Clinical trial NCT05163522: First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants
Official title: A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4004280 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: First-time-in-human
GSK4004280
VH4004280
HIV-1 capsid inhibitor
Single ascending doses
Multiple ascending doses
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2021-12-20
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Part 1: Number of participants with adverse events (AEs)
timeFrame: Up to Day 49
measure: Part 2: Number of participants with AEs
timeFrame: Up to Day 63
measure: Part 3: Number of participants with AEs
timeFrame: Up to Day 49
measure: Part 1: Number of participants with AEs by severity
timeFrame: Up to Day 49
measure: Part 2: Number of participants with AEs by severity
timeFrame: Up to Day 63
measure: Part 3: Number of participants with AEs by severity
timeFrame: Up to Day 49
measure: Part 2: Percentage of participants discontinuing treatment due to AEs
timeFrame: Up to Day 14
measure: Part 1: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)
timeFrame: Up to Day 49
measure: Part 1: Absolute values of liver panel parameters: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and Aspartate aminotransferase (AST) (International units per Liter)
timeFrame: Up to Day 49
measure: Part 2: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)
timeFrame: Up to Day 63
measure: Part 2: Absolute values of liver panel parameters: ALT, ALP and AST (International units per Liter)
timeFrame: Up to Day 63
measure: Part 3: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)
timeFrame: Up to Day 49
measure: Part 3: Absolute values of liver panel parameters: ALT, ALP and AST (International units per Liter)
timeFrame: Up to Day 49
measure: Part 1: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)
timeFrame: Baseline and up to Day 49
measure: Part 1: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)
timeFrame: Baseline and up to Day 49
measure: Part 2: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)
timeFrame: Baseline and up to Day 63
measure: Part 2: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)
timeFrame: Baseline and up to Day 63
measure: Part 3: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)
timeFrame: Baseline and up to Day 49
measure: Part 3: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)
timeFrame: Baseline and up to Day 49
measure: Part 1: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters
timeFrame: Up to Day 49
measure: Part 2: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters
timeFrame: Up to Day 63
measure: Part 3: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters
timeFrame: Up to Day 49
measure: Part 1: Area under the plasma concentration time curve from time zero to infinity (AUC[0-infinity]) following single dose administration of VH4004280
timeFrame: Up to Day 49
measure: Part 2: Area under the plasma concentration time curve over a dosing interval from time of dosing to the time of the subsequent dose (AUC[0-tau]) following repeat dose administration of VH4004280
timeFrame: Up to Day 63
measure: Part 1: Maximum observed plasma concentration (Cmax) following single dose administration of VH4004280
timeFrame: Up to Day 49
measure: Part 1: Time to maximum observed plasma concentration (Tmax) and Apparent terminal half-life (T1/2) following single dose administration of VH4004280 (Hours)
timeFrame: Up to Day 49
measure: Part 2: Cmax following repeat dose administration of VH4004280
timeFrame: Up to Day 63
measure: Part 2: Tmax and T1/2 following repeat dose administration of VH4004280 (Hours)
timeFrame: Up to Day 63
Secondary outcomes:
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: