This study is to evaluate antiviral activity, efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK3810109A in HIV-1 infected treatment naive adults. Participants will receive a single dose of GSK3810109A administered either intravenously (IV) or subcutaneously (SC). The study includes a screening phase, a randomized monotherapy phase and a standard of care follow-up phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
62
GSK3810109A available as sterile aqueous solution.
Dolutegravir+lamivudine regimen administered in consistence with investigator input and local guidelines
GSK Investigational Site
Long Beach, California, United States
Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum decline from baseline in plasma HIV-1 RNA were measured in participants. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase
Number of Participants With Adverse Events (AEs) - Monotherapy Phase
An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: Up to Day 84 or end of Monotherapy Phase
Number of Participants With Worst-case Maximum Grade 2-4 Increase in Post-baseline Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Compared to the Baseline Values - Monotherapy Phase
Blood samples were collected for the analysis of ALT and AST parameters. The parameters ALT and AST were graded using the Division of Acquired Immunodeficiency Syndrome (DAIDS) criteria Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data of number of participants with 2-4 grade increase at worst-case post-baseline (maximum grade increase post-baseline) is presented. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
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GSK Investigational Site
Los Angeles, California, United States
GSK Investigational Site
Los Angeles, California, United States
GSK Investigational Site
Orlando, Florida, United States
GSK Investigational Site
Berkley, Michigan, United States
GSK Investigational Site
Manhasset, New York, United States
GSK Investigational Site
Dallas, Texas, United States
GSK Investigational Site
Buenos Aires, Argentina
GSK Investigational Site
Buenos Aires, Argentina
GSK Investigational Site
Buenos Aires, Argentina
...and 14 more locations
Time frame: Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase
Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase
A 12-lead ECG were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. ECG findings were categorized as normal, abnormal clinically significant (CS) and abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal (CS and NCS) ECG findings are presented. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: Up to Day 84 or end of Monotherapy Phase
Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase
Number of participants with grade 2-4 injection site reactions are presented. The ISR were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria Version 2.1 where grades were defined based on numeric criteria as follows Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: Up to Day 84 or end of Monotherapy Phase
Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3810109A.
Time frame: Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14
Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase
Cmax is defined as maximum observed concentration of GSK3810109A.
Time frame: Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14
Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase
Tmax is defined as time to reach Cmax
Time frame: Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14
Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase
Blood samples were collected at indicated time point for pharmacokinetic analysis of GSK3810109A.
Time frame: At Day 14
Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. Statistical analysis for relationship between PK parameter (Cmax) and PD measure (change from baseline in logarithm to base 10 (log10) values for plasma HIV-1 RNA) were explored using an Emax non-linear model. The model parameters estimated included: maximum response (Emax), PK parameter value that attains 50 percent (%) of the maximal effect (EC50) and residual variability (s2e). End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase
Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase
Blood samples were collected as prespecified. CD4+ and CD8+ T cell counts were assessed using flow cytometry. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: From Day 1 (Baseline) and up to Day 84 or end of Monotherapy Phase
Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase
Blood samples were collected as prespecified. CD4+ and CD8+ T cell counts were assessed using flow cytometry.
Time frame: Up to Week 48 (SOC Phase)
Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase
Blood samples were collected as prespecified. CD4+ and CD8+ T cell counts were assessed using flow cytometry. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: Up to Day 84 or end of Monotherapy Phase (compared with baseline [Day 1])
Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase
Blood samples were collected as prespecified. CD4+ and CD8+ T cell counts were assessed using flow cytometry.
Time frame: Up to Week 48 (SOC Phase)
Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase
Serum samples were collected to analyze the presence of ADAs against GSK3810109A using validated immunoassays. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: At Day 1 and Day 84 or end of Monotherapy Phase
Number of Participants With Positive ADAs Against GSK3810109A - SOC Phase
Serum samples were collected to analyze the presence of ADAs against GSK3810109A using validated immunoassays.
Time frame: At Week 48 (SOC Phase)
Titers of Positive ADAs Against GSK3810109A - Monotherapy Phase
Serum samples were collected to analyze the presence of ADAs against GSK3810109A using validated immunoassays. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.
Time frame: At Day 84 or end of Monotherapy Phase
Titers of Positive ADAs Against GSK3810109A - SOC Phase
Serum samples were collected to analyze the presence of ADAs against GSK3810109A using validated immunoassays.
Time frame: At Week 48 (SOC Phase)