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

• ClinicalTrials.gov Identifier: NCT05398198
• Recruitment Status: Recruiting
• First Posted: May 31, 2022
• Last Update Posted: December 1, 2022
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: GSK3923868; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

Part A: In therapeutic treatment cohorts (cohort 1 and 2) repeat doses of GSK3923868 are administered after experimental viral infection with increasing time windows between viral inoculation and the initiation of study drug. The treatment is initiated 2 and 4 days post-viral inoculation for cohort 1 and 2 respectively.

Part B: In prophylactic treatment cohort (cohort 3), treatment is initiated before inoculation with virus.

Of 3 cohorts planned, two cohorts will be performed (Cohort 1 and either Cohort 2 or 3). Cohort 1 data will be used to determine which cohort to progress to along with any study design changes.

• Masking: Double (Participant, Investigator)
• Masking Description: The participants and site staff will be blinded to the study intervention.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 9, 2022
• Estimated Primary Completion Date: July 27, 2023
• Estimated Study Completion Date: July 27, 2023

Arms and Interventions

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 administered.

Outcome Measures

Primary Outcome Measures :

1. Area under curve (AUC) of change from baseline (CfB) in total lower respiratory tract symptoms (LRTS) score from day of inoculation up to discharge [ Time Frame: Baseline and up to Day 15 ]
   The LRTS includes cough, chest tightness, shortness of breath, wheezing, daily activity, and nighttime 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.

Secondary Outcome Measures :

1. Maximal CfB in total LRTS score from day of inoculation up to discharge [ Time Frame: Baseline and up to Day 15 ]
2. AUC and maximal CfB in total upper respiratory tract symptoms (URTS) score from day of inoculation up to discharge [ Time Frame: Baseline and up to Day 15 ]
   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.
3. AUC and maximum decline from baseline in trough force expiratory volume (FEV1) from day of inoculation up to discharge [ Time Frame: Baseline and up to Day 15 ]
4. AUC and maximum decline from baseline in morning and evening peak expiratory flow (PEF) from day of inoculation up to discharge [ Time Frame: Baseline and up to Day 15 ]
5. Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to Day 22 ]
6. Number of participants with clinically significant changes in vital signs [ Time Frame: Up to Day 22 ]
7. Number of participants with clinically significant changes in electrocardiogram (ECG) [ Time Frame: Up to Day 22 ]
8. Number of participants with clinically significant changes in clinical laboratory parameters [ Time Frame: Up to Day 22 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Locations

United Kingdom

GSK Investigational Site; Recruiting

London, United Kingdom, E1 2AX

Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Centre +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com

Principal Investigator: Melissa Bevan

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT05398198
• Other Study ID Numbers: 213499; 2021-006640-27 ( EudraCT Number )
• First Posted: May 31, 2022
• Last Update Posted: December 1, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• 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.
• 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.
• URL: http://clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

GSK3923868; Chronic Obstructive Pulmonary Disease (COPD); Respiratory Tract Diseases; Respiration Disorders; Pharmacokinetics; Pharmacodynamics; Human Rhinovirus (HRV); Viral Challenge

Additional relevant MeSH terms:

Lung Diseases; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Lung Diseases, Obstructive