Phase 1
N=73
First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants
HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT05163522 ↗Enrolled (actual)
73
Serious AEs
0.0%
Results posted
Jul 2025
Primary outcome: Primary: Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity — 4; 2; 3; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- VH4004280 (Drug); Placebo (Drug); Midazolam (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- ViiV Healthcare
- Primary completion
- Jun 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity |
4; 2; 3; 0; 0; 1 | — |
| PRIMARY Part 2: Number of Participants With Any AEs and by Severity |
3; 4; 7; 4; 3; 4 | — |
| PRIMARY Part 3: Number of Participants With Any AEs and by Severity |
3; 2; 0; 1; 0; 0 | — |
| PRIMARY Part 2: Number of Participants Discontinuing Treatment Due to AEs |
0; 0; 0; 0 | — |
| PRIMARY Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin |
2.5650; 1.9950; 2.9314; 2.2800; 2.2800; 2.8500 | — |
| PRIMARY Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) |
51.8; 64.7; 67.1; 69.0; 64.0; 61.8 | — |
| PRIMARY Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin |
2.2800; 2.8500; 2.1375; 1.7100; 2.1803; 3.1065 | — |
| PRIMARY Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST |
66.2; 53.7; 57.5; 56.7; 69.0; 52.0 | — |
| PRIMARY Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin |
1.9950; 2.3085; 2.2515; 2.1660; 1.9380; 2.2800 | — |
| PRIMARY Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST |
55.7; 47.8; 50.2; 50.8; 48.8; 49.7 | — |
| PRIMARY Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin |
2.5650; 1.9950; 2.9314; 2.2800; 2.2800; 2.8500 | — |
| PRIMARY Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST |
51.8; 64.7; 67.1; 69.0; 64.0; 61.8 | — |
| PRIMARY Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin |
2.2800; 2.8500; 2.1375; 1.7100; 0.0428; 0.2565 | — |
| PRIMARY Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST |
66.2; 53.7; 57.5; 56.7; 4.0; -1.7 | — |
| PRIMARY Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin |
1.9950; 0.3135; 0.2565; 0.1710; -0.0570; 0.2850 | — |
| PRIMARY Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST |
55.7; -7.8; -5.5; -4.8; -6.8; -6.0 | — |
| PRIMARY Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters |
1; 1; 0; 1; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters |
1; 1; 0; 1; 0; 0 | — |
| PRIMARY Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280 |
1396.25; 16829.76; 51168.22; 174441.72; 215339.87 | — |
| PRIMARY Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (AUC[0-t]) Following Repeat Dose Administration of VH4004280 |
6268.14; 14869.75; 15157.94; 449239.54; 1882862.73; 1527149.1 | — |
| PRIMARY Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280 |
13.49; 149.77; 438.80; 1342.72; 1630.95 | — |
| PRIMARY Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280 |
9.63; 9.90; 11.15; 10.31; 8.53 | — |
| PRIMARY Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280 |
145.82; 149.91; 149.94; 177.58; 172.66 | — |
| PRIMARY Part 2: Cmax Following Repeat Dose Administration of VH4004280 |
422.68; 957.92; 972.51; 1725.63; 7573.63; 4487.14 | — |
| PRIMARY Part 2: T1/2 Following Repeat Dose Administration of VH4004280 |
166.29; 147.93; 207.76 | — |
| PRIMARY Part 2: Tmax Following Repeat Dose Administration of VH4004280 |
9.28; 9.57; 9.68; 9.58; 15.49; 9.33 | — |
Summary
This FTIH study aims to evaluate the safety, tolerability and PK of the novel investigational Human immunodeficiency virus (HIV)-1 capsid inhibitor VH4004280 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD), Part 2 will investigate multiple ascending doses and drug-drug interaction (MAD/MAD DDI) Part 3 will investigate single dose relative bioavailability (RBA) of a new formulation of VH4004280.
Eligibility Criteria
Inclusion criteria
- Participant must be 18 to 55 years of age inclusive.
- Participants who are overtly healthy.
- Male or female participants of non-childbearing potential.
- Capable of giving signed informed consent.
Exclusion criteria
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug or interfering with the interpretation of data.
- Abnormal blood pressure.
- Symptomatic herpes zoster.
- Evidence of active or latent tuberculosis (TB).
- Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- Breast cancer within the past 10 years.
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QT interval corrected for heart rate according to Fridericia's formula (QTcF) greater than (>)450 milliseconds (msec).
- Past or intended use of over-the-counter or prescription medication including herbal medications.
- Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
- Exposure to more than 4 new investigational products within 12 months prior to the first dosing day.
- Current enrollment or past participation in another investigational study.
- ALT >1.5 times upper limit of normal (ULN), total bilirubin >1.5 times ULN, and/or estimated serum creatinine clearance less than 60 milliliters per minute.
- History of or current infection with hepatitis B or hepatitis C.
- Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test, having signs and symptoms, or having contact with known Coronavirus Disease-2019 (COVID-19) positive person/s.
- Positive HIV antibody test.
- User of tobacco or nicotine-containing products, regular alcohol consumption and/or regular use of known drugs of abuse.
- Sensitivity to the study drug, or components thereof.
Data sourced from ClinicalTrials.gov (NCT05163522). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.