Colitis, Ulcerative, Multiple Sclerosis
Conditions
Keywords
Anti-Drug Antibodies, Double-blind, GSK3888130B, Pharmacodynamics, Pharmacokinetics, Single Dose Escalation
Brief summary
This is a first time in human study designed to assess the safety, tolerability, pharmacokinetics and PD of GSK3888130B over a range of dose levels in healthy participants.
Interventions
DRUGGSK3888130B
GSK3888130B will be administered.
DRUGPlacebo
Placebo will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This will be a double-blind study.
Intervention model description
Participants will be randomized to receive either GSK3888130B or placebo in single ascending dose cohorts.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to 55 years of age inclusive. * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * Participants with a confirmed positive vaccination status for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines administered at least 30 days prior to dosing in the study. * SARS-CoV-2 screening test negative as per local guidance. * Participants with history of current/seasonal vaccination status for influenza or who consent to receive influenza vaccine at least 30 days prior to dosing, if study dosing is during influenza season (1st October to 30th April). * Body weight greater than or equal to (\>=) 50 kilograms (kg) and body mass index (BMI) within the range 19.5-32 kilograms per square meter (kg/m\^2) (inclusive). * Male and/or female of non-childbearing potential * Capable of giving signed informed consent.
Exclusion criteria
* Prior medical history of anaphylaxis. * Immunodeficiency or autoimmunity assessed by medical history. * A history of recurrent infections. * Treatment of a chronic infection within 3 months prior to the first dose of study drug. * Any acute infection (including upper respiratory tract infections and urinary tract infections) which has not fully resolved within four weeks of dosing * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy. * Current or chronic history of liver disease or known hepatic or biliary abnormalities. * Participants with a history of renal disease or renal abnormalities. * A clinically significant abnormality in the 12-lead ECG performed at screening. * A clinically significant abnormality in the Holter monitor performed at screening. * History of malignancy, including malignant or non-malignant skin cancer. * Participants with known SARS-CoV-2 positive contacts in the past 14 days. * Prior moderate/severe SARS-CoV-2 infection requiring oxygen supplementation or admission to hospital. * Antibiotics or antiviral therapy within 30 days of dosing. * Receipt of live vaccination within 30 days of dosing or plan to receive live vaccination during the study. * Use of prescription drugs or non-prescription drugs, including non-steroidal anti inflammatory drug (NSAIDs), within 7 days prior to dosing, if in the opinion of the Investigator (in consultation with the GlaxoSmithKline \[GSK\] Medical Monitor if required) the medication will interfere with the study procedures or compromise participant safety. * The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day of the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Exposure to more than 4 new chemical entities within 12 months prior to dosing. * A positive drug/alcohol test at screening or Day -1 * The participant is at high-risk of Mycobacterium tuberculosis (MTB) infection in the opinion of the Investigator. * History of asthma, allergic rhinitis or atopic dermatitis defined by the need for intermittent or continuous therapy or any other significant allergies that, in the opinion of the investigator contraindicates their participation. * History of severe adverse reaction to local anesthetic. * Presence of keloids or history of keloids. * Prothrombin time (PT) or activated partial thromboplastin time (aPTT) \>1.5x upper limit of normal (ULN) at screening. * History or presence of excessive bleeding or coagulation disorders that in the opinion of the Investigator poses a safety risk with regards to participation in the trial. * Presence of tattoos, naevi or other skin abnormalities on the volar forearm Fitzpatrick skin color grades V in the opinion of the investigator, interfere with study assessments * Participating, within 7 days of dosing, in recreational sun-bathing, or use of sunbed, on the area of the skin from wrist to shoulder inclusive. * Current smoker or user of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) during or within 30 days prior to study participation. * An average weekly intake of \>14 units of alcohol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 160 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. |
| Number of Participants With Clinically Significant Changes in Hematology Results | Up to 85 days | Blood samples were collected for analysis of following hematology parameters: Basophils, Eosinophils, Hematocrit, Hemoglobin (Hg), Lymphocytes, Mean corpuscular Hg, Mean corpuscular volume, Monocytes, Platelet count, Red blood cell count, Reticulocytes, Total Neutrophils, and White blood cells count (WBC). Number of participants with clinically significant changes in hematology were reported. Clinical significance was determined by the investigator. |
| Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Baseline (Day 1) and up to 85 days | Blood samples were collected for the analysis of CD4+ T Cell Counts. The CD4+ T Cell Counts were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE). Grade 0: Above 0.5\*10\^9 cells/Liter (L), Grade 1: \<0.5 to 0.2\*10\^9 cells/L, Grade 2: \<0.2 to 0.05\*10\^9 cells/L, Grade 3: Below 0.05\*10\^9 cells/L. Baseline was defined as the latest pre-dose assessment. An increase was defined as an increase in grade relative to Baseline grade. Any worst-case post Baseline increase to Grade 1, Grade 2 and Grade 3 are presented. |
| Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Baseline (Day 1) and up to 85 days | Blood samples were collected for the analysis of Creatinine. Creatinine was graded according to the NCI-CTCAE. Grade 0: \<1.5\* Baseline, or increase from Baseline \<26 micromoles per liter (umol/L), Grade 1: 1.5 to 1.9\* Baseline, or increase from Baseline \>=26 umol/L, Grade 2: 2.0 to 2.9\* Baseline, Grade 3: \>=3.0\* Baseline, or \>=354 umol/L. Baseline was defined as the latest pre-dose assessment. An increase was defined as an increase in grade relative to Baseline grade. Any worst-case post Baseline increase to Grade 1, Grade 2 and Grade 3 are presented. |
| Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | Up to 85 days | Blood samples were collected for analysis of following clinical chemistry parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Calcium, Total and Direct bilirubin, Glucose, Potassium, Sodium, Total protein, Lactate dehydrogenase, Haptoglobins and Urea. Number of participants with clinically significant changes in clinical chemistry were reported. Clinical significance was determined by the investigator. |
| Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Baseline (Day 1) and up to 85 days | Urine samples were collected for analysis of Specific gravity, potential of hydrogen (pH), glucose, protein, erythrocytes, ketones, bilirubin, urobilinogen, nitrite, and leukocyte in urine by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Baseline was defined as the latest pre-dose assessment. Number of participants with worst-case any increase in urinalysis results post-Baseline relative to Baseline has been presented. |
| Number of Participants With Clinically Significant Changes in Vital Sign Results | Up to 85 days | Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Clinical significance was determined by the investigator. |
| Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Baseline (Day 1), Day 15 and Day 85 | VZV-Nucleic acid from blood samples were extracted using the QIASymphony SP followed by TaqMan real time polymerase chain reaction (PCR) for amplification and detection. Murine cytomegalovirus (mCMV) was used as an internal control (IC) and was introduced during the extraction process. CMV-Nucleic acid was extracted using the QIASymphony SP/AS followed by automated set up of Artus real time PCR using the Rotor-Gene Q for amplification and detection. Baseline was defined as the latest pre-dose assessment. Number of participants with Positive CMV DNA and VZV DNA has been presented. |
| Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Day 15 and Day 85 | EBV DNA was assessed and qualitative data has been presented. Data has been categorized into 'Positive \>=LLQ' and 'Positive \< LLQ'. LLQ is lower limit of quantification. Participants who had EBV DNA values \>=LLQ were categorized as 'Positive \>=LLQ'. This represents a positive result that is above the assay limit of quantification. Participants who had EBV DNA values \<LLQ were categorized as 'Positive \<LLQ'. This represents a positive result that is below the assay limit of quantification. Baseline was defined as the latest pre-dose assessment. |
| Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Up to 85 days | Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT corrected interval. Abnormal findings were categorized as clinically significant (CS) and 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration. |
| Tmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| t1/2 of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration. |
| t1/2 of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following intravenous administration. Pharmacokinetic (PK) Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values). |
| Clearance Factor (CL/F) of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration. |
| CL of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1), Day 15, Day 29, Day 57 and Day 85 | Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Baseline was defined as the latest pre-dose assessment. |
| Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | Baseline (Day 1) and up to 8 hours | Free IL-7 levels were derived from total IL-7 and total GSK3888130B concentrations (named as Derived Free IL-7) over time using a nonlinear mixed effects modelling approach. A target-mediated drug disposition model was used to fit the total IL-7 and total GSK3888130B assay concentration data to derive the free-IL-7 concentrations. Peak reduction relative to Baseline (Percent change) was calculated for each participant as; Peak reduction = (1 - minimum \[Free IL7/IL7 Baseline\])\*100. Baseline was defined as the latest pre-dose assessment. |
| Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) and Day 15 | Blood samples were collected at indicated time points to measure Bcl-2 Expression in CD4+ T Cells as median fluorescence intensity (MdFI). Baseline was defined as the latest pre-dose assessment. MdFI values as a measure of Bcl-2 expression in CD4+ T cells was measured by flow cytometry. Placebo arms were combined as pre-specified in reporting and analysis plan. |
| Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following subcutaneous administration. |
| Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following intravenous administration. Pharmacokinetic (PK) Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values). |
| Area Under the Concentration-time Curve From Time Zero to Time t (AUC[0 to t]) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| AUC(0 to t) for Dose Levels 3 and 5 Subcutaneous Administration | Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration. |
| AUC(0 to t) for Dose Levels 6 and 7 Intravenous Administration | Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| Cmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration. |
| Cmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
| Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration. |
Countries
United Kingdom
Participant flow
Pre-assignment details
A total 54 participants were enrolled in this study. Placebo arms were combined as pre-specified in reporting and analysis plan. Dosing information (dosage strengths) has not been disclosed as it is considered as company confidential information (CCI). Dose levels are presented as Dose levels 1 to 7 along with directionality of the dosage within each arm/group.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a placebo matching GSK3888130B either intravenous (IV) infusion or subcutaneous (SC) injection on Day 1. | 15 |
| GSK3888130B Dose Level 1 IV Participants received a single dose of GSK3888130B dose level 1, intravenous (IV) infusion on Day 1. Dose level 1 is the lowest dose level. | 3 |
| GSK3888130B Dose Level 2 IV Participants received a single dose of GSK3888130B dose level 2, IV infusion on Day 1. Dose level 2 is greater than dose level 1. | 3 |
| GSK3888130B Dose Level 3 SC Participants received a single dose of GSK3888130B dose level 3, subcutaneous (SC) injection on Day 1. Dose level 3 is greater than dose level 2. | 6 |
| GSK3888130B Dose Level 4 IV Participants received a single dose of GSK3888130B dose level 4, IV infusion on Day 1. Dose level 4 is greater than dose level 3. | 6 |
| GSK3888130B Dose Level 5 SC Participants received a single dose of GSK3888130B dose level 5, SC injection on Day 1. Dose level 5 is greater than dose level 4. | 6 |
| GSK3888130B Dose Level 6 IV Participants received a single dose of GSK3888130B dose level 6, IV infusion on Day 1. Dose level 6 is greater than dose level 5. | 9 |
| GSK3888130B Dose Level 7 IV Participants received a single dose of GSK3888130B dose level 7, IV infusion on Day 1. Dose level 7 is the highest dose level. | 6 |
| Total | 54 |
Baseline characteristics
| Characteristic | Placebo | GSK3888130B Dose Level 1 IV | GSK3888130B Dose Level 2 IV | GSK3888130B Dose Level 3 SC | GSK3888130B Dose Level 4 IV | GSK3888130B Dose Level 5 SC | GSK3888130B Dose Level 6 IV | GSK3888130B Dose Level 7 IV | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 40.3 YEARS STANDARD_DEVIATION 8.93 | 40.0 YEARS STANDARD_DEVIATION 7.94 | 48.3 YEARS STANDARD_DEVIATION 3.06 | 38.8 YEARS STANDARD_DEVIATION 8.75 | 41.2 YEARS STANDARD_DEVIATION 9.52 | 40.8 YEARS STANDARD_DEVIATION 7.7 | 38.7 YEARS STANDARD_DEVIATION 9.86 | 41.5 YEARS STANDARD_DEVIATION 11.57 | 40.6 YEARS STANDARD_DEVIATION 8.78 |
| Race/Ethnicity, Customized All Other Races | 15 Participants | 3 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 6 Participants | 54 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 3 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 6 Participants | 54 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 6 |
| other Total, other adverse events | 8 / 15 | 3 / 3 | 2 / 3 | 6 / 6 | 2 / 6 | 4 / 6 | 8 / 9 | 5 / 6 |
| serious Total, serious adverse events | 0 / 15 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Time frame: Up to 160 days
Population: Safety Population included all participants who received study intervention. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 8 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 8 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Clinical Chemistry Results
Blood samples were collected for analysis of following clinical chemistry parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Calcium, Total and Direct bilirubin, Glucose, Potassium, Sodium, Total protein, Lactate dehydrogenase, Haptoglobins and Urea. Number of participants with clinically significant changes in clinical chemistry were reported. Clinical significance was determined by the investigator.
Time frame: Up to 85 days
Population: Safety Population included all participants who received study intervention. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Clinically Significant Changes in Clinical Chemistry Results | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Hematology Results
Blood samples were collected for analysis of following hematology parameters: Basophils, Eosinophils, Hematocrit, Hemoglobin (Hg), Lymphocytes, Mean corpuscular Hg, Mean corpuscular volume, Monocytes, Platelet count, Red blood cell count, Reticulocytes, Total Neutrophils, and White blood cells count (WBC). Number of participants with clinically significant changes in hematology were reported. Clinical significance was determined by the investigator.
Time frame: Up to 85 days
Population: Safety Population included all participants who received study intervention. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Hematology Results | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Clinically Significant Changes in Hematology Results | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Clinically Significant Changes in Hematology Results | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Clinically Significant Changes in Hematology Results | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Clinically Significant Changes in Hematology Results | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Clinically Significant Changes in Hematology Results | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Clinically Significant Changes in Hematology Results | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Clinically Significant Changes in Hematology Results | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Sign Results
Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Clinical significance was determined by the investigator.
Time frame: Up to 85 days
Population: Safety Population included all participants who received study intervention. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Results | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Clinically Significant Changes in Vital Sign Results | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Clinically Significant Changes in Vital Sign Results | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Clinically Significant Changes in Vital Sign Results | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Clinically Significant Changes in Vital Sign Results | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Clinically Significant Changes in Vital Sign Results | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Clinically Significant Changes in Vital Sign Results | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Clinically Significant Changes in Vital Sign Results | 0 Participants |
Primary
Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA
VZV-Nucleic acid from blood samples were extracted using the QIASymphony SP followed by TaqMan real time polymerase chain reaction (PCR) for amplification and detection. Murine cytomegalovirus (mCMV) was used as an internal control (IC) and was introduced during the extraction process. CMV-Nucleic acid was extracted using the QIASymphony SP/AS followed by automated set up of Artus real time PCR using the Rotor-Gene Q for amplification and detection. Baseline was defined as the latest pre-dose assessment. Number of participants with Positive CMV DNA and VZV DNA has been presented.
Time frame: Baseline (Day 1), Day 15 and Day 85
Population: Safety Population included all participants who received study intervention. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 15 | 0 Participants |
| Placebo | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Baseline (Day 1) | 0 Participants |
| Placebo | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 85 | 0 Participants |
| Placebo | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Baseline (Day 1) | 0 Participants |
| Placebo | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 85 | 0 Participants |
| Placebo | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 85 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Day 15 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Cytomegalovirus DNA, Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA | Varicella Zoster Virus DNA, Day 15 | 0 Participants |
Primary
Number of Participants With Positive Epstein-Barr Virus (EBV) DNA
EBV DNA was assessed and qualitative data has been presented. Data has been categorized into 'Positive \>=LLQ' and 'Positive \< LLQ'. LLQ is lower limit of quantification. Participants who had EBV DNA values \>=LLQ were categorized as 'Positive \>=LLQ'. This represents a positive result that is above the assay limit of quantification. Participants who had EBV DNA values \<LLQ were categorized as 'Positive \<LLQ'. This represents a positive result that is below the assay limit of quantification. Baseline was defined as the latest pre-dose assessment.
Time frame: Baseline (Day 1), Day 15 and Day 85
Population: Safety Population included all participants who received study intervention. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive < LLQ | 0 Participants |
| Placebo | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive >= LLQ | 0 Participants |
| Placebo | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive >= LLQ | 1 Participants |
| Placebo | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive < LLQ | 0 Participants |
| Placebo | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive >= LLQ | 2 Participants |
| Placebo | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive < LLQ | 1 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive >= LLQ | 1 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive >= LLQ | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive < LLQ | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive >= LLQ | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive < LLQ | 1 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive >= LLQ | 1 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive >= LLQ | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive < LLQ | 2 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive >= LLQ | 1 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive < LLQ | 1 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive >= LLQ | 2 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Baseline (Day 1), Positive < LLQ | 1 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 85, Positive < LLQ | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Epstein-Barr Virus (EBV) DNA | Day 15, Positive >= LLQ | 0 Participants |
Primary
Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline
Urine samples were collected for analysis of Specific gravity, potential of hydrogen (pH), glucose, protein, erythrocytes, ketones, bilirubin, urobilinogen, nitrite, and leukocyte in urine by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Baseline was defined as the latest pre-dose assessment. Number of participants with worst-case any increase in urinalysis results post-Baseline relative to Baseline has been presented.
Time frame: Baseline (Day 1) and up to 85 days
Population: Safety Population included all participants who received study intervention. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Urobilinogen | 0 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 0 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Nitrite | 0 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | pH | 12 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 1 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Bilirubin | 0 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Leukocytes | 0 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Specific Gravity | 8 Participants |
| Placebo | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Erythrocytes | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Bilirubin | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Leukocytes | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | pH | 3 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Nitrite | 1 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Specific Gravity | 3 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Erythrocytes | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Urobilinogen | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Urobilinogen | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | pH | 2 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Specific Gravity | 2 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Bilirubin | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Erythrocytes | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Nitrite | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Leukocytes | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Urobilinogen | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 1 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Erythrocytes | 1 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Leukocytes | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Nitrite | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Specific Gravity | 4 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Bilirubin | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | pH | 5 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Erythrocytes | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Bilirubin | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | pH | 4 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Leukocytes | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Urobilinogen | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Nitrite | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Specific Gravity | 5 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Bilirubin | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Leukocytes | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Nitrite | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | pH | 6 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Specific Gravity | 6 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Urobilinogen | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Erythrocytes | 2 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Leukocytes | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Nitrite | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Urobilinogen | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Specific Gravity | 5 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Bilirubin | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 1 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Erythrocytes | 1 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | pH | 8 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Bilirubin | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 1 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Nitrite | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Specific Gravity | 6 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | pH | 5 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Erythrocytes | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Leukocytes | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 2 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Urobilinogen | 0 Participants |
Primary
Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline
Blood samples were collected for the analysis of CD4+ T Cell Counts. The CD4+ T Cell Counts were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE). Grade 0: Above 0.5\*10\^9 cells/Liter (L), Grade 1: \<0.5 to 0.2\*10\^9 cells/L, Grade 2: \<0.2 to 0.05\*10\^9 cells/L, Grade 3: Below 0.05\*10\^9 cells/L. Baseline was defined as the latest pre-dose assessment. An increase was defined as an increase in grade relative to Baseline grade. Any worst-case post Baseline increase to Grade 1, Grade 2 and Grade 3 are presented.
Time frame: Baseline (Day 1) and up to 85 days
Population: Safety Population included all participants who received study intervention. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 4 Participants |
| Placebo | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 1 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 1 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 3 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 5 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 4 Participants |
Primary
Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline
Blood samples were collected for the analysis of Creatinine. Creatinine was graded according to the NCI-CTCAE. Grade 0: \<1.5\* Baseline, or increase from Baseline \<26 micromoles per liter (umol/L), Grade 1: 1.5 to 1.9\* Baseline, or increase from Baseline \>=26 umol/L, Grade 2: 2.0 to 2.9\* Baseline, Grade 3: \>=3.0\* Baseline, or \>=354 umol/L. Baseline was defined as the latest pre-dose assessment. An increase was defined as an increase in grade relative to Baseline grade. Any worst-case post Baseline increase to Grade 1, Grade 2 and Grade 3 are presented.
Time frame: Baseline (Day 1) and up to 85 days
Population: Safety Population included all participants who received study intervention. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 1 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 1 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 2 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Increase to Grade 3 | 0 Participants |
Primary
Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT corrected interval. Abnormal findings were categorized as clinically significant (CS) and 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Time frame: Up to 85 days
Population: Safety Population included all participants who received study intervention. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | NOT CLINICALLY SIGNIFICANT | 12 Participants |
| Placebo | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | CLINICALLY SIGNIFICANT | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | CLINICALLY SIGNIFICANT | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | NOT CLINICALLY SIGNIFICANT | 1 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | NOT CLINICALLY SIGNIFICANT | 2 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | CLINICALLY SIGNIFICANT | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | CLINICALLY SIGNIFICANT | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | NOT CLINICALLY SIGNIFICANT | 6 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | CLINICALLY SIGNIFICANT | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | NOT CLINICALLY SIGNIFICANT | 4 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | CLINICALLY SIGNIFICANT | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | NOT CLINICALLY SIGNIFICANT | 6 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | CLINICALLY SIGNIFICANT | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | NOT CLINICALLY SIGNIFICANT | 7 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | NOT CLINICALLY SIGNIFICANT | 5 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | CLINICALLY SIGNIFICANT | 0 Participants |
Secondary
Area Under the Concentration-time Curve From Time Zero to Time t (AUC[0 to t]) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve From Time Zero to Time t (AUC[0 to t]) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 65.81 Hours*micrograms per milliliter(h*ug/mL) | Geometric Coefficient of Variation 75.5 |
| GSK3888130B Dose Level 1 IV | Area Under the Concentration-time Curve From Time Zero to Time t (AUC[0 to t]) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 1837.01 Hours*micrograms per milliliter(h*ug/mL) | Geometric Coefficient of Variation 48.86 |
| GSK3888130B Dose Level 2 IV | Area Under the Concentration-time Curve From Time Zero to Time t (AUC[0 to t]) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 13524.34 Hours*micrograms per milliliter(h*ug/mL) | Geometric Coefficient of Variation 16.29 |
Secondary
AUC(0 to t) for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC(0 to t) for Dose Levels 3 and 5 Subcutaneous Administration | 3550.71 h*ug/mL | Geometric Coefficient of Variation 38.63 |
| GSK3888130B Dose Level 1 IV | AUC(0 to t) for Dose Levels 3 and 5 Subcutaneous Administration | 35669.70 h*ug/mL | Geometric Coefficient of Variation 25.35 |
Secondary
AUC(0 to t) for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC(0 to t) for Dose Levels 6 and 7 Intravenous Administration | 153885.4 h*ug/mL | Geometric Coefficient of Variation 12.54 |
| GSK3888130B Dose Level 1 IV | AUC(0 to t) for Dose Levels 6 and 7 Intravenous Administration | 387454.3 h*ug/mL | Geometric Coefficient of Variation 24.96 |
Secondary
Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 21.501 Milliliter per hour (mL/h) | Geometric Coefficient of Variation 38.138 |
| GSK3888130B Dose Level 1 IV | Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 4.240 Milliliter per hour (mL/h) | Geometric Coefficient of Variation 52.782 |
| GSK3888130B Dose Level 2 IV | Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 6.542 Milliliter per hour (mL/h) | Geometric Coefficient of Variation 22.034 |
Secondary
Clearance Factor (CL/F) of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clearance Factor (CL/F) of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | 9.149 mL/h | Geometric Coefficient of Variation 36.81 |
| GSK3888130B Dose Level 1 IV | Clearance Factor (CL/F) of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | 9.297 mL/h | Geometric Coefficient of Variation 27.211 |
Secondary
CL of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | CL of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | 5.920 mL/h | Geometric Coefficient of Variation 11.548 |
| GSK3888130B Dose Level 1 IV | CL of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | 6.860 mL/h | Geometric Coefficient of Variation 28.592 |
Secondary
Cmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | 3.4609 ug/mL | Geometric Coefficient of Variation 31.2624 |
| GSK3888130B Dose Level 1 IV | Cmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | 36.3795 ug/mL | Geometric Coefficient of Variation 24.923 |
Secondary
Cmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | 386.4759 ug/mL | Geometric Coefficient of Variation 29.7837 |
| GSK3888130B Dose Level 1 IV | Cmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | 907.7045 ug/mL | Geometric Coefficient of Variation 11.2907 |
Secondary
Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 123.73 Hour | Geometric Coefficient of Variation 35.44 |
| GSK3888130B Dose Level 1 IV | Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 633.05 Hour | Geometric Coefficient of Variation 32.53 |
| GSK3888130B Dose Level 2 IV | Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 627.11 Hour | Geometric Coefficient of Variation 17.66 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 0.9034 Micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 21.5707 |
| GSK3888130B Dose Level 1 IV | Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 4.8156 Micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 18.7069 |
| GSK3888130B Dose Level 2 IV | Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 35.6330 Micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 14.4965 |
Secondary
Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood
Blood samples were collected at indicated time points to measure Bcl-2 Expression in CD4+ T Cells as median fluorescence intensity (MdFI). Baseline was defined as the latest pre-dose assessment. MdFI values as a measure of Bcl-2 expression in CD4+ T cells was measured by flow cytometry. Placebo arms were combined as pre-specified in reporting and analysis plan.
Time frame: Baseline (Day 1) and Day 15
Population: Pharmacodynamic (PD) Population consisted of all participants in the Safety Population who had at least one post Baseline PD result. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) | 92427.0 Median fluorescence intensity |
| Placebo | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Day 15 | 88899.0 Median fluorescence intensity |
| GSK3888130B Dose Level 1 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) | 64576.0 Median fluorescence intensity |
| GSK3888130B Dose Level 1 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Day 15 | 79882.5 Median fluorescence intensity |
| GSK3888130B Dose Level 2 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) | 68096.0 Median fluorescence intensity |
| GSK3888130B Dose Level 2 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Day 15 | 75396.0 Median fluorescence intensity |
| GSK3888130B Dose Level 3 SC | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) | 92724.0 Median fluorescence intensity |
| GSK3888130B Dose Level 3 SC | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Day 15 | 62436.5 Median fluorescence intensity |
| GSK3888130B Dose Level 4 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) | 73182.5 Median fluorescence intensity |
| GSK3888130B Dose Level 4 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Day 15 | 52592.0 Median fluorescence intensity |
| GSK3888130B Dose Level 5 SC | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) | 93540.5 Median fluorescence intensity |
| GSK3888130B Dose Level 5 SC | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Day 15 | 55938.5 Median fluorescence intensity |
| GSK3888130B Dose Level 6 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Day 15 | 50715.0 Median fluorescence intensity |
| GSK3888130B Dose Level 6 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) | 90059.0 Median fluorescence intensity |
| GSK3888130B Dose Level 7 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Baseline (Day 1) | 101786.0 Median fluorescence intensity |
| GSK3888130B Dose Level 7 IV | Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood | Day 15 | 58098.5 Median fluorescence intensity |
Secondary
Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B
Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Baseline was defined as the latest pre-dose assessment.
Time frame: Baseline (Day 1), Day 15, Day 29, Day 57 and Day 85
Population: Safety Population included all participants who received study intervention. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points. Placebo arms were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 85 | 0 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 57 | 0 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 29 | 0 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1) | 0 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 15 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 85 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 57 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 15 | 0 Participants |
| GSK3888130B Dose Level 1 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 29 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 85 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 15 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 29 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 57 | 0 Participants |
| GSK3888130B Dose Level 2 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 85 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 57 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 29 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 15 | 0 Participants |
| GSK3888130B Dose Level 3 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 29 | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 85 | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1) | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 57 | 1 Participants |
| GSK3888130B Dose Level 4 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 15 | 1 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 57 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 15 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 29 | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 5 SC | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 85 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 85 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 29 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 15 | 0 Participants |
| GSK3888130B Dose Level 6 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 57 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 85 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Baseline (Day 1) | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 29 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 57 | 0 Participants |
| GSK3888130B Dose Level 7 IV | Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B | Day 15 | 0 Participants |
Secondary
Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood
Free IL-7 levels were derived from total IL-7 and total GSK3888130B concentrations (named as Derived Free IL-7) over time using a nonlinear mixed effects modelling approach. A target-mediated drug disposition model was used to fit the total IL-7 and total GSK3888130B assay concentration data to derive the free-IL-7 concentrations. Peak reduction relative to Baseline (Percent change) was calculated for each participant as; Peak reduction = (1 - minimum \[Free IL7/IL7 Baseline\])\*100. Baseline was defined as the latest pre-dose assessment.
Time frame: Baseline (Day 1) and up to 8 hours
Population: Pharmacodynamic (PD) Population consisted of all participants in the Safety Population who had at least one post Baseline PD result. Placebo arms were combined as pre-specified in reporting and analysis plan. Zeros reported reflect measured data derived during analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | 0.0 Percent Change | Standard Deviation 0 |
| GSK3888130B Dose Level 1 IV | Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | 95.8 Percent Change | Standard Deviation 1.5383 |
| GSK3888130B Dose Level 2 IV | Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | 99.1 Percent Change | Standard Deviation 0.2841 |
| GSK3888130B Dose Level 3 SC | Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | 90.3 Percent Change | Standard Deviation 4.2311 |
| GSK3888130B Dose Level 4 IV | Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | 99.9 Percent Change | Standard Deviation 0.0246 |
| GSK3888130B Dose Level 5 SC | Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | 98.6 Percent Change | Standard Deviation 0.8138 |
| GSK3888130B Dose Level 6 IV | Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | 100 Percent Change | Standard Deviation 0.0025 |
| GSK3888130B Dose Level 7 IV | Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood | 100 Percent Change | Standard Deviation 0.0004 |
Secondary
Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following intravenous administration. Pharmacokinetic (PK) Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: PK Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 29 | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 10 | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (Pre-dose) | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (12 Hours) | 758.1 Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (24 Hours) | 720.8 Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 57 | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (15 Minutes) | 363.2 Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (48 Hours) | 572.8 Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 21 | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (8 Hours) | 753.5 Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 6 | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 85 | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 15 | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 8 | NA Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (30 Minutes) | 893.1 Nanograms per milliliter (ng/mL) |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (4 Hours) | 761.4 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 10 | 1850.1 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 15 | 1539.6 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 21 | 1263.0 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 29 | 1027.3 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 57 | 625.4 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 85 | NA Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (4 Hours) | 4497.0 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (8 Hours) | 3964.2 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (Pre-dose) | NA Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (12 Hours) | 3599.9 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (24 Hours) | 3781.5 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (48 Hours) | 3184.0 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (15 Minutes) | 2155.9 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 6 | 2134.0 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 8 | 1862.5 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (30 Minutes) | 4717.5 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 85 | 1797.5 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (Pre-dose) | NA Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (15 Minutes) | 15901.1 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (30 Minutes) | 35633.0 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (4 Hours) | 32762.8 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (8 Hours) | 31180.8 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (12 Hours) | 29821.8 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (24 Hours) | 28096.6 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 1 (48 Hours) | 23358.3 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 6 | 15978.7 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 8 | 14071.9 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 10 | 12873.0 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 15 | 10293.7 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 21 | 8485.9 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 29 | 6904.9 Nanograms per milliliter (ng/mL) |
| GSK3888130B Dose Level 2 IV | Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | DAY 57 | 3545.2 Nanograms per milliliter (ng/mL) |
Secondary
Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following subcutaneous administration.
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (Pre-dose) | NA ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (4 Hours) | NA ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (8 Hours) | NA ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (12 Hours) | NA ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (24 Hours) | 1284.2 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (48 Hours) | 2297.0 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 6 | 3253.7 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 8 | 3327.1 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 10 | 3078.4 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 15 | 2814.4 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 21 | 2856.1 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 29 | 2266.1 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 57 | 1288.8 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 85 | NA ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 21 | 27433.3 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (Pre-dose) | NA ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 8 | 34801.7 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (4 Hours) | 2540.4 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 57 | 11567.5 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (8 Hours) | 5287.2 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 10 | 33654.8 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (12 Hours) | 8236.8 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 29 | 21108.5 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (24 Hours) | 14161.9 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 15 | 29870.9 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 1 (48 Hours) | 23239.0 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 85 | 5780.9 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | DAY 6 | 34612.8 ng/mL |
Secondary
Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration
Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following intravenous administration. Pharmacokinetic (PK) Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (Pre-dose) | NA ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 6 | 186043.0 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (8 Hours) | 333669.5 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 8 | 148716.7 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (1 Hour) | 365002.7 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 10 | 150354.6 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (12 Hours) | 312692.1 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 15 | 124163.7 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (30 Minutes) | 201271.5 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 21 | 108208.1 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (24 Hours) | 288550.5 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 29 | 88424.1 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 57 | 34733.0 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (4 Hours) | 334755.7 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 85 | 16634.1 ng/mL |
| Placebo | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (48 Hours) | 221884.4 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 85 | 53029.2 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (Pre-dose) | NA ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (30 Minutes) | 446824.2 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (1 Hour) | 887258.7 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (4 Hours) | 845654.2 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (8 Hours) | 839439.2 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (12 Hours) | 738220.9 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (24 Hours) | 744312.7 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 1 (48 Hours) | 595269.2 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 6 | 432475.7 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 8 | 362540.8 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 10 | 361427.9 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 15 | 311912.7 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 21 | 259786.4 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 57 | 100288.2 ng/mL |
| GSK3888130B Dose Level 1 IV | Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration | DAY 29 | 207998.2 ng/mL |
Secondary
t1/2 of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | t1/2 of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | 784.05 Hour | Geometric Coefficient of Variation 13.62 |
| GSK3888130B Dose Level 1 IV | t1/2 of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | 749.02 Hour | Geometric Coefficient of Variation 31.55 |
Secondary
t1/2 of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | t1/2 of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | 563.53 Hour | Geometric Coefficient of Variation 22.12 |
| GSK3888130B Dose Level 1 IV | t1/2 of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | 628.91 Hour | Geometric Coefficient of Variation 13.71 |
Secondary
Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 0.583 Hour |
| GSK3888130B Dose Level 1 IV | Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 0.550 Hour |
| GSK3888130B Dose Level 2 IV | Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration | 0.558 Hour |
Secondary
Tmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Tmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | 168.000 Hour |
| GSK3888130B Dose Level 1 IV | Tmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration | 143.475 Hour |
Secondary
Tmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Population: Pharmacokinetic Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Tmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | 1.083 Hour |
| GSK3888130B Dose Level 1 IV | Tmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration | 2.533 Hour |