Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT06039579 | Proof of Concept Treatment Study of Orally Administered VH4004280 or VH4011499 in HIV-1 Infected Adults | PHASE2 | COMPLETED | 44 | — | — | Oct 25, 2023 | Jun 24, 2024 | Sep 30, 2025 | 20 | United States, Argentina +7 |
| NCT06012136 | A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Suspension Injection of Investigational Capsid Inhibitors Compared to Placebo in Healthy Adults | PHASE1 | ACTIVE NOT_RECRUITING | 85 | — | — | Aug 24, 2023 | Jun 9, 2026 | Sep 5, 2025 | 2 | United States |
| NCT05163522 | First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants | PHASE1 | COMPLETED | 73 | — | — | Dec 13, 2021 | Jun 21, 2023 | Jul 30, 2025 | 1 | United States |
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum change from baseline was calculated by subtracting the baseline value from the post-dose visit value when the plasma HIV-1 RNA reached its minimum level up to Day 11 (inclusive). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. The results were expressed as log10 copies per milliliter (log10 c/mL).
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum change from baseline was calculated by subtracting the baseline value from the post-dose visit value when the plasma HIV-1 RNA reached its minimum level up to Day 11 (inclusive). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
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. Severity of Adverse Event will be assessed using Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
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. Severity of Adverse Event will be assessed using Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent.
Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent.
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
The DAIDS Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
The DAIDS Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Number of participants who discontinued treatment due to AEs are presented.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Standard Deviation (SD)=0.00000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.00000.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented.
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented.
Blood samples were collected as assessed by protocol, at specific time points for pharmacokinetic (PK) analysis to determine AUC(0-inf). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. Geometric Coefficient of Variation was expressed in percentages.
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine AUC(0-t). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations.
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
| Arm | Type | Description |
|---|---|---|
| Part 1a: VH4004280 Dose Level 1 | EXPERIMENTAL | Participants received a single dose of VH4004280 Dose Level 1 (low concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label antiretroviral therapy (ART) up to day 39. |
| Part 1a: VH4004280 Dose Level 2 | EXPERIMENTAL | Participants received a single dose of VH4004280 Dose Level 2 (medium concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39. |
| Part 2a: VH4004280 pre-specified dose | EXPERIMENTAL | Participants received a single pre-specified dose of VH4004280 (high concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39. |
| Matching placebo for VH4004280 | PLACEBO_COMPARATOR | Participants received a matching placebo for VH4004280 on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39. |
| Part 1b: VH4011499 Dose Level 1 | EXPERIMENTAL | Participants received a single dose of VH4011499 Dose Level 1 (low concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants had the option to switch to an open-label ART up to day 39. |
| Part 1b: VH4011499 Dose Level 2 | EXPERIMENTAL | Participants received a single dose of VH4011499 Dose Level 2 (medium concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39. |
| Part 2b: VH4011499 pre-specified dose | EXPERIMENTAL | Participants received a single pre-specified dose of VH4011499 (high concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39. |
| Matching placebo for VH4011499 | PLACEBO_COMPARATOR | Participants received a matching placebo for VH4011499 on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39. |
| Part 1 Single Ascending Dose (SAD): Participants Receiving VH4004280 | EXPERIMENTAL | VH4004280 injections are administered subcutaneously (SC), SC+ rHuPH20, or intramuscularly (IM). |
| Part 1: Participants Receiving Placebo | PLACEBO_COMPARATOR | Placebo injection is administered. |
| Part 2 SAD: Participants Receiving VH4011499 | EXPERIMENTAL | VH4011499 injections are administered SC, SC+ rHuPH20, or IM. |
| Part 2 Multiple Ascending Dose (MAD): Participants Receiving VH4011499 | EXPERIMENTAL | VH4011499 injections are administered IM. |
| Part 2: Participants Receiving Placebo | PLACEBO_COMPARATOR | Placebo injection is administered. |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | PLACEBO_COMPARATOR | Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49. |
| Part 1 (SAD): VH4004280 10 mg PiB | EXPERIMENTAL | Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. |
| Part 1 (SAD): VH4004280 50 mg PiB | EXPERIMENTAL | Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. |
| Part 1 (SAD): VH4004280 150 mg PiB | EXPERIMENTAL | Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. |
| Part 1 (SAD): VH4004280 450 mg PiB | EXPERIMENTAL | Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. |
| Part 1 (SAD): VH4004280 900 mg PiB | EXPERIMENTAL | Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. |
| Part 2 Multiple Ascending Dose (MAD): Placebo PiB | PLACEBO_COMPARATOR | Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63. |
| Part 2 (MAD): VH4004280 100 mg PiB | EXPERIMENTAL | Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63. |
| Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB | EXPERIMENTAL | Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63. |
| Part 2 (MAD): VH4004280 350 mg PiB | EXPERIMENTAL | Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63. |
| Part 3 (Single dose): VH4004280 450 mg tablet | EXPERIMENTAL | Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49. |
| Name | Type | Description |
|---|---|---|
| VH4004280 | DRUG | VH4004280 was administered as tablets orally at Day 1. |
| VH4011499 | DRUG | VH4011499 was administered as tablets orally at Day 1 and Day 6. |
| VH4004280 Matching Placebo | DRUG | VH4004280 Matching Placebo was administered as tablets orally at Day 1. |
| VH4011499 Matching Placebo | DRUG | VH4011499 Matching Placebo was administered as tablets orally at Day 1 and Day 6. |
| Antiretroviral therapy | DRUG | Antiretroviral therapy was administered as available and as per investigator's recommendation. |
| Placebo | DRUG | Placebo will be administered. |
| Midazolam | DRUG | Midazolam will be administered |
Inclusion Criteria: * Participants who are overtly healthy (other than HIV-1 infection). * Screening cluster of differentiation-4 (CD4+) T-cell count greater than or equal to (≥)200 cells/microliter (µL). * Documented HIV-1 infection and Screening plasma HIV-1 RNA ≥3000 copies/milliliter (mL). * Tr...