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Effect of the GSK2245035 on the Allergen-induced Asthmatic Response

Phase 2
Completed
Conditions
Asthma
Interventions
Drug: GSK2245035 Nasal Spray Solution
Drug: Placebo Nasal Spray Solution
Registration Number
NCT02833974
Lead Sponsor
GlaxoSmithKline
Brief Summary

This study will assess whether Toll like receptor 7 (TLR7)-mediated pharmacology, with intranasal (i.n.) GSK2245035 20 nanogram (ng) administered weekly for a period of 8 weeks, will lead to reduced allergic reactivity in the lower airways in subjects with mild allergic asthma.

This will be a randomised, double-blind (sponsor open), placebo-controlled, parallel group, 8-week treatment study.

The study will consist of a screening period of up to approximately 4 weeks (involving two screening visits), a blinded treatment period of 8 weeks, followed by a follow-up period of up to 3 months. The total duration of the study for each subject will therefore be a maximum of approximately 6 months.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
GSK2245035 20 ngGSK2245035 Nasal Spray SolutionParticipants will receive 20 ng of GSK2245035 Nasal spray solution (1 spray=10 ng GSK2245035 per actuation per nostril) every week for the duration of 8 weeks administered using a metered Valois VP7 pump
PlaceboPlacebo Nasal Spray SolutionParticipants will receive placebo Nasal spray solution (1 spray per nostril) every week for the duration of 8 weeks administered using a metered Valois VP7 pump
Primary Outcome Measures
NameTimeMethod
Late Asthmatic Response (LAR): Absolute Change From Saline in Minimum Forced Expiratory Volume in 1 Second (FEV1) Between 4-10 Hours Following Allergen Challenge One Week After TreatmentWeek 9

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to bronchial allergen challenge (BAC) at the one-week follow-up visit (one week after the eighth dose of the study treatment). Minimum FEV1 over 4-10 hours post-allergen challenge (minimum LAR) is the minimum value of all of the post-saline time points between 4 and 10 hours post-allergen challenge, inclusive of the 4 and 10 hours timepoints. Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value. Per-Protocol Population comprises of all randomized participants who received at least one dose of study treatment and commence a BAC at follow-up and comply with the protocol.

LAR: Absolute Change From Saline in Weighted Mean FEV1 Between 4-10 Hours Following Allergen Challenge One Week After TreatmentWeek 9

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to BAC at the one-week follow-up visit (one week after the eighth dose of the study treatment). Weighted mean FEV1 over 4-10 hours post-allergen challenge includes all post-saline time points between 4 and 10 hours post-allergen challenge, inclusive of the 4 and 10 hours timepoints. The weighted mean FEV1 was derived by calculating the area under the curve, and dividing the value by the relevant time interval. Absolute change from saline at each time point was calculated as the highest allergen challenge FEV1 value minus the highest saline FEV1 value.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Abnormal Peak Expiratory Flow (PEF)Up to Week 12

The PEF is defined as the greatest rate of airflow that can be achieved during forced exhalation beginning with the lungs fully inflated. Participants were instructed to record their PEF readings each morning and evening into the diary card that was provided by the investigator. The minimum and maximum range ranges for PEF were \<=205 and \>=980 liters per minute.

Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hours Following Allergen Challenge One Week After TreatmentWeek 9

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to BAC at the one-week follow-up visit (one week after the eighth dose of the study treatment). Minimum FEV1 over 0-2 hours post-allergen challenge (minimum LAR) is the minimum value of all of the post-saline time points between 0 and 2 hours post-allergen challenge, inclusive of the 0 and 2 hours timepoints. Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value.

EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hours Following Allergen Challenge One Week After Treatment.Week 9

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to BAC at the one-week follow-up visit (one week after the eighth dose of the study treatment). Weighted mean FEV1 over 0-2 hours post-allergen challenge includes all post-saline time points between 0-2 hours post-allergen challenge, inclusive of 0 and 2 hours timepoints. The weighted mean FEV1 was derived by calculating the area under the curve, and dividing the value by the relevant time interval. Absolute change from saline at each time point was calculated as the highest allergen challenge FEV1 value minus the highest saline FEV1 value.

Number of Participants With Hematology Values of Potential Clinical ConcernUp to Week 20

Blood samples were collected for analysis of hematology parameters. Hematology parameters included hematocrit, hemoglobin, platelet count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and red blood cells (RBC).

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)Up to Week 20

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AEs and SAEs have been reported.

Number of Participants With Clinical Chemistry Values of Potential Clinical ConcernUp to Week 8

Blood samples were collected for analysis of clinical chemistry parameters. Clinical chemistry parameters included blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, total and direct bilirubin, albumin, calcium, creatinine, glucose, potassium and sodium.

Number of Participants Receiving Rescue MedicationUp to Week 20

Salbutamol was administered as rescue medication only to participants who experienced serious discomfort. The data below exclude any Salbutamol administered as part of the planned study procedures (for example the Salbutamol administered after the Bronchial Allergen Challenge \[BAC\] is not counted as a rescue medication).

Number of Participants With Abnormal Urine Analysis FindingsUp to Week 8

Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.

Trial Locations

Locations (1)

GSK Investigational Site

🇬🇧

Manchester, United Kingdom

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