Clinical trial NCT05398198: Efficacy and Safety of GSK3923868 Inhalation Powder, During Experimental Human Rhinovirus Infection in Participants With Mild Asthma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: GSK3923868
Chronic Obstructive Pulmonary Disease (COPD)
Respiratory Tract Diseases
Respiration Disorders
Pharmacokinetics
Pharmacodynamics
Human Rhinovirus (HRV)
Viral Challenge
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-05-31
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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, 3 and 4 days post-viral inoculation for cohort 1 and 2.

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.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Area under curve (AUC) of change from baseline (CfB) in total lower respiratory tract symptoms (LRTS) score from day of inoculation up to discharge
timeFrame: Baseline and up to Day 15
Secondary outcomes:
measure: Maximal CfB in total LRTS score from day of inoculation up to discharge
timeFrame: Baseline and up to Day 15
measure: AUC and maximal CfB in total upper respiratory tract symptoms (URTS) score from day of inoculation up to discharge
timeFrame: Baseline and up to Day 15
measure: Mean percent CfB and maximum percent decline from baseline in trough force expiratory volume (FEV1) from day of inoculation up to discharge
timeFrame: Baseline and up to Day 15
measure: Mean percent CfB and maximum percent decline from baseline in morning and evening peak expiratory flow (PEF) from day of inoculation up to discharge
timeFrame: Baseline and up to Day 15
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to Day 22
measure: Number of participants with clinically significant changes in vital signs
timeFrame: Up to Day 22
measure: Number of participants with clinically significant changes in electrocardiogram (ECG)
timeFrame: Up to Day 22
measure: Number of participants with clinically significant changes in clinical laboratory parameters
timeFrame: Up to Day 22
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: