GSK2245035 is a highly selective Toll-like receptor 7 (TLR7) agonist that stimulates preferentially the induction of type I interferons. Intranasal (i.n.) administration of GSK2245035 in humans causes immune changes in the upper airways milieu that may alter bystander immune responsiveness to aeroallergens and contribute to reduction of allergic reactivity in subjects with respiratory allergies. The purpose of this study is to examine the safety and pharmacodynamics (PD) of repeat dosing with i.n. GSK2245035 in subjects with respiratory allergies. The safety and pharmacodynamic response of four weekly administrations of escalating doses of i.n. GSK2245035 will be investigated and the maximum tolerated dose will be established. The study will be conducted in patients with symptomatic allergic rhinitis and mild asthma. The overall duration of the study will be up to a maximum of approximately 122 days considering 90 days screening period, 22 days treatment period and 10 days follow-up period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
18
GSK2245035 nasal spray solution. A solution formulation in saline, preserved with Benzalkonium Chloride and Disodium Edetate
fitted with a metered Valios VP7 pump
As for GSK2245035 nasal spray solution except for omission of the active ingredient
GSK Investigational Site
Toronto, Ontario, Canada
Number of participants experiencing adverse events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Up to 122 Days
Hematology parameters as a safety measure
The hematology parameters included are platelet count, red blood cell (RBC) count, white blood cell (WBC) count, reticulocyte count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils, basophils.
Time frame: Up to 112 Days
Clinical Chemistry parameters as a safety measure
Clinical chemistry parameters included are blood urea nitrogen (BUN), creatinine, glucose, potassium, C-Reactive protein (CRP) potassium, chloride, total carbon dioxide, calcium, total and direct bilirubin, Aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase, uric acid, protein and albumin
Time frame: Up to 112 Days
Urinalysis parameters as a safety measure
Urinalysis parameters included are specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick, microscopic examination (if blood or protein is abnormal)
Time frame: Up to 112 Days
Body temperature
Time frame: Up to 112 Days
Systolic and diastolic blood pressure (BP)
Time frame: Up to 112 Days
Pulse rate
Time frame: Up to 112 Days
ECG parameters
A 12 lead electrocardiogram (ECG) will be measured using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
Time frame: Up to 112 Days
Nasal examination
Visual nasal examination will be conducted by a trained physician
Time frame: Up to 112 Days
Nasal symptoms assessment
Nasal tolerability symptoms itching, discomfort, post-nasal drip, rhinorrhoea, obstruction will be assessed using a Visual analogue score system
Time frame: Up to 23 Days
FEV1 assessment
To evaluate the effect of four repeat doses of i.n. GSK2245035 administered once per week on lung function, as measured by Forced expiratory volume in one second FEV1
Time frame: Up to 112 Days
TLR7-induced blood PD biomarkers, including TLR7-induced cytokines
To evaluate the induction of TLR7-associated blood PD biomarkers following administration of i.n. GSK2245035 once per week
Time frame: Up to 23 Days
TLR7-induced nasal PD biomarkers, including but not limited to induced protein (IP)-10, i.n. nasal lavage fluid
To evaluate the induction of TLR7-associated nasal PD biomarkers following administration of repeat doses of i.n. GSK2245035 once per week
Time frame: Up to 23 Days
Daily rhinitis symptoms and use of medication diaries during the study period
Time frame: Up to 122 Days
Daily asthma symptoms and use of medication diaries during the study period
Time frame: Up to 122 Days
Daily morning peak expiratory flow (PEF) during the study period
Time frame: Up to 112 Days
Exhaled NO assessment
Time frame: Up to 23 Days
Cell counts and differential in nasal lavage
Time frame: Up to 23 Days
Exploratory allergic biomarkers including but not limited to immunoglobulins and cytokines in blood and nasal lavage fluid and tissue
Time frame: Up to 23 Days
Plasma GSK2245035 concentrations
Time frame: Up to 23 Days
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