The purpose of this study is to investigate safety, pharmacokinetics and tolerability following single ascending dose (SAD) and multiple ascending doses (MAD) of VH4011499 administered subcutaneously (SC) and intramuscularly (IM) in participants without HIV.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
168
VH4011499 low dose Injection will be administered subcutaneously and/or intramuscularly.
VH4011499 high dose Injection will be administered subcutaneously and/or intramuscularly.
Placebo Injection will be administered either subcutaneously or intramuscularly.
GSK Investigational Site
Las Vegas, Nevada, United States
RECRUITINGGSK Investigational Site
Austin, Texas, United States
RECRUITINGNumber of participants with adverse events (AEs), including Injection Site Reaction (ISR) AEs, as per severity of Grade 2-5 using the DAIDS grading scale
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. Severity of AEs and ISR AEs including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis, will be assessed using Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life threatening and Grade 5=Death.
Time frame: Up to Week 78
Area under the plasma-concentration time curve from time zero to infinity (AUC0-inf) of VH4011499 for SAD group
Time frame: Up to Week 78
Area under the plasma concentration vs time curve (AUC0-tau) for MAD group
Time frame: Up to Week 78
Maximum observed plasma concentration (Cmax) of VH4011499
Time frame: Up to Week 78
Time to maximum observed plasma concentration (tmax) of VH4011499
Time frame: Up to Week 78
Apparent terminal half-life (t1/2) of VH4011499
Time frame: Up to Week 78
Absolute values of liver chemistry parameters: total bilirubin and direct bilirubin (micromoles per liter [umol/L]) for SAD group
Time frame: At Day 4, Day 10, Week 4, Week 24 and Week 48
Absolute values of liver chemistry parameters: total bilirubin and direct bilirubin (micromoles per liter [umol/L]) for MAD group
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Time frame: At Day 4, Day 10, Day 29, Day 32, Day 38, Week 24 and Week 52
Change from baseline in liver chemistry parameters: total bilirubin and direct bilirubin (umol/L) for SAD group
Time frame: At Day 4, Day 10, Week 4, Week 24 and Week 48 compared to Baseline (Prior to Day 1)
Change from baseline in liver chemistry parameters: total bilirubin and direct bilirubin (umol/L) for MAD group
Time frame: At Day 4, Day 10, Day 29, Day 32, Day 38, Week 24 and Week 52 compared to Baseline (Prior to Day 1)
Number of participants with maximum toxicity grade change from baseline in liver chemistry parameters: total bilirubin, direct bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)
Time frame: Baseline (Prior to Day 1) and Up to Week 78
Absolute values of liver chemistry parameters: ALP, AST, and ALT (International Units per Liter [IU/L]) for SAD group
Time frame: At Day 4, Day 10, Week 4, Week 24 and Week 48
Absolute values of liver chemistry parameters: ALP, AST, and ALT (International Units per Liter [IU/L]) for MAD group
Time frame: At Day 4, Day 10, Day 29, Day 32, Day 38, Week 24 and Week 52
Change from Baseline in Liver Chemistry Parameters: ALP, AST, and ALT (IU/L) for SAD group
Time frame: At Day 4, Day 10, Week 4, Week 24 and Week 48 compared to Baseline (Prior to Day 1)
Change from Baseline in Liver Chemistry Parameters: ALP, AST, and ALT (IU/L) for MAD group
Time frame: At Day 4, Day 10, Day 29, Day 32, Day 38, Week 24 and Week 52 compared to Baseline (Prior to Day 1)
Number of participants with Grade 1 AEs (including ISR AEs) as per severity using the DAIDS grading scale
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. Severity of AEs and ISR AEs including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis, will be assessed using Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life threatening and Grade 5=Death.
Time frame: Week 78 post dose (Week 82 for MAD Group)
Duration of ISR (Days) AEs by grade using the DAIDS grading scale
Time frame: Week 78 post dose (Week 82 for MAD Group)