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
372
VH4524184 to be taken orally.
VH4524184 LAI Formulation A administered subcutaneously.
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 Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
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 pruritus. 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 Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Percentage of participants discontinuing the treatment due to AEs
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
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 Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
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 Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
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rHuPH20 administered subcutaneously.
VH4524184 LAI Formulation B administered subcutaneously.
Placebo Formulation B administered subcutaneously.
VH4524184 LAI Formulation A administered intramuscularly.
Placebo Formulation A administered intramuscularly.
VH4524184 LAI Formulation B administered intramuscularly.
Placebo Formulation B administered intramuscularly.
Change from baseline in international normalized ratio (INR) parameters
The liver panel laboratory parameters are assessed after the administration of LAI VH4524184.
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Maximum toxicity grade increase from baseline in ALT, AST and alkaline phosphatase
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Maximum toxicity grade increase from baseline in total bilirubin
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Maximum toxicity grade increase from baseline in INR
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Percentage of participants reporting injection site reaction (ISR) AEs
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 Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Duration of injection site reaction AEs
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
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 Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
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 Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Maximum observed plasma drug concentration (Cmax) of LAI VH4524184 following single dose administration
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Cmax of LAI VH4524184 following multiple dose administration
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
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 Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Tmax of LAI VH4524184 following multiple dose administration
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
Apparent terminal half-life (t1/2) of LAI VH4524184 following single dose administration
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
t1/2 of LAI VH4524184 following multiple dose administration
Time frame: From first dose administration (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants
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 (Day 1) up to Week 52 post last dose, and Week 80 post last dose for a sub-group of participants