A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (PD) of GSK3888130B in Healthy Participants

A Randomized, Double-Blind, Placebo Controlled, Single Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK3888130B in Healthy Participants Aged 18-55 Inclusive

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Colitis, Ulcerative
• Intervention / Treatment: Drug: Placebo; Drug: GSK3888130B

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 2GG
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Participants receiving GSK3888130B at dose level 1	Drug: GSK3888130B; GSK3888130B will be administered.
Placebo Comparator: Cohort 1: Participants receiving placebo	Drug: Placebo; Placebo will be administered.
Experimental: Cohort 2: Participants receiving GSK3888130B at dose level 2	Drug: GSK3888130B; GSK3888130B will be administered.
Placebo Comparator: Cohort 2: Participants receiving placebo	Drug: Placebo; Placebo will be administered.
Experimental: Cohort 3: Participants receiving GSK3888130B at dose level 3	Drug: GSK3888130B; GSK3888130B will be administered.
Placebo Comparator: Cohort 3: Participants receiving placebo	Drug: Placebo; Placebo will be administered.
Experimental: Cohort 4: Participants receiving GSK3888130B at dose level 4	Drug: GSK3888130B; GSK3888130B will be administered.
Placebo Comparator: Cohort 4: Participants receiving placebo	Drug: Placebo; Placebo will be administered.
Experimental: Cohort 5: Participants receiving GSK3888130B at dose level 5	Drug: GSK3888130B; GSK3888130B will be administered.
Placebo Comparator: Cohort 5: Participants receiving placebo	Drug: Placebo; Placebo will be administered.
Experimental: Cohort 6: Participants receiving GSK3888130B at dose level 6	Drug: GSK3888130B; GSK3888130B will be administered.
Placebo Comparator: Cohort 6: Participants receiving placebo	Drug: Placebo; Placebo will be administered.
Experimental: Cohort 7: Participants receiving GSK3888130B at dose level 7	Drug: GSK3888130B; GSK3888130B will be administered.
Placebo Comparator: Cohort 7: Participants receiving placebo	Drug: Placebo; Placebo will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 160 days
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.	Up to 85 days
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.	Baseline (Day 1) and up to 85 days
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.	Baseline (Day 1) and up to 85 days
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.	Up to 85 days
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.	Baseline (Day 1) and up to 85 days
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.	Up to 85 days
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.	Baseline (Day 1), Day 15 and Day 85
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.	Baseline (Day 1), Day 15 and Day 85
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.	Up to 85 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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).	Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
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.	Baseline (Day 1), Day 15, Day 29, Day 57 and Day 85
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.	Baseline (Day 1) and up to 8 hours
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.	Baseline (Day 1) and Day 15

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): October 12, 2023
• Study Completion (Actual): October 12, 2023

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Single Dose Escalation; Double-blind; Anti-Drug Antibodies; GSK3888130B; Pharmacodynamics
• Additional Relevant MeSH Terms: Nervous System Diseases; Intestinal Diseases; Autoimmune Diseases; Immune System Diseases; Digestive System Diseases; Gastrointestinal Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Multiple Sclerosis; Colitis, Ulcerative
• Other Study ID Numbers: 213960; 2021-002063-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No