The purpose of this study is to identify 1 or more doses of parenterally administered VH4524184 that are safe, well tolerated and yield a PK drug exposure profile necessary to deliver a long-acting antiretroviral therapy for the treatment of HIV-1 infection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
268
VH4524184 to be taken orally.
Low (\<1mL) starting dose of VH4524184 LAI Formulation A administered subcutaneously.
Starting dose of Placebo Formulation A administered subcutaneously.
GSK Investigational Site
Lenexa, Kansas, United States
RECRUITINGGSK Investigational Site
San Antonio, Texas, United States
RECRUITINGGSK Investigational Site
Salt Lake City, Utah, United States
RECRUITINGPercentage of participants reporting adverse events (AEs) and related AEs
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. Related AE = AE assessed by the investigator as related to the study drug.
Time frame: From first study dose administration (Day 1) up to study end (Week 52 post last dose)
Percentage of participants with AEs by severity
Severity of AEs will be assessed using Division of AIDS Table for Grading the Severity of Adult 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.
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Percentage of participants discontinuing the treatment due to AEs
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Change from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase parameters
The liver panel laboratory parameters are assessed after the administration of long-acting injectable (LAI) VH4524184.
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Change from baseline in total bilirubin parameters
The liver panel laboratory parameters are assessed after the administration of LAI VH4524184.
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Change from baseline in international normalized ratio (INR) parameters
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Dose of rHuPH20 administered subcutaneously.
Starting dose of VH4524184 LAI Formulation B administered subcutaneously.
Starting dose of Placebo Formulation B administered subcutaneously.
Starting dose VH4524184 LAI Formulation A administered intramuscularly.
Dose of Placebo Formulation A administered intramuscularly.
Starting dose VH4524184 LAI Formulation B administered intramuscularly.
Dose of Placebo Formulation B administered intramuscularly.
The liver panel laboratory parameters are assessed after the administration of LAI VH4524184.
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Maximum toxicity grade increase from baseline in ALT, AST and alkaline phosphatase
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Maximum toxicity grade increase from baseline in total bilirubin
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Maximum toxicity grade increase from baseline in INR
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Percentage of participants reporting injection site reaction (ISR) AEs
Assessed ISRs are pain, tenderness, infections, erythema, swelling, induration, or nodules (granulomas or cysts). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, and Grade 4 = potentially life threatening.
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Duration of injection site reaction AEs
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinity time (AUC[0-inf]) of LAI VH4524184 following single dose administration
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Area under the plasma drug concentration-time curve from zero (pre-dose) to the end of the dosing interval at steady state (AUC[0-t]) of LAI VH4524184 following multiple dose administration
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Maximum observed plasma drug concentration (Cmax) of LAI VH4524184 following single dose administration
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Cmax of LAI VH4524184 following multiple dose administration
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Time to maximum observed plasma drug concentration (Tmax) of LAI VH4524184 following single dose administration
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Tmax of LAI VH4524184 following multiple dose administration
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Apparent terminal half-life (t1/2) of LAI VH4524184 following single dose administration
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
t1/2 of LAI VH4524184 following multiple dose administration
Time frame: From first dose administration (Day 1) up to study end (Week 52 post last dose)
Percentage of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities
Grade 3 is defined as causing an inability to perform usual social \& functional activities with intervention or hospitalization indicated. Grade 4 is defined as an abnormality that is potentially life-threatening, causing an inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death.
Time frame: From first dose administration of VH4524184 (Day 1) up to study end (Week 52 post last dose)