NCT04138043

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of GSK2330811 in Healthy Japanese Participants

Completed Phase 1 Results posted Last updated 24 May 2021

What this trial tests

Phase 1 trial testing Placebo in Healthy Volunteers in 9 participants. Completed in 28 May 2020.

Timeline

5 December 2019

Primary endpoint
28 May 2020

28 May 2020

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	9
Start date	5 December 2019
Primary completion	28 May 2020
Estimated completion	28 May 2020
Sites	1 location across United Kingdom

Drugs / interventions tested

• Placebo
• GSK2330811 — full drug profile →

Conditions studied

• Healthy Volunteers — all drugs for Healthy Volunteers →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 65, male only, with Healthy Volunteers. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · Up to Day 126

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. A SAE is defined as any untoward medical occurrence 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, congenital anomaly/birth defect, any other situation according to medical or scientific judgment. Safety Population consisted of all randomized participant

AEs

Group	Value	95% CI
Placebo	2
GSK2330811 450 mg	6

SAEs

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Primary · Baseline (Pre-dose, Day 1) and up to Day 126

Vital signs were measured in semi-supine position after 5 minutes of rest and included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Participants were counted in the worst case category that their value changed to low, within range or high, unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "Within Range or No Change" category. Participants were counted twice if values changed 'To Low' and 'To High', so the percentages were not added up to

SBP, To low

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

SBP, To Within Range or No Change

Group	Value	95% CI
Placebo	2
GSK2330811 450 mg	7

SBP, To high

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

DBP, To low

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

DBP, To Within Range or No Change

Group	Value	95% CI
Placebo	2
GSK2330811 450 mg	7

DBP, To high

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

HR, To low

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

HR, To Within Range or No Change

Group	Value	95% CI
Placebo	2
GSK2330811 450 mg	7

Change From Baseline in Body Temperature Primary · Baseline (Pre-dose, Day 1), Day 1: 1, 4, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

Body temperature was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Day 1: 1 hour, n=2,7

Group	Value	95% CI
Placebo	0.15	± 0.212
GSK2330811 450 mg	0.06	± 0.237

Day 1: 4 hour, n=2,7

Group	Value	95% CI
Placebo	0.40	± 0.283
GSK2330811 450 mg	0.07	± 0.287

Day 1: 8 hour, n=2,7

Group	Value	95% CI
Placebo	0.45	± 0.071
GSK2330811 450 mg	0.40	± 0.346

Day 2: n=2,7

Group	Value	95% CI
Placebo	-0.15	± 0.919
GSK2330811 450 mg	-0.03	± 0.486

Day 3: n=2,7

Group	Value	95% CI
Placebo	-0.30	± 0.283
GSK2330811 450 mg	-0.34	± 0.336

Day 5: n=2,7

Group	Value	95% CI
Placebo	0.20	± 0.424
GSK2330811 450 mg	-0.06	± 0.800

Day 7: n=2,7

Group	Value	95% CI
Placebo	-0.30	± 0.566
GSK2330811 450 mg	0.09	± 0.521

Day 10: n=2,7

Group	Value	95% CI
Placebo	-0.10	± 0.283
GSK2330811 450 mg	-0.10	± 0.862

Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings Primary · Up to Day 126

12-lead ECGs were recorded in semi-supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal laboratory findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Abnormal - not clinically significant

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	1

Abnormal - clinically significant

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters Primary · Up to Day 126

Blood samples were collected for the analysis of clinical chemistry parameters. Clinical chemistry parameters were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Clinical chemistry parameters included: total bilirubin, calcium, creatinine and triglycerides.

Total Bilirubin, Grade 1

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	1

Total Bilirubin, Grade 2

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Total Bilirubin, Grade 3

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Total Bilirubin, Grade 4

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Calcium, Grade 1

Group	Value	95% CI
Placebo	2
GSK2330811 450 mg	5

Calcium, Grade 2

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Calcium, Grade 3

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Calcium, Grade 4

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters Primary · Baseline (Pre-dose, Day 1) and up to Day 126

Blood samples were collected for the analysis of the following hematology parameters: hemoglobin (Hb), lymphocytes (Lympho), platelet count (PC), neutrophil count (Neutro) and White Blood Cell count (WBC). The laboratory parameters were graded according to NCI-CTCAE version 5.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severity. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. An increase was defined as an increase

Hb, Anemia, increase to Grade 1

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Hb, Anemia, increase to Grade 2

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Hb, Anemia, increase to Grade 3

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Hb, Anemia, increase to Grade 4

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Hb, Hb increased, increase to Grade 1

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Hb, Hb increased, increase to Grade 2

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Hb, Hb increased, increase to Grade 3

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Hb, Hb increased, increase to Grade 4

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline Primary · Baseline (Pre-dose, Day 1) and up to Day 126

Urine samples were collected for analysis of blood, glucose, ketones and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, protein, blood and ketones can be read as negative (-), trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Number of participants wi

Blood

Group	Value	95% CI
Placebo	1
GSK2330811 450 mg	1

Glucose

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	0

Ketones

Group	Value	95% CI
Placebo	0
GSK2330811 450 mg	1

Protein

Group	Value	95% CI
Placebo	1
GSK2330811 450 mg	2

Maximum Plasma Concentration (Cmax) for GSK2330811 Secondary · Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. Pharmacokinetic Population consisted of all participants in the Safety population who received at least one active dose of study treatment and had at least 1 non-missing PK assessment.

Group	Value	95% CI
GSK2330811 450 mg	63259.308	± 14.9290

Area Under the Plasma Concentration Time-curve From Time Zero to Infinity (AUC[0-infinity]) for GSK2330811 Secondary · Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

Group	Value	95% CI
GSK2330811 450 mg	45371065.201	± 22.1925

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2330811 Secondary · Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

Group	Value	95% CI
GSK2330811 450 mg	43157791.065	± 22.8839

Apparent Systemic Clearance (CL/F) for GSK2330811 Secondary · Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

Group	Value	95% CI
GSK2330811 450 mg	0.010	± 22.1925

Time to Cmax (Tmax) for GSK2330811 Secondary · Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

Group	Value	95% CI
GSK2330811 450 mg	143.380	94.82 – 216.25

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality, SAEs and non SAEs were collected up to Day 126. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/2 (0%)

Deaths: 0/2

GSK2330811 450 mg

Serious: 0/7 (0%)

Deaths: 0/7

Other adverse events (13 terms — click to expand)

Reaction	System	Placebo	GSK2330811 450 mg
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Arthropod bite	Injury, poisoning and procedural complications	—	—
Face injury	Injury, poisoning and procedural complications	—	—
Skin laceration	Injury, poisoning and procedural complications	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Mouth ulceration	Gastrointestinal disorders	—	—
Injection site bruising	General disorders	—	—
Injection site pain	General disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Oral herpes	Infections and infestations	—	—
Suspected COVID-19	Infections and infestations	—	—
Dermatitis	Skin and subcutaneous tissue disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—

Data from ClinicalTrials.gov NCT04138043 adverse events section.

Sponsor's own description

This is a randomized, double-blind (sponsor-open), placebo-controlled, single-center study involving Japanese participants. The purpose of the study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity after a single subcutaneous (SC) dose of GSK2330811 in healthy Japanese participants. GSK2330811 is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that binds and inhibits the action of Oncostatin M (OSM) and is being developed for the treatment of Crohn's disease (CD) and Systemic sclerosis (SSc). Participants will be randomized to receive either GSK2330811 (450 milligram \[mg\]) or placebo in an approximate ratio of 7:3.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Immunotherapy drug target identification using machine learning and patient-derived tumour explant validation.
   Augustine M, Nene NR, Fu H, Pinder CL, et al · · 2026 · PMID 42206145 · DOI 10.1038/s42256-026-01201-3