HIV Infections
Conditions
Keywords
Antiretroviral-naïve, Broadly neutralizing antibody, GSK3810109A, HIV, N6LS
Brief summary
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.
Interventions
BIOLOGICALGSK3810109A
GSK3810109A available as sterile aqueous solution.
BIOLOGICALDolutegravir+lamivudine SOC regimen
Dolutegravir+lamivudine regimen administered in consistence with investigator input and local guidelines
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study
Intervention model description
The is a sequential treatment, two-part study which will include a screening phase, a randomized monotherapy phase and a standard of care follow-up phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent. * Participants must have HIV-1 infection within 45 days of the Screening Visit: Plasma HIV-1 RNA greater than or equal to (\>=) 5000 copies/mL (c/mL). * Confirmed screening CD4+ T-cell count \>= 350 cells per cubic millimeter (cells/mm3). * Antiretroviral naïve: No Antiretroviral therapy (ARTs) (in combination or monotherapy) received after the diagnosis of HIV-1 infection. * Body weight \>= 50 kg to less than or equal to (\<=) 115 kg. * Male and/or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. All participants participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g. male condom) and on the risk of HIV transmission to an uninfected partner; a. Participants who are female at birth are eligible to participate if at least one of the following conditions applies: Not Pregnant or breastfeeding and at least one of the following conditions applies: Is not a participant of childbearing potential (POCBP). OR Is a POCBP and using an acceptable contraceptive method during the intervention period (at a minimum until after the last dose of study intervention). The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A POCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) on Day 1, prior to the first dose of study intervention. If a urine test cannot be confirmed as negative (example \[e.g.\], an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. * Corrected QT interval (QTc) Interval \<= 450 milliseconds (msec) * Capable of giving signed informed consent.
Exclusion criteria
* Participants with primary HIV infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion. * Participants who are pregnant, breastfeeding, plan to become pregnant or breastfeed during the study. * The participant has an underlying skin disease or disorder (example i.e. infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) that would interfere with assessment of injection sites. * Known history of cirrhosis with or without viral hepatitis co-infection. * History of clinically relevant hepatitis within last 6 months. * Evidence of Hepatitis B virus (HBV) infection based on the results of testing at screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and negative for HBV DNA are not excluded. * Participants with Hepatitis C co-infection. * Untreated syphilis infection (positive rapid plasma reagin \[RPR\] at screening) without documentation of treatment. Participants who are one month post completed treatment are eligible if recruitment is open. Rescreening is allowed after treatment. * Prior receipt of licensed or investigational monoclonal antibody. * Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease except cutaneous Kaposi's sarcoma not requiring systemic therapy. * Known or suspected moderate or severe hepatic impairment (Class C as determined by Child-Pugh Classification) coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease at the discretion of the investigator. * Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the study medical monitor for inclusion of the participant prior to randomization. * Any pre-existing physical or mental condition which, in the opinion of the investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations, or which may compromise the safety of the participant. * Participants with substance abuse disorders or social restraints that the investigator considers to be possible deterrents to successful completion of the study. * Participants who in the investigator's judgment, pose a significant suicidality risk. Participants' history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk. * History of sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. * Any condition which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs, combination ART or render the participant unable to take oral medication. * Participants with a positive Corona Virus Disease 2019 (COVID-19) test at Screening. Participants with known COVID-19 positive contacts within the past 14 days, or with symptoms suggestive of active COVID-19 (fever, cough, myalgias, shortness of breath, loss of taste or smell), should be excluded. Participants who remain symptom-free for at least 14 days after a COVID-19 exposure are allowed. * Has received any HIV-1 immunotherapeutic vaccine or prophylactic vaccine. * Treatment with any of the following agents within 28 days of screening: radiation therapy; cytotoxic chemotherapeutic agents; any systemic immune suppressant; * Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP. * Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication. * Participant enrolled in a prior or concurrent clinical study that includes a drug intervention within the last 30 days. * Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's inclusion in the study of an investigational compound. * Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result. * ALT \>= 3 times the upper limit of normal (ULN). * Creatinine clearance of \<50 mL/minute/1.73 meter\^2) via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. * The participant has a tattoo or other dermatological condition overlying potential injection sites which may interfere with interpretation of injection site reactions or administration of GSK3810109A.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Baseline (Day 1) and up to Day 84 or end of 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. |
| Number of Participants With Adverse Events (AEs) - Monotherapy Phase | Up to Day 84 or end of 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. |
| 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 | Baseline (Day 1) and up to Day 84 or end of 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. |
| Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Up to Day 84 or end of 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. |
| Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase | Up to Day 84 or end of 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | From Day 1 (Baseline) and up to Day 84 or end of 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. |
| Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | Up to Week 48 (SOC Phase) | Blood samples were collected as prespecified. CD4+ and CD8+ T cell counts were assessed using flow cytometry. |
| Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | Up to Day 84 or end of Monotherapy Phase (compared with baseline [Day 1]) | 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. |
| Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | Up to Week 48 (SOC Phase) | Blood samples were collected as prespecified. CD4+ and CD8+ T cell counts were assessed using flow cytometry. |
| Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase | At Day 14 | Blood samples were collected at indicated time point for pharmacokinetic analysis of GSK3810109A. |
| Number of Participants With Positive ADAs Against GSK3810109A - SOC Phase | At Week 48 (SOC Phase) | Serum samples were collected to analyze the presence of ADAs against GSK3810109A using validated immunoassays. |
| Titers of Positive ADAs Against GSK3810109A - Monotherapy Phase | At Day 84 or end of 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. |
| Titers of Positive ADAs Against GSK3810109A - SOC Phase | At Week 48 (SOC Phase) | Serum samples were collected to analyze the presence of ADAs against GSK3810109A using validated immunoassays. |
| Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | At Day 1 and Day 84 or end of 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase | Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3810109A. |
| Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase | Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14 | Cmax is defined as maximum observed concentration of GSK3810109A. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase | Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14 | Tmax is defined as time to reach Cmax |
| Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Baseline (Day 1) and up to Day 84 or end of 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. |
Countries
Argentina, Brazil, Canada, Mexico, Peru, United States
Participant flow
Recruitment details
62 unique participants were enrolled in the study including one participant that was re-screened. This re-screened participant signed two different informed consent forms, therefore this participant was counted as enrolling twice.
Pre-assignment details
Monotherapy phase had 2 parts (Part 1 and 2) where participants received GSK3810109A. All participants who completed monotherapy phase entered standard of care (SOC) follow-up phase to receive a regimen of dolutegravir + lamivudine.
Participants by arm
| Arm | Count |
|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) Participants with human immunodeficiency viruses-1 (HIV-1) received GSK3810109A as a single intravenous (IV) infusion of 40 milligrams per kilogram (mg/kg) dose based on individual bodyweight on Day 1 in part 1. | 8 |
| Part 1: GSK3810109A 280 mg IV Participants with HIV-1 received GSK3810109A as a single IV infusion of 280 mg dose on Day 1 in part 1. | 6 |
| Part 2: GSK3810109A 700 mg IV Participants with HIV-1 received GSK3810109A as a single IV infusion of 700 mg dose on Day 1 in part 2. This included dose level determined based on the data of part 1. | 16 |
| Part 2: GSK3810109A 70 mg IV Participants with HIV-1 received GSK3810109A as a single IV infusion of 70 mg dose on Day 1 in part 2. This included dose level determined based on the data of part 1. | 16 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) Participants with HIV-1 received GSK3810109A as a subcutaneous (SC) injection of total 700 mg dose administered as three equally divided SC injections of 2.33 mL each (approximately 7 mL) in quick succession at same time on Day 1 in part 2. This included dose level determined based on the data of part 1. | 16 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| SOC Follow-up (SOC Day 1 to 48 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| SOC Follow-up (SOC Day 1 to 48 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Total | Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Part 2: GSK3810109A 70 mg IV | Part 2: GSK3810109A 700 mg IV | Part 1: GSK3810109A 280 mg IV |
|---|---|---|---|---|---|---|
| Age, Continuous | 34.3 YEARS STANDARD_DEVIATION 9.39 | 32.2 YEARS STANDARD_DEVIATION 10.62 | 31.5 YEARS STANDARD_DEVIATION 11.08 | 32.3 YEARS STANDARD_DEVIATION 10.33 | 31.2 YEARS STANDARD_DEVIATION 10.46 | 34.0 YEARS STANDARD_DEVIATION 14.83 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 11 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 5 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White - Arabic/ North African Heritage | 0 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White - White/ Caucasian/ European Heritage | 6 Participants | 38 Participants | 9 Participants | 8 Participants | 10 Participants | 5 Participants |
| Sex/Gender, Customized Female | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Sex/Gender, Customized Male | 8 Participants | 58 Participants | 15 Participants | 16 Participants | 14 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 8 | 0 / 6 | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 7 / 8 | 4 / 6 | 9 / 16 | 8 / 16 | 11 / 16 | 8 / 8 | 3 / 6 | 12 / 16 | 13 / 16 | 14 / 16 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 16 | 0 / 16 | 0 / 16 | 1 / 8 | 0 / 6 | 3 / 16 | 2 / 16 | 4 / 16 |
Outcome results
Primary
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
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Baseline (Day 1) | 12258.5 Copies per milliliter (copies/mL) |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Maximum decline from baseline (up to Day 84/end of Monotherapy Phase) | -12014.5 Copies per milliliter (copies/mL) |
| Part 1: GSK3810109A 280 mg IV | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Baseline (Day 1) | 30833.0 Copies per milliliter (copies/mL) |
| Part 1: GSK3810109A 280 mg IV | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Maximum decline from baseline (up to Day 84/end of Monotherapy Phase) | -26826.5 Copies per milliliter (copies/mL) |
| Part 2: GSK3810109A 700 mg IV | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Baseline (Day 1) | 25466.0 Copies per milliliter (copies/mL) |
| Part 2: GSK3810109A 700 mg IV | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Maximum decline from baseline (up to Day 84/end of Monotherapy Phase) | -25966.0 Copies per milliliter (copies/mL) |
| Part 2: GSK3810109A 70 mg IV | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Maximum decline from baseline (up to Day 84/end of Monotherapy Phase) | -14720.5 Copies per milliliter (copies/mL) |
| Part 2: GSK3810109A 70 mg IV | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Baseline (Day 1) | 25689.5 Copies per milliliter (copies/mL) |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Baseline (Day 1) | 23146.0 Copies per milliliter (copies/mL) |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase | Maximum decline from baseline (up to Day 84/end of Monotherapy Phase) | -12584.0 Copies per milliliter (copies/mL) |
Primary
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
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Number of Participants With Adverse Events (AEs) - Monotherapy Phase | 7 Participants |
| Part 1: GSK3810109A 280 mg IV | Number of Participants With Adverse Events (AEs) - Monotherapy Phase | 4 Participants |
| Part 2: GSK3810109A 700 mg IV | Number of Participants With Adverse Events (AEs) - Monotherapy Phase | 9 Participants |
| Part 2: GSK3810109A 70 mg IV | Number of Participants With Adverse Events (AEs) - Monotherapy Phase | 8 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Number of Participants With Adverse Events (AEs) - Monotherapy Phase | 11 Participants |
Primary
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
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase | 0 Participants |
Primary
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
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Clinically Significant | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Not Clinically Significant | 3 Participants |
| Part 1: GSK3810109A 280 mg IV | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Clinically Significant | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Not Clinically Significant | 2 Participants |
| Part 2: GSK3810109A 700 mg IV | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Clinically Significant | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Not Clinically Significant | 3 Participants |
| Part 2: GSK3810109A 70 mg IV | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Not Clinically Significant | 4 Participants |
| Part 2: GSK3810109A 70 mg IV | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Clinically Significant | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Clinically Significant | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase | Abnormal - Not Clinically Significant | 7 Participants |
Primary
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.
Time frame: Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | ALT, Baseline, Grade 0 | 8 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | AST, Baseline, Grade 1 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | AST, Baseline, Grade 0 | 8 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | AST, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 1 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | ALT, Baseline, Grade 2 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | AST, Baseline, Grade 4 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | ALT, Baseline, Grade 3 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | AST, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 1 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | AST, Baseline, Grade 3 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | ALT, Baseline, Grade 4 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | ALT, Baseline, Grade 1 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | AST, Baseline, Grade 2 | 0 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | ALT, Baseline, Grade 4 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | ALT, Baseline, Grade 3 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | ALT, Baseline, Grade 1 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | AST, Baseline, Grade 0 | 6 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | AST, Baseline, Grade 1 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | ALT, Baseline, Grade 0 | 6 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | AST, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | AST, Baseline, Grade 3 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | AST, Baseline, Grade 2 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | ALT, Baseline, Grade 2 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | AST, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | 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 | AST, Baseline, Grade 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | ALT, Baseline, Grade 0 | 15 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | ALT, Baseline, Grade 1 | 1 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | ALT, Baseline, Grade 2 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | ALT, Baseline, Grade 3 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | ALT, Baseline, Grade 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | AST, Baseline, Grade 0 | 15 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | AST, Baseline, Grade 1 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | AST, Baseline, Grade 2 | 1 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | AST, Baseline, Grade 3 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | AST, Baseline, Grade 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | AST, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 1 Participants |
| Part 2: GSK3810109A 700 mg IV | 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 | AST, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 1 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | AST, Baseline, Grade 1 | 1 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | ALT, Baseline, Grade 4 | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | AST, Baseline, Grade 2 | 1 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | ALT, Baseline, Grade 3 | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | ALT, Baseline, Grade 0 | 12 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | AST, Baseline, Grade 3 | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | ALT, Baseline, Grade 2 | 2 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | AST, Baseline, Grade 4 | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | ALT, Baseline, Grade 1 | 2 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | AST, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | AST, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | 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 | AST, Baseline, Grade 0 | 14 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | AST, Worst Case Post-Baseline, Increase to Grades 3 to 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | AST, Baseline, Grade 1 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | ALT, Baseline, Grade 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | AST, Baseline, Grade 0 | 16 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | ALT, Baseline, Grade 0 | 15 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | AST, Baseline, Grade 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | AST, Baseline, Grade 2 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | ALT, Baseline, Grade 3 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | ALT, Baseline, Grade 1 | 1 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | ALT, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | AST, Worst Case Post-Baseline, Increase to Grades 2 to 4 | 1 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | AST, Baseline, Grade 3 | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | 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 | ALT, Baseline, Grade 2 | 0 Participants |
Secondary
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)
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 (SOC Phase) | 685.9 Cells per cubic milimeter | Standard Deviation 308.89 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 (SOC Phase) | 500.5 Cells per cubic milimeter | Standard Deviation 211.17 |
| Part 1: GSK3810109A 280 mg IV | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 (SOC Phase) | 601.0 Cells per cubic milimeter | Standard Deviation 44.74 |
| Part 1: GSK3810109A 280 mg IV | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 (SOC Phase) | 738.4 Cells per cubic milimeter | Standard Deviation 213.22 |
| Part 2: GSK3810109A 700 mg IV | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 (SOC Phase) | 684.9 Cells per cubic milimeter | Standard Deviation 286.6 |
| Part 2: GSK3810109A 700 mg IV | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 (SOC Phase) | 580.9 Cells per cubic milimeter | Standard Deviation 165.29 |
| Part 2: GSK3810109A 70 mg IV | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 (SOC Phase) | 671.3 Cells per cubic milimeter | Standard Deviation 180.25 |
| Part 2: GSK3810109A 70 mg IV | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 (SOC Phase) | 856.0 Cells per cubic milimeter | Standard Deviation 325.04 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 (SOC Phase) | 816.6 Cells per cubic milimeter | Standard Deviation 364.4 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 (SOC Phase) | 723.9 Cells per cubic milimeter | Standard Deviation 300.24 |
Secondary
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
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 360.5 Cells per cubic milimeter | Standard Deviation 166.54 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 852.0 Cells per cubic milimeter | Standard Deviation 441.83 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/End of Monotherapy Phase | 837.9 Cells per cubic milimeter | Standard Deviation 482.68 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase | 392.3 Cells per cubic milimeter | Standard Deviation 196.16 |
| Part 1: GSK3810109A 280 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase | 443.0 Cells per cubic milimeter | Standard Deviation 155.17 |
| Part 1: GSK3810109A 280 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 884.5 Cells per cubic milimeter | Standard Deviation 389.42 |
| Part 1: GSK3810109A 280 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 412.8 Cells per cubic milimeter | Standard Deviation 120.85 |
| Part 1: GSK3810109A 280 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/End of Monotherapy Phase | 869.8 Cells per cubic milimeter | Standard Deviation 376.86 |
| Part 2: GSK3810109A 700 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 427.3 Cells per cubic milimeter | Standard Deviation 187.22 |
| Part 2: GSK3810109A 700 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase | 424.0 Cells per cubic milimeter | Standard Deviation 171.33 |
| Part 2: GSK3810109A 700 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 781.8 Cells per cubic milimeter | Standard Deviation 303.75 |
| Part 2: GSK3810109A 700 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/End of Monotherapy Phase | 744.0 Cells per cubic milimeter | Standard Deviation 267.73 |
| Part 2: GSK3810109A 70 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase | 412.9 Cells per cubic milimeter | Standard Deviation 98.5 |
| Part 2: GSK3810109A 70 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 1161.3 Cells per cubic milimeter | Standard Deviation 697.24 |
| Part 2: GSK3810109A 70 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 467.3 Cells per cubic milimeter | Standard Deviation 194.45 |
| Part 2: GSK3810109A 70 mg IV | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/End of Monotherapy Phase | 993.1 Cells per cubic milimeter | Standard Deviation 394.84 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase | 462.4 Cells per cubic milimeter | Standard Deviation 276.72 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/End of Monotherapy Phase | 765.9 Cells per cubic milimeter | Standard Deviation 296.18 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 898.0 Cells per cubic milimeter | Standard Deviation 348.48 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 476.7 Cells per cubic milimeter | Standard Deviation 180.28 |
Secondary
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
Population: Analysis was performed on the Pharmacokinetic (PK) population, which included all participants in the Safety population who had at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values with the actual dose and PK sampling time will be considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase | 5346.3194 Day *microgram/millilitre (day*ug/mL) | Geometric Coefficient of Variation 29.6508 |
| Part 1: GSK3810109A 280 mg IV | Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase | 690.8944 Day *microgram/millilitre (day*ug/mL) | Geometric Coefficient of Variation 53.2785 |
| Part 2: GSK3810109A 700 mg IV | Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase | 1181.1688 Day *microgram/millilitre (day*ug/mL) | Geometric Coefficient of Variation 24.499 |
| Part 2: GSK3810109A 70 mg IV | Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase | 212.6213 Day *microgram/millilitre (day*ug/mL) | Geometric Coefficient of Variation 79.1478 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase | 493.0579 Day *microgram/millilitre (day*ug/mL) | Geometric Coefficient of Variation 55.0909 |
Secondary
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])
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 360.5 Cells per cubic milimeter | Standard Deviation 166.54 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase (compared with baseline) | 31.8 Cells per cubic milimeter | Standard Deviation 48.27 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 852.0 Cells per cubic milimeter | Standard Deviation 441.83 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/end of Monotherapy Phase (compared with baseline) | -14.1 Cells per cubic milimeter | Standard Deviation 213.24 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 412.8 Cells per cubic milimeter | Standard Deviation 120.85 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/end of Monotherapy Phase (compared with baseline) | -14.7 Cells per cubic milimeter | Standard Deviation 281.75 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase (compared with baseline) | 30.2 Cells per cubic milimeter | Standard Deviation 79.83 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 884.5 Cells per cubic milimeter | Standard Deviation 389.42 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/end of Monotherapy Phase (compared with baseline) | -37.8 Cells per cubic milimeter | Standard Deviation 206.05 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase (compared with baseline) | -3.3 Cells per cubic milimeter | Standard Deviation 125.78 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 781.8 Cells per cubic milimeter | Standard Deviation 303.75 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 427.3 Cells per cubic milimeter | Standard Deviation 187.22 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 467.3 Cells per cubic milimeter | Standard Deviation 194.45 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase (compared with baseline) | -54.3 Cells per cubic milimeter | Standard Deviation 121.18 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/end of Monotherapy Phase (compared with baseline) | -168.2 Cells per cubic milimeter | Standard Deviation 401.82 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 1161.3 Cells per cubic milimeter | Standard Deviation 697.24 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Day 84/end of Monotherapy Phase (compared with baseline) | -105.7 Cells per cubic milimeter | Standard Deviation 246.85 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 898.0 Cells per cubic milimeter | Standard Deviation 348.48 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Day 84/end of Monotherapy Phase (compared with baseline) | -19.6 Cells per cubic milimeter | Standard Deviation 166.64 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 476.7 Cells per cubic milimeter | Standard Deviation 180.28 |
Secondary
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)
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 360.5 Cells per cubic milimeter | Standard Deviation 166.54 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 of SOC Phase (compared with baseline) | 140.0 Cells per cubic milimeter | Standard Deviation 91.08 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 852.0 Cells per cubic milimeter | Standard Deviation 441.83 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 of SOC Phase (compared with baseline) | -166.1 Cells per cubic milimeter | Standard Deviation 274.92 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 412.8 Cells per cubic milimeter | Standard Deviation 120.85 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 of SOC Phase (compared with baseline) | -159.4 Cells per cubic milimeter | Standard Deviation 275.37 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 of SOC Phase (compared with baseline) | 180.4 Cells per cubic milimeter | Standard Deviation 114.37 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 884.5 Cells per cubic milimeter | Standard Deviation 389.42 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 of SOC Phase (compared with baseline) | -119.7 Cells per cubic milimeter | Standard Deviation 198.49 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 of SOC Phase (compared with baseline) | 134.9 Cells per cubic milimeter | Standard Deviation 205.13 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 781.8 Cells per cubic milimeter | Standard Deviation 303.75 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 427.3 Cells per cubic milimeter | Standard Deviation 187.22 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 467.3 Cells per cubic milimeter | Standard Deviation 194.45 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 of SOC Phase (compared with baseline) | 233.8 Cells per cubic milimeter | Standard Deviation 174.02 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 of SOC Phase (compared with baseline) | -217.5 Cells per cubic milimeter | Standard Deviation 490.1 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 1161.3 Cells per cubic milimeter | Standard Deviation 697.24 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Week 48 of SOC Phase (compared with baseline) | -81.4 Cells per cubic milimeter | Standard Deviation 230.95 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD8+, Baseline (Day 1 (Monotherapy Phase) | 898.0 Cells per cubic milimeter | Standard Deviation 348.48 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Week 48 of SOC Phase (compared with baseline) | 247.3 Cells per cubic milimeter | Standard Deviation 230.95 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase | CD4+, Baseline (Day 1 (Monotherapy Phase) | 476.7 Cells per cubic milimeter | Standard Deviation 180.28 |
Secondary
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
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed. Only participants in the IV dosing group with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Baseline (Day 1) | 4.139 Log10 copies per milliliter (copies/mL) | Standard Deviation 0.6433 |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Change from baseline (up to Day 84 or end of Monotherapy Phase) | 0.091 Log10 copies per milliliter (copies/mL) | Standard Deviation 0.2359 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Change from baseline (up to Day 84 or end of Monotherapy Phase) | -0.357 Log10 copies per milliliter (copies/mL) | Standard Deviation 0.4191 |
| Part 1: GSK3810109A 280 mg IV | Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Baseline (Day 1) | 4.493 Log10 copies per milliliter (copies/mL) | Standard Deviation 0.48 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Baseline (Day 1) | 4.465 Log10 copies per milliliter (copies/mL) | Standard Deviation 0.3594 |
| Part 2: GSK3810109A 700 mg IV | Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Change from baseline (up to Day 84 or end of Monotherapy Phase) | -0.110 Log10 copies per milliliter (copies/mL) | Standard Deviation 0.194 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Baseline (Day 1) | 4.582 Log10 copies per milliliter (copies/mL) | Standard Deviation 0.6144 |
| Part 2: GSK3810109A 70 mg IV | Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase | Change from baseline (up to Day 84 or end of Monotherapy Phase) | -0.179 Log10 copies per milliliter (copies/mL) | Standard Deviation 0.4319 |
95% CI: [-2.225, -1.472]
95% CI: [15.866, 121.29]
95% CI: [0.145, 0.368]
Secondary
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
Population: Analysis was performed on the PK population, which included all participants in the Safety population who had at least 1 non-missing PK assessment (NQ values with the actual dose and PK sampling time will be considered as non-missing values).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase | 1131.5000 Microgram/millilitre (μg/mL) | Standard Deviation 329.91168 |
| Part 1: GSK3810109A 280 mg IV | Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase | 131.1500 Microgram/millilitre (μg/mL) | Standard Deviation 86.65425 |
| Part 2: GSK3810109A 700 mg IV | Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase | 243.0625 Microgram/millilitre (μg/mL) | Standard Deviation 57.37301 |
| Part 2: GSK3810109A 70 mg IV | Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase | 42.7688 Microgram/millilitre (μg/mL) | Standard Deviation 54.32691 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase | 45.0938 Microgram/millilitre (μg/mL) | Standard Deviation 20.4893 |
Secondary
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)
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Number of Participants With Positive ADAs Against GSK3810109A - SOC Phase | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | Number of Participants With Positive ADAs Against GSK3810109A - SOC Phase | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | Number of Participants With Positive ADAs Against GSK3810109A - SOC Phase | 1 Participants |
| Part 2: GSK3810109A 70 mg IV | Number of Participants With Positive ADAs Against GSK3810109A - SOC Phase | 2 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Number of Participants With Positive ADAs Against GSK3810109A - SOC Phase | 0 Participants |
Secondary
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
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Day 84/End of Monotherapy Phase | 1 Participants |
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Baseline (Day 1) | 0 Participants |
| Part 1: GSK3810109A 280 mg IV | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Day 84/End of Monotherapy Phase | 2 Participants |
| Part 1: GSK3810109A 280 mg IV | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Baseline (Day 1) | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Baseline (Day 1) | 0 Participants |
| Part 2: GSK3810109A 700 mg IV | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Day 84/End of Monotherapy Phase | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Baseline (Day 1) | 0 Participants |
| Part 2: GSK3810109A 70 mg IV | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Day 84/End of Monotherapy Phase | 3 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Day 84/End of Monotherapy Phase | 0 Participants |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase | Baseline (Day 1) | 0 Participants |
Secondary
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
Population: Analysis was performed on the PK population, which included all participants in the Safety population who had at least 1 non-missing PK assessment (NQ values with the actual dose and PK sampling time will be considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase | 221.45 μg/mL | Geometric Coefficient of Variation 23.76 |
| Part 1: GSK3810109A 280 mg IV | Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase | 27.49 μg/mL | Geometric Coefficient of Variation 49.24 |
| Part 2: GSK3810109A 700 mg IV | Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase | 55.30 μg/mL | Geometric Coefficient of Variation 22.08 |
| Part 2: GSK3810109A 70 mg IV | Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase | 7.98 μg/mL | Geometric Coefficient of Variation 89.7 |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase | 29.52 μg/mL | Geometric Coefficient of Variation 54.3 |
Secondary
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
Population: Analysis was performed on the PK population, which included all participants in the Safety population who had at least 1 non-missing PK assessment (NQ values with the actual dose and PK sampling time will be considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase | 0.0385 Days |
| Part 1: GSK3810109A 280 mg IV | Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase | 0.1233 Days |
| Part 2: GSK3810109A 700 mg IV | Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase | 0.0340 Days |
| Part 2: GSK3810109A 70 mg IV | Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase | 0.0278 Days |
| Part 2: GSK3810109A 700 mg Subcutaneously (SC) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase | 5.9177 Days |
Secondary
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
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV) | Titers of Positive ADAs Against GSK3810109A - Monotherapy Phase | 40 Titers |
| Part 1: GSK3810109A 280 mg IV | Titers of Positive ADAs Against GSK3810109A - Monotherapy Phase | 60 Titers |
| Part 2: GSK3810109A 70 mg IV | Titers of Positive ADAs Against GSK3810109A - Monotherapy Phase | 80 Titers |
Secondary
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)
Population: The analysis was performed on the safety population, which included all participants who received at least one dose of study treatment. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2: GSK3810109A 700 mg IV | Titers of Positive ADAs Against GSK3810109A - SOC Phase | 40 Titers |
| Part 2: GSK3810109A 70 mg IV | Titers of Positive ADAs Against GSK3810109A - SOC Phase | 160 Titers |