Clinical trial NCT05131971: A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (PD) of GSK3888130B in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis
Colitis, Ulcerative
Keywords: Anti-Drug Antibodies
Double-blind
GSK3888130B
Pharmacodynamics
Pharmacokinetics
Single Dose Escalation
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-11-23
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Participants will be randomized to receive either GSK3888130B or placebo in single ascending dose cohorts.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 160 days
measure: Number of Participants With Clinically Significant Changes in Hematology Results
timeFrame: Up to 85 days
measure: Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline
timeFrame: Baseline (Day 1) and up to 85 days
measure: Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline
timeFrame: Baseline (Day 1) and up to 85 days
measure: Number of Participants With Clinically Significant Changes in Clinical Chemistry Results
timeFrame: Up to 85 days
measure: Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline
timeFrame: Baseline (Day 1) and up to 85 days
measure: Number of Participants With Clinically Significant Changes in Vital Sign Results
timeFrame: Up to 85 days
measure: Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA
timeFrame: Baseline (Day 1), Day 15 and Day 85
measure: Number of Participants With Positive Epstein-Barr Virus (EBV) DNA
timeFrame: Baseline (Day 1), Day 15 and Day 85
measure: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to 85 days
Secondary outcomes:
measure: Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
timeFrame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
timeFrame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration
timeFrame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: 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
timeFrame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: AUC(0 to t) for Dose Levels 3 and 5 Subcutaneous Administration
timeFrame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: AUC(0 to t) for Dose Levels 6 and 7 Intravenous Administration
timeFrame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
timeFrame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Cmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
timeFrame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Cmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
timeFrame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
timeFrame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Tmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
timeFrame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Tmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
timeFrame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
timeFrame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: t1/2 of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
timeFrame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: t1/2 of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
timeFrame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
timeFrame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Clearance Factor (CL/F) of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
timeFrame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: CL of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
timeFrame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
measure: Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B
timeFrame: Baseline (Day 1), Day 15, Day 29, Day 57 and Day 85
measure: Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood
timeFrame: Baseline (Day 1) and up to 8 hours
measure: Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood
timeFrame: Baseline (Day 1) and Day 15
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: