 'To Normal or No Change' category. Participants may be counted in both the 'To Low' and 'To High' categories if their values fluctuate between these states. As a result, the percentages may exceed 100% due to dual categorization. Participants with a missing baseline value are assumed to have a normal baseline value.
Time frame: From Baseline (Day 1) and up to Day 38
Population: Analysis was performed on Safety Set. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified duration.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To High | 2 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To Normal or No Change | 4 Participants |
| VH4524184 Dose 1 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To Low | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To High | 2 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To Low | 0 Participants |
| VH4524184 Dose 2 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To Normal or No Change | 4 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To Normal or No Change | 5 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To Low | 0 Participants |
| VH4524184 Dose 3 | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To High | 2 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To High | 1 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To Normal or No Change | 2 Participants |
| Placebo | Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein | To Low | 0 Participants |
Secondary
Monotherapy: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10
Blood samples were collected for assessment of T-cells subsets (CD4+ T-cells count) by flow cytometry at Day 10 compared to Baseline.
Time frame: At Day 10 compared to Baseline (Day 1)
Population: Analysis was performed on Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10 | 131.333 CD4+ million cells per Liter (10^6/L) | Standard Deviation 98.4473 |
| VH4524184 Dose 2 | Monotherapy: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10 | 68.667 CD4+ million cells per Liter (10^6/L) | Standard Deviation 122.1191 |
| VH4524184 Dose 3 | Monotherapy: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10 | 47.000 CD4+ million cells per Liter (10^6/L) | Standard Deviation 45.9093 |
| Placebo | Monotherapy: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10 | 63.667 CD4+ million cells per Liter (10^6/L) | Standard Deviation 216.1512 |
Secondary
Monotherapy: Correlation of VH4524184 Cmax With Maximum Plasma HIV-1 RNA Log 10 Change From Baseline Through Day 10
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value. Change from baseline is defined as post-dose visit value minus baseline value. Statistical analysis for relationship between PK parameter (Cmax) and PD measure (change from baseline in logarithm to base 10 (log10) values for maximum plasma HIV-1 RNA) were explored using an Emax non-linear mixed-effects model. The model parameters estimated were maximum response (Emax) which is defined as the maximum change (at infinite exposure) and EC50 which defines the PK parameter value that attains 50 percent (%) of the maximal effect
Time frame: From Day 1 to Day 10
Population: Analysis was performed on PK Set. Only participants with data available at the specified duration were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Correlation of VH4524184 Cmax With Maximum Plasma HIV-1 RNA Log 10 Change From Baseline Through Day 10 | -1.17 Log10 copies/mL | Standard Deviation 0.46 |
| VH4524184 Dose 2 | Monotherapy: Correlation of VH4524184 Cmax With Maximum Plasma HIV-1 RNA Log 10 Change From Baseline Through Day 10 | -2.15 Log10 copies/mL | Standard Deviation 0.254 |
| VH4524184 Dose 3 | Monotherapy: Correlation of VH4524184 Cmax With Maximum Plasma HIV-1 RNA Log 10 Change From Baseline Through Day 10 | -2.31 Log10 copies/mL | Standard Deviation 0.463 |
Secondary
Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184
Blood samples were collected at indicated time points for Pharmacokinetic (PK) analysis of VH4524184.
Time frame: At Day 1 and Day 7
Population: Analysis was performed on PK Set, which included All participants in the Safety analysis set who had at least 1 non-missing PK assessment. Only participants with data available at the specified timepoints were included in this analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184 | Day 1 | 1332.57 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 16.78 |
| VH4524184 Dose 1 | Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184 | Day 7 | 1488.59 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32.06 |
| VH4524184 Dose 2 | Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184 | Day 1 | 6173.61 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 30.71 |
| VH4524184 Dose 2 | Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184 | Day 7 | 7112.60 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 16.59 |
| VH4524184 Dose 3 | Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184 | Day 1 | 23589.70 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32.39 |
| VH4524184 Dose 3 | Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184 | Day 7 | 23069.92 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45.77 |
Secondary
Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation
Time frame: Day 1 to Day 7
Population: Analysis was performed on Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation | 0 Participants |
| VH4524184 Dose 2 | Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation | 0 Participants |
| VH4524184 Dose 3 | Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation | 0 Participants |
| Placebo | Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation | 0 Participants |
Secondary
Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance
Plasma samples were collected to assess treatment emergent Genotypic Resistance.
Time frame: At Baseline (Day 1) and Day 10
Population: Analysis was performed on FAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance | Day 1 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance | Day 10 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance | Day 1 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance | Day 10 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance | Day 1 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance | Day 10 | 0 Participants |
Secondary
Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance
Plasma samples were collected to assess treatment emergent Phenotypic Resistance.
Time frame: At Baseline (Day 1) and Day 10
Population: Analysis was performed on FAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance | Day 1 | 0 Participants |
| VH4524184 Dose 1 | Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance | Day 10 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance | Day 1 | 0 Participants |
| VH4524184 Dose 2 | Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance | Day 10 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance | Day 1 | 0 Participants |
| VH4524184 Dose 3 | Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance | Day 10 | 0 Participants |
Secondary
Monotherapy: Plasma Concentration of VH4524184 at Day 10
Blood samples was collected at indicated time point for PK analysis of VH4524184.
Time frame: At Day 10
Population: Analysis was performed on PK Set. Only participants with data available at the specified timepoint were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Plasma Concentration of VH4524184 at Day 10 | 127.5 ng/mL | Standard Deviation 75.59 |
| VH4524184 Dose 2 | Monotherapy: Plasma Concentration of VH4524184 at Day 10 | 523.5 ng/mL | Standard Deviation 324.5 |
| VH4524184 Dose 3 | Monotherapy: Plasma Concentration of VH4524184 at Day 10 | 1328.3 ng/mL | Standard Deviation 486.99 |
Secondary
Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184
Blood samples were collected at indicated time points for PK analysis of VH4524184.
Time frame: At Day 1 and Day 7
Population: Analysis was performed on PK Set. Only participants with data available at the specified timepoints were included in this analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VH4524184 Dose 1 | Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184 | Day 1 | 3.13 hours |
| VH4524184 Dose 1 | Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184 | Day 7 | 4.00 hours |
| VH4524184 Dose 2 | Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184 | Day 1 | 4.00 hours |
| VH4524184 Dose 2 | Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184 | Day 7 | 4.49 hours |
| VH4524184 Dose 3 | Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184 | Day 1 | 2.00 hours |
| VH4524184 Dose 3 | Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184 | Day 7 | 2.13 hours |