Efficacy and Safety of GSK3923868 Inhalation Powder, During Experimental Human Rhinovirus Infection in Participants With Mild Asthma

A Randomized, Double-blind, Placebo Controlled, Repeat Dose Phase 1b Study to Assess the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled GSK3923868 During Experimental Human Rhinovirus Infection in Participants With Mild Asthma

This is a Phase 1b, single center study designed to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK3923868 following repeat doses in mild asthmatics during experimental human rhinovirus 16 (HRV-16) infection. The study will be conducted in two parts. Part A will determine the efficacy of GSK3923868 administration after viral inoculation (i.e., therapeutic treatment) and Part B may be undertaken to determine the efficacy of GSK3923868 administration before viral inoculation (i.e., prophylactic treatment). The purpose of this study is to establish proof-of-mechanism that GSK3923868 treatment can reduce symptoms of Human Rhinovirus (HRV) infection in a controlled setting.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: GSK3923868; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, E1 2AX
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All Participant aged between 18 to 65 years of age (inclusive).
• Participants with a diagnosis of asthma.
• A screening pre-bronchodilator FEV1 greater than or equal to (≥) 65 percentage (%) predicted normal value.
• Positive Methacholine challenge test, defined as ≥ 20% fall in FEV1 at a methacholine concentration less than or equal to (≤) 16 milligram/milliliter (mg/mL) at Screening.

If the methacholine challenge test is negative or the participant is unable to perform this test, bronchodilator reversibility is allowed as an alternative, assessed as follows:

• Positive bronchodilator reversibility test, defined as an increase in FEV1 >12% and >200 mL from baseline, 10 to 15 minutes after administration of 400 micrograms (mcg) salbutamol (or equivalent).
• Participants with positive skin prick test.
• The HRV-16 neutralization antibody assay indicates that the participant will be susceptible to HRV-16 infection.
• Participants with controlled asthma, using short-acting beta agonist (SABA) or intermittent inhaled corticosteroid (ICS) or ICS/ long-acting beta agonist (LABA) therapy.
• Male and female- A female participant is eligible to participate if she is not pregnant or breastfeeding.
• Participant capable of giving signed informed consent.

Exclusion Criteria:

All participants:

• Any asthma exacerbation requiring systemic corticosteroids within 8 weeks of admission, or that resulted in overnight hospitalization requiring additional treatment for asthma within 3 months of admission.
• History of life-threatening asthma, defined as any asthma episode that required admission to a high-dependency or intensive therapy unit.
• The presence of concurrent significant pulmonary diseases, other than asthma, including bronchiectasis, pulmonary fibrosis, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other significant respiratory abnormalities.
• Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the study.
• Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months of admission and/or history of being hospitalized due to epistaxis on any previous occasion.
• Any nasal or sinus surgery within 3 months of admission with any acute illness, including a common cold or other respiratory tract infection within 6 weeks before admission.
• Any major illness or hospitalization within 6 months before admission to the unit.
• Lifetime history of anaphylaxis or severe allergic reaction or significant intolerance to any food or drug.
• Fridericia's QT correction formula (QTcF) >450 millisecond (msec) on Day -1 based on the average of triplicate ECGs.
• Evidence of vaccinations within the 4 weeks prior to the planned date of viral challenge.
• Intention to receive any vaccination before the last day of follow up.
• Prior participation in another Human Viral Challenge study with a respiratory virus in the preceding 12 months.
• Positive pathogen screen for respiratory tract infection
• History of regular use of tobacco or nicotine-containing products.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK3923868; All participants in this arm will receive GSK3923868	Drug: GSK3923868; GSK3923868 dose and administration as per study intervention.
Placebo Comparator: Placebo; All participants in this arm will receive matching placebo	Drug: Placebo; Placebo matching GSK3923868 will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under curve (AUC) of change from baseline (CfB) in total lower respiratory tract symptoms (LRTS) score from day of inoculation up to discharge	The LRTS includes cough, chest tightness, shortness of breath, wheezing, daily activity, and night time awakenings. Each symptom is assessed on a 4-point scale. The score ranges from 0 to 3, where higher points indicate more symptoms experienced and severity that restricts normal activities. Shortness of breath and wheezing will be measured on a 5-point scale and ranges from 0 to 4 in which 0 indicates no symptoms and 4 indicates symptoms at total rest and the highest level of disease severity. LRTS assessment is performed three times a day.	Baseline and up to Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal CfB in total LRTS score from day of inoculation up to discharge		Baseline and up to Day 15
AUC and maximal CfB in total upper respiratory tract symptoms (URTS) score from day of inoculation up to discharge	The URTS includes nasal discharge, nasal obstruction, sneezing and sore throat. Each symptom will be assessed on a 4-point scale, where 0 indicates no symptom and a higher point for more symptoms and severity that restricts normal activities.	Baseline and up to Day 15
Number of participants with adverse events (AEs) and serious adverse events (SAEs)		Up to Day 22
Number of participants with clinically significant changes in vital signs		Up to Day 22
Number of participants with clinically significant changes in electrocardiogram (ECG)		Up to Day 22
Number of participants with clinically significant changes in clinical laboratory parameters		Up to Day 22
Mean percent CfB and maximum percent decline from baseline in trough force expiratory volume (FEV1) from day of inoculation up to discharge		Baseline and up to Day 15
Mean percent CfB and maximum percent decline from baseline in morning and evening peak expiratory flow (PEF) from day of inoculation up to discharge		Baseline and up to Day 15

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Actual): April 9, 2024
• Study Completion (Actual): April 9, 2024

Study Registration Dates

• First Submitted: May 26, 2022
• First Submitted That Met QC Criteria: May 26, 2022
• First Posted (Actual): May 31, 2022

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Pharmacokinetics; Pharmacodynamics; Chronic Obstructive Pulmonary Disease (COPD); Respiration Disorders; GSK3923868; Human Rhinovirus (HRV); Viral Challenge
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Lung Diseases, Obstructive; Chronic Disease; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 213499; 2021-006640-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No