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

NCT05174013 | Completed Phase 1 Results

• 1 other identifier: 212979
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Pain

Keywords

Pharmacokinetics; Safety; Tolerability; GSK3858279; Placebo; Caucasian; Chinese; Japanese

Outcome Measures

Primary Outcomes (23)

• Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAE's) And Withdrawals Due to AE's

  An AE is defined as 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. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169.

  Up to 169 days

• Change From Baseline in Hematology Parameter of Platelet Count

  Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Hematology Parameter of Hemoglobin

  Blood samples were collected for the assessment of change from baseline in hematology parameters Hemoglobin. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Hematology Parameter of Hematocrit

  Blood samples were collected for the assessment of change from baseline in hematology parameters Hematocrit. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in White Blood Cell (Wbc) Count With Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils

  Blood samples were collected for the assessment of hematology parameters including (WBC) count with differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP)

  Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Clinical Chemistry Parameter of Total Protein

  Blood samples were collected for the assessment of clinical chemistry parameters including total Protein. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin

  Blood samples were collected for the assessment of clinical chemistry parameters including Total bilirubin. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Clinical Chemistry Parameter of Direct Bilirubin, Creatinine

  Blood samples were collected for the assessment of clinical chemistry parameters including Direct bilirubin, Creatinine. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Clinical Chemistry Parameter of Urea, Glucose, Potassium, Sodium

  Blood samples were collected for the assessment of clinical chemistry parameters including Urea, Glucose, Potassium, Sodium. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Number of Participants With Change From Baseline in Urinalysis Parameter: Urine Specific Gravity (Ratio of Urine Density to Water Density)

  Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.

  Baseline and Day 169

• Number of Participants With Change From Baseline in Urinalysis Parameter: Urine Potential of Hydrogen (pH)

  Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.

  Baseline and Day 169

• Number of Participants With Abnormal Urinalysis Results by Dipstick Method

  The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as increase to trace, increase to 1+ (low concentrations present), increase to 2+ (moderate concentrations present) and increase to 3+ (high concentrations present) indicating proportional concentrations in the urine sample. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for worst-case post-Baseline relative to Baseline is presented.

  Baseline and Day 169

• Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

  The vital sign followed in this analysis was both systolic and diastolic blood pressure, expressed as millimetre of mercury. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Vital Signs: Pulse Rate

  The vital signs followed in this analysis was pulse rate, expressed as beats per minute. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Vital Signs: Body Temperature

  The vital sign followed in this analysis was body temperature, expressed as degree Celsius. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Vital Signs: Respiratory Rate

  The vital signs followed in this analysis was respiratory rate, expressed as Breaths per minute. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

  Baseline and Day 169

• Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF) Interval

  Twelve-lead ECG were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Baseline was defined as the average of the triplicate pre-dose assessments on Day 1 of Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

  Baseline and Day 169

• Area Under the Plasma Concentration-Time Curve From Time Zero to 56 Days AUC (0-56)] of GSK3858279

  Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters. PK parameter population consist of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. This population was used in the assessment and characterization of PK parameters.

  Predose, 6 Hour (h), 12 h, 24 h, 36 h, 48 h (post dose till Day 3), Day 8, 15, 22, 29, 43 and 57

• AUC From Time Zero to the Last Measurable Concentration (0-t) Post-Dose of GSK3858279

  Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters. PK parameter population consist of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. This population was used in the assessment and characterization of PK parameters.

  Predose, 6 Hour (h), 12 h, 24 h, 36 h, 48 h (post dose till Day 3), Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 155 and 169 Days

• Time of Occurrence of Last Quantifiable Concentration (Tlast) of GSK3858279

  Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

  Predose, 6 Hour (h), 12 h, 24 h, 36 h, 48 h (post dose till Day 3), Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 155 and 169 Days

• Maximum Observed Concentration (Cmax) of GSK3858279

  Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

  Predose, 6 Hour (h), 12 h, 24 h, 36 h, 48 h (post dose till Day 3), Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 155 and 169 Days

• Time of Occurrence of Cmax (Tmax) of GSK3858279

  Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

  Predose, 6 Hour (h), 12 h, 24 h, 36 h, 48 h (post dose till Day 3), Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 155 and 169 Days

Secondary Outcomes (7)

• Percentage Change From Baseline in Free CCL17

  Baseline (Day 1) and at Days 7, 14, 28 and 56 Post dose

• Cmax of Total CCL17 in Serum Following GSK3858279

  Baseline (Day 1) and at Days 7, 14, 28 and 56 Post dose

• Tmax of Total CCL17 in Serum Following GSK3858279

  Baseline (Day 1) and at Days 7, 14, 28 and 56 Post dose

• Maximum Fold Change in Total CCL17 in Serum Following GSK3858279 Administration

  Baseline (Day 1) and Days 56 Post dose

• Fold Increase in Total CCL17 in Serum Following GSK3858279 Administration

  Baseline (Day 1) and at Days 7, 14, 28 and 56 Post dose

Study Arms (6)

GSK3858279 Caucasian

EXPERIMENTAL

Participants received 240 milligrams (mg) of GSK3858279 administered as separate subcutaneous (SC) injection to healthy Caucasian participants.

Drug: GSK3858279

GSK3858279 Chinese

EXPERIMENTAL

Participants received 240 mg of GSK3858279 administered as separate SC injection to healthy Chinese participants.

Drug: GSK3858279

GSK3858279 Japanese

EXPERIMENTAL

Participants received 240 mg of GSK3858279 administered as separate SC injection to healthy Japanese participants.

Drug: GSK3858279

Caucasian Placebo

PLACEBO COMPARATOR

Participants received single dose of Placebo administered as separate SC injection to healthy Caucasian participants.

Drug: Placebo

Chinese Placebo

PLACEBO COMPARATOR

Participants received Single dose of Placebo administered as separate SC injection to healthy Chinese participants.

Drug: Placebo

Japanese Placebo

PLACEBO COMPARATOR

Participants received Single dose of Placebo administered as separate SC injection to healthy Japanese participants.

Drug: Placebo

Interventions

GSK3858279 DRUG

GSK3858279 will be administered

GSK3858279 Caucasian; GSK3858279 Chinese; GSK3858279 Japanese

Placebo DRUG

Placebo will be administered

Caucasian Placebo; Chinese Placebo; Japanese Placebo

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Herston Queensland, Queensland, 4006, Australia

Location

GSK Investigational Site

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double blind study
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: December 30, 2021
• Study Start: February 14, 2022
• Primary Completion: February 10, 2023
• Study Completion: April 17, 2023
• Last Updated: May 15, 2025
• Results First Posted: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

AU (2)