Clinical trial NCT04138043: Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of GSK2330811 in Healthy Japanese Participants
Official title: A Phase 1, Randomised, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Subcutaneous Doses of GSK2330811 in Healthy Japanese Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: GSK2330811
Healthy participants
Japanese
Pharmacokinetics
Safety
Subcutaneous dose
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-10-24
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a parallel group study. Participants will be randomized to receive either GSK2330811 (450 mg) or placebo in an approximate ratio of 7:3.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
* Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECGs.
* A participant with a clinical abnormality or laboratory parameters outside the reference range for the healthy population being studied that is not specifically listed in the inclusion or exclusion criteria may be included if the investigator and sponsor medical monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or interpretation.
* Participants with body weight \>=45 kilogram (kg) and body mass index (BMI) within the range 18.5-29.9 kg per square meter.
* Male participants.
* Participants 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 with Japanese ancestry, defined as having been born in Japan, being descendants of four ethnic Japanese grandparents and two ethnic Japanese parents, holding a Japanese passport or identity papers, and being able to speak Japanese. Participants should have lived outside Japan for less than 10 years at the time of screening.

Exclusion Criteria:

* Participants with sensitivity to any of the study treatments or components there of (including humanized monoclonal antibodies) or history of severe post treatment hypersensitivity reactions including erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis and exfoliative dermatitis.
* Participants with any other history of significant allergy that in the opinion of the investigator contraindicates their participation in this study.
* Participants with an active infection or a history of serious infections as follows: Use of antimicrobials (antibacterials, antivirals, antifungals or antiparasitic agents) for an infection within 30 days prior to Day 1. Topical treatments may be allowed at the Investigator's discretion (in consultation with the Medical Monitor); A history of opportunistic or recurrent infections, as determined by the investigator; Currently active or unresolved infection (participants with 'trivial' infections such as tinea pedis may be eligible at the discretion of the investigator); Symptomatic herpes zoster within 3 months prior to screening; History of tuberculosis (TB) (active or latent) irrespective of treatment status; and a positive diagnostic TB test at screening (defined as a positive QuantiFERON test).
* Participants with any planned major surgical procedure during the study.
* Participants with a history of hematological disease, for example (but not limited to): significant anemia, platelet disorders including drug-induced thrombocytopenia or primary immune thrombocytopenia and coagulation disorders including von Willebrand's disease.
* Participants with a history of carcinoma in situ and malignant disease, with the exception of adequately treated non-metastatic basal or squamous cell cancer of the skin that has been fully treated and shows no evidence of recurrence after 3 years.
* Participants with QTc \>450 millisecond (msec) at screening.
* Participants with use of prescription or non-prescription drugs (including recreational drugs and herbal medications) within 7 days or 5 half-lives (whichever is longer) prior to Day 1 unless in the opinion of the investigator (in consultation with the sponsor medical monitor) the medication will not interfere with the study or compromise participant safety. Paracetamol at doses of \<=4 grams per day, and occasional use of non-steroidal anti-inflammatory drugs (NSAIDs) at licensed doses, are permitted.
* Participants who received live vaccination within 4 weeks prior to Day 1, or any plan to receive a live vaccination during the study (up to and including to the last follow-up visit).
* Participation in a clinical trial and has received an investigational medicine product (IMP) within the following time period prior to Day 1: 3 months, 5 half-lives, or twice the duration of the biological effect of the IMP (whichever is longer).
* Participants with exposure to more than 4 new chemical entities within 12 months prior to Day 1.
* Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
* Participants with platelet count or hemoglobin below the normal range at any time during screening.
* Participants with alanine aminotransaminase (ALT) \>1.5 times upper limit of normal (ULN) at any time during screening.
* Participants with bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent) at any time during screening.
* Participants with presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), or positive hepatitis C virus (HCV) antibody result at screening. Participants with positive HCV antibody due to prior resolved disease can be enrolled only if a confirmatory negative HCV Ribonucleic acid (RNA) test is obtained.
* Participants with positive human immunodeficiency virus (HIV) antibody test at screening.
* Participants with positive pre-study drug or alcohol screen.
* Participants with history of regular alcohol consumption within 6 months of the screening visit in excess of an average weekly intake of \>21 units. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Participants planning to travel to regions of high endemic infection, as determined by the investigator, for the duration of the study.
* Participants with unstable lifestyle factors, to the extent that in the opinion of the investigator they would interfere with the ability of a participant to complete the study.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 126
measure: Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
timeFrame: Baseline (Pre-dose, Day 1) and up to Day 126
measure: Change From Baseline in Body Temperature
timeFrame: 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
measure: Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to Day 126
measure: Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters
timeFrame: Up to Day 126
measure: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters
timeFrame: Baseline (Pre-dose, Day 1) and up to Day 126
measure: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline
timeFrame: Baseline (Pre-dose, Day 1) and up to Day 126
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) for GSK2330811
timeFrame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Area Under the Plasma Concentration Time-curve From Time Zero to Infinity (AUC[0-infinity]) for GSK2330811
timeFrame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2330811
timeFrame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Apparent Systemic Clearance (CL/F) for GSK2330811
timeFrame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Time to Cmax (Tmax) for GSK2330811
timeFrame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Terminal Half-life (t1/2) for GSK2330811
timeFrame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Apparent Volume of Distribution at Steady State (Vss/F) for GSK2330811
timeFrame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Number of Participants With Positive Anti-GSK2330811 Antibodies
timeFrame: Up to Day 126
measure: Platelet Count Nadir for GSK2330811
timeFrame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Time to Platelet Count Nadir for GSK2330811
timeFrame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Hemoglobin Nadir for GSK2330811
timeFrame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
measure: Time to Hemoglobin Nadir for GSK2330811
timeFrame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: