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

Phase 1CompletedNCT05131971

GlaxoSmithKline54 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Multiple Sclerosis Colitis, Ulcerative

Interventions

GSK3888130BDRUG

GSK3888130B will be administered.

PlaceboDRUG

Placebo will be administered.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

GSK Investigational Site

Cambridge, United Kingdom

Outcomes

Primary Outcomes

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

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

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

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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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

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

Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV 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

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