A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic of GSK1070806 After a Single Intravenous Dose in Healthy Male and Female Caucasian, Chinese and Japanese Participants Aged 18 to 65 Years of Age Inclusive

A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamic of a Single Intravenous Dose of GSK1070806 Administered to Healthy Male and Female Caucasian, Chinese and Japanese Participants Aged 18 to 65 Years of Age Inclusive

This study is divided into two parts:

Part A of the study is double blinded, randomized, placebo-controlled and aims to assess the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamic (PD) effect of a single intravenous (IV) infusion dose of GSK1070806 when administered to healthy participants of Japanese, Chinese and European/Caucasian ancestry.

Part B of the study is an open label single cohort arm to assess the safety, tolerability, PK and PD effect of a single IV bolus low dose of GSK1070806 in healthy participants of European/Caucasian ancestry.

Study Overview

• Status: Completed
• Conditions: Dermatitis, Atopic
• Intervention / Treatment: Drug: Placebo; Drug: GSK1070806

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring [12-lead Electrocardiogram (ECGs)]
• Between 18 and 65 years of age inclusive, at the time of signing the informed consent
• Body weight within the range 45 - 100 kilograms (kg) and body mass index (BMI) within the range 18-32 kilogram/meter square (kg/m^2) (inclusive)
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
• Is a woman of non-childbearing potential (WONCBP) OR
• Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective [with a failure rate of less than 1 percent (<1%) per year], with low user dependency
• Capable of giving signed informed consent
• Participants of Japanese ancestry are eligible based on meeting all of the following:
• Healthy male and female 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:
• Healthy male and female participants born in mainland China, Hong Kong, Macau or Taiwan
• Descendants of four ethnic Chinese grandparents and two ethnic Chinese parents
• Have lived outside mainland China, Hong Kong, Macau or Taiwan for less than 10 years at the time of screening
• Participants of Caucasian/European ancestry are eligible if they self-identify to be of Caucasian/European ancestry and have 2 parents of Caucasian/European ancestry and 4 grandparents of Caucasian/European ancestry

Exclusion Criteria:

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, immunological, metabolic, musculoskeletal 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
• Known varicella, herpes zoster, or other severe viral infection within 6 weeks of anticipated dosing on Day 1. Or history of recurrent herpes reactivation in the past 2 years
• Evidence of active or latent tuberculosis (TB) as documented by medical history, examination, and TB testing with a positive (not indeterminate) QuantiFERON test
• 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, anaphylaxis, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis)
• Lymphoma, leukemia, or any malignancy except for basal cell carcinomas of the skin that have been resected with no evidence of metastatic disease for 5 years
• Alanine transaminase (ALT) greater than (>) 1.5x upper limit of normal (ULN)
• Total bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or previous uncomplicated cholecystectomy more than 3 months ago)
• Corrected QT using Bazett's formula (QTcB) (Bazett) or Corrected QT using Fridericia's formula (QTcF) (Fridericia) interval >450 milli second (msec)
• History of Stevens Johnson Syndrome
• Known immunodeficiency
• Previous or current history of bleeding diathesis
• Intended use of over the counter or prescription medication including herbal medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or five half-lives (whichever is longer) prior to dosing until final follow-up visit
• Live vaccine(s) or plans to receive such vaccines within 2 months of dosing until final follow-up visit
• Participation in the study would result in loss of blood or blood products in excess of 500 milli liter (mL) within 3 months
• Current enrollment or past participation in any other clinical study involving an investigational study intervention or any other type of medical research within the last 30 days, 5 half-lives or twice the duration of the known pharmacological/biological effect from the last dosing before dosing day in the current study
• Coronavirus strain 19 (COVID-19) (severe acute respiratory syndrome - Coronavirus-2 (SARS CoV-2)):
• Has had COVID-19 infection within 4 weeks of the initial screening visit
• Positive coronavirus test (COVID-19: SARS-CoV-2 Polymerase chain reaction (PCR) or rapid antigen test) at initial screening
• Signs and symptoms suggestive of COVID-19 (i.e., fever, cough, etc.) within 14 days of initial screening Known COVID-19-positive contacts within 14 days of initial Screening, at any time during the Screening Period, or within 14 days of dosing on Day 1
• Active substance abuse or a history of substance abuse within 6 months prior to the initial Screening visit. Substance abuse including cannabis is also prohibited during the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: GSK1070806; Participants in Part A will receive single dose of GSK1070806 intravenous (IV) infusion	Drug: GSK1070806; Participants will receive GSK1070806
Experimental: Part B: GSK1070806; Participants in Part B will receive single dose of GSK1070806 IV bolus	Drug: GSK1070806; Participants will receive GSK1070806
Placebo Comparator: Part A: Placebo; Participants in Part A will receive single dose of placebo	Drug: Placebo; Participants will receive placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: Serum GSK1070806 area under the concentration-time curve from time zero extrapolated to infinity (AUC[0-∞])	Up to Week 24
Part A: Serum GSK1070806 area under the concentration-time curve from time zero to the last quantifiable time (AUC(0-t))	Up to Week 24
Part A: Maximum observed serum concentration (Cmax) of GSK1070806	Up to Week 24
Part A: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Part B: Number of participants with AEs and SAEs	Up to Week 32
Part A: Total IL-18 concentrations in serum	Up to Week 24
Part A: Number of participants with anti-drug antibody (ADA) formation	Up to Week 24
Part B: Number of participants with ADA formation	Up to Week 32
Part B: Total IL-18 concentrations in serum	Up to Week 32

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2022
• Primary Completion (Actual): July 12, 2023
• Study Completion (Actual): December 28, 2023

Study Registration Dates

• First Submitted: October 18, 2022
• First Submitted That Met QC Criteria: October 18, 2022
• First Posted (Actual): October 21, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Interleukin-18 (IL-18); GSK1070806; Immunoglobulin G1 (IgG1) antibody; 218841
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Dermatitis, Atopic
• Other Study ID Numbers: 218841

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 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: Yes
• Studies a U.S. FDA-regulated device product: No