Safety, Tolerability, Pharmacokinetics and Target Engagement of GSK3858279 in Healthy Caucasian, Chinese and Japanese Participants

A Randomised, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, Target Engagement and Immunogenicity of a Single Subcutaneous Dose of GSK3858279 Administered to Healthy Caucasian, Chinese and Japanese Participants

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), target engagement (TE) and immunogenicity of GSK3858279 when administered to healthy Caucasian, Chinese and Japanese participants.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Placebo; Drug: GSK3858279

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • GSK Investigational Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants between 20 and 65 years of age inclusive, at the time of signing the informed consent.
• Volunteers who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Participant capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Participants who have evidence of completed vaccination for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an approved vaccine.
• Body weight within the range 45 - 100 killogram (kg) and body mass index (BMI) within the range 18-29.9 kg per meter square (/m2) (inclusive).
• Japanese participants are eligible based on meeting all of the following:
• Participants born in Japan
• Descendants of four ethnic Japanese grandparents and two ethnic Japanese parents.
• Have lived outside Japan for less than (<) 10 years at the time of screening
• Chinese participants are eligible based on meeting all of the following
• Participants born in mainland China, Hong Kong or Taiwan
• Descendants of four Chinese grandparents and two Chinese parents
• Have lived outside China, Hong Kong or Taiwan for <10 years at the time of screening
• Caucasian participants are eligible based on meeting the following
• Declaration of familial Caucasian/European ancestry (having 2 parents of Caucasian/European ancestry and 4 grandparents of Caucasian/European ancestry)
• Male or female participant
• Male participants are eligible to participate if they agree to the following for at least 28 weeks after the dose of study intervention: Refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR must agree to use contraception/barrier as detailed below: agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
• A female participant is eligible to participate if she is of non-reproductive potential.
• Capable of giving signed informed consent.

Exclusion Criteria:

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
• Personal or family history of cardiomyopathy.
• Abnormal blood pressure at screening as determined by the investigator.
• History of symptomatic herpes zoster.
• Evidence of active or latent tuberculosis (TB) as documented by medical history, examination, and TB testing with a positive (not indeterminate) QuantiFERON test.
• Significant allergies to humanized monoclonal antibodies as per principal investigator's and GSK medical monitor's judgements.
• History or evidence of clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
• History of lymphoma, leukaemia, or any malignancy within the last 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.

ALT greater than (>)1.5 times upper limit of normal (ULN) .

• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Corrected QT (QTc) >450 milliseconds (msec).
• History of Stevens Johnson Syndrome.
• Known immunodeficiency.
• Participants with a chronic infection (for example [e.g.], osteomyelitis), who have been receiving treatment within three months prior to dosing or individuals with an active infection.
• Previous or current history of bleeding diathesis, excessive bleeding or coagulation disorders.
• History of significant medical illness in the opinion of the investigator would interfere with the study procedures and / or assessments.
• Intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing until final follow-up visit.
• Live vaccine(s) or plans to receive such vaccines within 1 month of screening until final follow-up visit.
• Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
• Treatment with antiplatelet or anticoagulant agents within 7 days of dosing.
• Major surgery (as per investigator's judgement) within 3 months prior to dosing.
• Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 3 months.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Current enrolment or past participation in any other clinical study involving an investigational drug intervention within the last 3 months or 5 half-lives (whichever is longer) of signing the ICF.
• Presence of Hepatitis B surface antigen (HBsAg) at screening.
• Presence of the Hepatitis B core antibody (HBcAb) at screening.
• Positive Hepatitis C antibody test result at screening.
• Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
• Abnormal clinically significant echocardiogram at screening, as assessed by the investigator.
• Cardiac troponin or N-terminal pro B-type natriuretic peptide (NT-proBNP) levels out of normal range at screening.
• Positive pre-study drug/alcohol screen.
• Positive human immunodeficiency virus (HIV) antibody test.
• Positive coronavirus disease 2019 (COVID-19): SARS-CoV2 polymerase chain reaction (PCR) or lateral flow test of a combined throat and nasopharyngeal swab or nasal swab only.
• Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >14 units for males and >14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Regular use of known drugs of abuse.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Participants receiving placebo	Drug: Placebo; Placebo will be administered
Experimental: Participants receiving GSK3858279	Drug: GSK3858279; GSK3858279 will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events (AEs), serious AE(SAE) and withdrawals due to AEs	Up to 173 days
Change from Baseline in hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and platelet count (Giga cells per liter)	Baseline and up to 173 days
Change from Baseline in hematology Parameter: Red blood cell count (RBC) (Trillion cells per liter)	Baseline and up to 173 days
Change from Baseline in hematology Parameter: Hemoglobin (Grams per Liter)	Baseline and up to 173 days
Change from Baseline in hematology Parameter: Hematocrit (Proportion of red blood cells in blood	Baseline and up to 173 days
Change from Baseline in hematology Parameter: RBC indices (Millions per cubic millimeter)	Baseline and up to 173 days
Change from Baseline in hematology Parameter: Mean Corpuscular Volume (MCV) (Femtoliters)	Baseline and up to 173 days
Change from Baseline in hematology Parameter: Mean corpuscular hemoglobin (MCH) (picograms)	Baseline and up to 173 days
Change from Baseline in hematology Parameter: Reticulocytes (Percentage of reticulocytes)	Baseline and up to 173 days
Change from Baseline in clinical chemistry parameters: Alanine Amino Transferase (ALT),Alkaline Phosphatase (ALP),Aspartate Amino Transferase (AST) (International units per Liter)	Baseline and up to 173 days
Change from Baseline in clinical chemistry parameters: Calcium, glucose (non-fasting), potassium, sodium,urea (Millimoles per Liter)	Baseline and up to 173 days
Change from Baseline in clinical chemistry parameters: Creatinine, direct bilirubin, total bilirubin (Micromoles per liter)	Baseline and up to 173 days
Change from Baseline in clinical chemistry parameters: Total protein (Grams per liter)	Baseline and up to 173 days
Change from Baseline in Urinalysis parameter: Urine Specific Gravity (Ratio of urine density to water density)	Baseline and up to 173 days
Change from Baseline in Urinalysis parameter: Urine Potential of Hydrogen (pH)	Baseline and up to 173 days
Number of Participants With Abnormal Urinalysis Results by Dipstick Method	Up to 173 days
Change from Baseline in vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (Millimeters of mercury)	Baseline and up to 173 days
Change from Baseline in vital sign : Pulse rate (Beats per minute)	Baseline and up to 173 days
Change from Baseline in vital signs: Body temperature ( Degrees Celsius)	Baseline and up to 173 days
Change from Baseline in vital signs: Respiratory rate (Breaths per minute)	Baseline and up to 173 days
Change from Baseline in vital signs:Heart Rate (Beats per minute)	Baseline and up to 173 days
Change from Baseline in Electrocardiogram (ECG) parameters: PR Interval, QRS Duration, QT Interval and QT interval corrected for heart rate according Fridericia's formula (QTcF) Interval (Milliseconds)	Baseline and up to 173 days
Area Under the plasma Concentration-Time Curve from Time zero to 56 Days [AUC(0-56)] of GSK3858279	Upto 56 days
AUC from Time zero to the last measurable concentration (0-t) post-dose of GSK3858279	Up to 173 days
Time of occurrence of last quantifiable concentration (tlast) of GSK3858279	Up to 173 days
Maximum observed concentration (Cmax) of GSK3858279	Up to 173 days
Time of occurrence of Cmax (tmax) of GSK3858279	Up to 173 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent change from Baseline in free CCL17	Baseline and at Days 7, 14, 28 and 56
Cmax of total CCL17 in serum following GSK3858279	Baseline and at Days 7, 14, 28 and 56
tmax of total CCL17 in serum following GSK3858279	Baseline and at Days 7, 14, 28 and 56
Number of participants with indicated fold increase in total CCL17 in serum following GSK3858279	Baseline and at Days 7, 14, 28 and 56
Number of participants with pre-existing anti-drug antibodies (ADAs)	Up to 173 days
Number of participants with treatment-emergent ADAs over time	Up to 173 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): June 2, 2023
• Study Completion (Actual): June 2, 2023

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): December 30, 2021

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Chinese; Pharmacokinetics; Japanese; Tolerability; Placebo; Caucasian; GSK3858279
• Other Study ID Numbers: 212979

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