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

NCT05590338 | Completed Phase 1 FDA Drug

• 1 other identifier: 218841
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Dermatitis, Atopic

Keywords

Immunoglobulin G1 (IgG1) antibody; Interleukin-18 (IL-18); GSK1070806; 218841

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• 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 B: Total IL-18 concentrations in serum

  Up to Week 32

• 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

Study Arms (3)

Part A: GSK1070806

EXPERIMENTAL

Participants in Part A will receive single dose of GSK1070806 intravenous (IV) infusion

Drug: GSK1070806

Part B: GSK1070806

EXPERIMENTAL

Participants in Part B will receive single dose of GSK1070806 IV bolus

Drug: GSK1070806

Part A: Placebo

PLACEBO COMPARATOR

Participants in Part A will receive single dose of placebo

Drug: Placebo

Interventions

GSK1070806 DRUG

Participants will receive GSK1070806

Part A: GSK1070806; Part B: GSK1070806

Placebo DRUG

Participants will receive placebo

Part A: Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Cypress, California, 90630, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

GSK1070806

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: In Part A the participants and investigators will be masked. In Part B there will be no masking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Part A the participants will be randomly assigned in each arm to receive either active or placebo interventions. In Part B the participants will be assigned to receive only active intervention.

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 21, 2022
• Study Start: November 4, 2022
• Primary Completion: July 12, 2023
• Study Completion: December 28, 2023
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

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

Locations

US (2)