Clinical trial NCT05393271: First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4011499 in Healthy Participants
Official title: A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4011499 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: GSK4011499
VH4011499
First-time-in-human
HIV-1 capsid inhibitor
Single ascending doses
Multiple ascending doses
Drug-drug Interaction
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2022-05-26
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a randomized and placebo-controlled study.
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 VH4011499 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD) and Part 2 will investigate multiple ascending doses (MAD). Part 3 will investigate single dose of a new formulation of VH4011499. The transition from SAD to MAD will be based on the assessment of the Safety and Dose Escalation Committee.


Eligibility criteria: Inclusion Criteria:

* Participants who are overtly healthy.
* Participants must have two consecutive Severe Acute Respiratory Syndrome Coronavirus 2 (SARs-CoV-2) Polymerase chain reaction (PCR) negative results prior to dosing.
* Participants must have body weight \> 50 kilograms (kg) and body mass index (BMI) within the range 19-32 kilograms per meter square (kg/m\^2).
* Male or female participants (either of non-childbearing potential or of child-bearing potential and using acceptable contraception).
* 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.
* 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 within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study, unless in the opinion of the Investigator and Sponsor, the medication will not interfere with the study medications, procedures, or compromise participant safety.
* Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
* Exposure to more than 4 investigational products within 12 months prior to dosing.
* Current enrollment or recent 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 within 14 days.
* Positive HIV antibody test.
* Use 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 midazolam, excipients contained therein, benzodiazepines, or drug or other allergy that, contraindicates participation in the study.

Primary outcomes:
measure: Part 1: Number of Participants With Adverse Events (AEs)
timeFrame: Up to Day 28
measure: Part 2: Number of Participants With AEs
timeFrame: Up to Day 42
measure: Part 3: Number of Participants With AEs
timeFrame: Up to Day 28
measure: Part 1: Number of Participants With AEs by Severity
timeFrame: Up to Day 28
measure: Part 2: Number of Participants With AEs by Severity
timeFrame: Up to Day 42
measure: Part 3: Number of Participants With AEs by Severity
timeFrame: Up to Day 28
measure: Part 2: Number of Participants Discontinuing Treatment Due to AEs
timeFrame: Up to Day 42
measure: Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
timeFrame: Up to Day 28
measure: Part 1: Absolute Values of Liver Panel Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
timeFrame: Up to Day 28
measure: Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
timeFrame: Up to Day 42
measure: Part 2: Absolute Values of Liver Panel Parameters: ALT, ALP and AST
timeFrame: Up to Day 42
measure: Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
timeFrame: Up to Day 28
measure: Part 3: Absolute Values of Liver Panel Parameters: ALT, ALP and AST
timeFrame: Up to Day 28
measure: Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
timeFrame: From Baseline (Day 1) and up to Day 28
measure: Part 1: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
timeFrame: From Baseline (Day 1) and up to Day 28
measure: Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
timeFrame: From Baseline (Day 1) and up to Day 42
measure: Part 2: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
timeFrame: From Baseline (Day 1) and up to Day 42
measure: Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
timeFrame: From Baseline (Day 1) and up to Day 28
measure: Part 3: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
timeFrame: From Baseline (Day 1) and up to Day 28
measure: Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
timeFrame: Up to Day 28
measure: Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
timeFrame: Up to Day 42
measure: Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
timeFrame: Up to Day 28
measure: Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to Infinity (0-inf) Following Single Dose Administration of VH4011499
timeFrame: At Day 1
measure: Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (0-t) Following Repeat Dose Administration of VH4011499
timeFrame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4011499.
timeFrame: At Day 1
measure: Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4011499
timeFrame: At Day 1
measure: Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4011499
timeFrame: At Day 1
measure: Part 2: Cmax Following Repeat Dose Administration of VH4011499
timeFrame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
measure: Part 2: Tmax Following Repeat Dose Administration of VH4011499
timeFrame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
measure: Part 2: T1/2 Following Repeat Dose Administration of VH4011499
timeFrame: At Day 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Day 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
Secondary outcomes:
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: