Follow-up Study to Investigate the Effect of GSK2245035 on Nasal Allergic Reactivity in Subjects Completing Treatment in Study TL7116958

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the duration of effect of GSK2245035 on allergic reactivity by repeating a nasal allergen challenge (NAC) approximately one year after treatment in subjects from TL7116958. This is a single centre, single period study in subjects with respiratory allergy/allergies who completed the study TL7116958 in 2014 to investigate the long term effect of previous treatment with GSK2245035 compared with placebo on total nasal symptoms elicited by nasal allergen challenge. Subjects and staff will remain blinded to the treatment received in the TL7116958 study (GSK2245035 or placebo). The study will consist of a screening visit to assess eligibility criteria, a study period consisting of a single visit when the nasal allergen challenge will be performed, and follow up by phone or a clinic visit at the discretion of the investigator 4-7 days following the allergen challenge. Eligible subjects will participate in this study for approximately70 days total from screening to follow up.

Official Title
-----------------
A Single-centre, Follow-up Study to Investigate the Effect of GSK2245035 on Nasal Allergic Reactivity in Subjects Who Completed Treatment in Study TL7116958 in 2014

Conditions
-----------------
Asthma and Rhinitis

Intervention / Treatment
-----------------
* Other: Pollen allergen extract


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult subjects with allergic rhinitis who completed study TL7116958 in 2014. Healthy as determined by the investigator or medically qualified designee based on a brief physical examination. Males and non-pregnant females. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Exclusion Criteria: Unresolved respiratory tract infection (RTI) at the time of study visit 2 NAC. Investigator discretion will be used regarding RTIs that have resolved during the 4 weeks preceding study visit 2. Unresolved asthma exacerbation requiring hospitalization and/or treatment with oral steroids or high doses of inhaled steroids at the time of study visit 2 NAC. Investigator discretion will be used regarding exacerbations that have resolved since screening visit. A change in medical history since completion of the study TLR7116958 that in the opinion of the investigator and GlaxoSmithKline (GSK) medical monitor may pose additional risk factors. Subjects with a history of treatment with allergen-specific immunotherapy since completion of the TL7116958 study; subjects that have taken an investigational drug that, in the opinion of the investigator or designee, would have an effect on the nasal allergen challenge Subjects using steroid treatment (nasal steroids, 4 weeks; oral steroids, 4 weeks; inhaled steroids, 4 weeks) for allergic rhinitis and/or asthma prior to study visit 2, nasal allergen challenge Subjects using antihistamines (nasal antihistamines, 48 hours; oral antihistamines 72 hours), decongestants (nasal decongestants, 24 hours; oral decongestants, 24 hours.), prior to study visit 2, nasal allergen challenge. Subject is mentally or legally incapacitated.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Nasal allergen challenge<br>Subjects do not receive study medication in this study 204509. Subjects who carried from study TL7116958 treatment group GSK2245035 will undergo NAC with pollen allergen extract. | Other: Pollen allergen extract<br>* Pollen (tree, grass or ragweed) allergen extracts will be provided by the research unit and diluted as required in normal saline. The specific pollen allergen extract that will be used for the nasal allergen challenge will be selected according to each subject's individual allergic sensitivity demonstrated in the previous study, TL7116958. If possible, extracts remaining from this study in 2014 will be used, provided they have not reached their expiry date.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Total Nasal Sym. Score (TNSS) at Post-NAC 15 Minutes (Min) | TNSS was obtained from 4 individual nasal sym. including nasal congestion, rhinorrhoea, nasal itch and sneezing. Participants rated sym. on a 4-point scale. For nasal blockage and congestion the scores were (0= Breathing through nose freely and easily, 1= Slight difficulty breathing through nose, 2= Moderate difficulty breathing through nose and 3= Severe difficulty breathing through nose). For rhinorrhoea, nasal itching and sneezing (0= None: No sym. whatsoever; Absent, 1= Mild: Sym. is present, noticeable but not bothersome, 2= Moderate: Sym. is bothersome, but tolerable and 3= Severe: Sym. which are bothersome, harder to tolerate). The individual sym. scores were combined to produce a TNSS. TNSS were reported as median (credible interval). The baseline values were the latest pre-dose assessments. Change from baseline was measured as the value recorded at 15 min post-NAC minus Baseline value. | Day 1 (Baseline [pre-NAC] and post-NAC 15 min) | 
| Mean Change From Baseline in the TNSS Over Post-NAC 1 h | TNSS was obtained from 4 individual nasal sym. including nasal congestion, rhinorrhoea, nasal itch and sneezing. Participants rated sym. on a 4-point scale. For nasal blockage and congestion the scores were (0= Breathing through nose freely and easily, 1= Slight difficulty breathing through nose, 2= Moderate difficulty breathing through nose and 3= Severe difficulty breathing through nose). For rhinorrhoea, nasal itching and sneezing (0= None: No sym. whatsoever; Absent, 1= Mild: Sym. is present, noticeable but not bothersome, 2= Moderate: Sym. is bothersome, but tolerable and 3= Severe: Sym. which are bothersome, harder to tolerate). The individual sym scores were combined to produce a TNSS. TNSS were reported as median (credible interval). The baseline values were the latest pre-dose assessments. Change from baseline was measured as the value recorded at a specified time point minus Baseline value. Weighted mean (WM) 0-1h of 15, 30 min and 1 h was reported. | Day 1 (Baseline [pre-NAC], 15 to post-NAC 1h) | 
| Mean Change From Baseline in the TNSS Over Post-NAC 6 h | TNSS was obtained from 4 individual nasal sym. including nasal congestion, rhinorrhoea, nasal itch and sneezing. Participants rated sym. on a 4-point scale. For nasal blockage and congestion the scores were (0= Breathing through nose freely and easily, 1= Slight difficulty breathing through nose, 2= Moderate difficulty breathing through nose and 3= Severe difficulty breathing through nose). For rhinorrhoea, nasal itching and sneezing (0= None: No sym. whatsoever; Absent, 1= Mild: Sym. is present, noticeable but not bothersome, 2= Moderate: Sym. is bothersome, but tolerable and 3= Severe: Sym. which are bothersome, harder to tolerate). The individual sym scores were combined to produce a TNSS. TNSS were reported as median (credible interval). The baseline values were the latest pre-dose assessments. Change from baseline was measured as value recorded at a specified time point minus Baseline value. WM 0-6 h of 15, 30 min, 1, 2, 3, 4, 5, 6h was reported. | Day 1 (Baseline [pre-NAC] to post-NAC 6 h) | 
| Maximum (Max) Mean Change From Baseline (BL) in the TNSS Over Post-NAC 6 h | TNSS was obtained from 4 individual nasal sym.: nasal congestion, rhinorrhoea, nasal itch and sneezing. Par rated sym. on a 4-point scale. For nasal blockage and congestion the scores were (0= Breathing through nose freely and easily, 1= Slight difficulty breathing through nose, 2= Moderate difficulty breathing through nose and 3= Severe difficulty breathing through nose). For rhinorrhoea, nasal itching and sneezing (0= None: No sym. whatsoever; Absent, 1= Mild: Sym. is present, noticeable but not bothersome, 2= Moderate: Sym. is bothersome, but tolerable and 3= Severe: Sym. which are bothersome, harder to tolerate). The individual sym. scores were combined to produce a TNSS. TNSS were reported as median (credible interval). BL values were the latest pre-dose assessments. Change from BL was measured as the value recorded at a specified time point minus BL value. The max change from BL from the set of individual PNIF % reduction measurements made over the 0 to 6 h sampling period. | Day 1 (Baseline [pre-NAC] to post-NAC 6 h) | 
| Percent Change From Baseline in the Peak Nasal Inspiratory Flow (PNIF) at Post-NAC 15 Min | PNIF data recorded at Baseline pre-challenge and at 15, 30 min and 1h. The percent change from Baseline and at specified time point was derived by the formula (PNIF at Baseline minus PNIF at Post-NAC specified time point) divided by PNIF at Baseline) multiplied by 100. The baseline values were the latest pre-dose assessments. The baseline value were the latest pre-dose assessments. Percent change in PNIF were reported as median (credible interval). WM 0-1 h of 15, 30 min and 1 h was reported. WM were derived by first calculating the AUC using the trapezoidal rule, and then dividing by the time interval. If available, actual times were used in the calculation, otherwise planned relative times were used for the calculation. | Day 1 (Baseline [pre-NAC] and post-NAC 15 min) | 
| Percent Change From Baseline in the PNIF Over Post-NAC 1 h | PNIF data recorded at Baseline pre-challenge and at 15, 30 min and 1h. The percent change from Baseline and at specified time point was derived by the formula (PNIF at Baseline minus PNIF at Post-NAC specified time point) divided by PNIF at Baseline) multiplied by 100. The baseline values were the latest pre-dose assessments. Percent change in PNIF were reported as median (credible interval). WM 0-1 h of 15, 30 min and 1 h was reported. WM were derived by first calculating the AUC using the trapezoidal rule, and then dividing by the time interval. If available, actual times were used in the calculation, otherwise planned relative times were used for the calculation. | Day 1 (Baseline [pre-NAC] to post-NAC 1 h) | 
| Percent Change From Baseline in the PNIF up to Post-NAC 6 h | PNIF data recorded at Baseline pre-challenge and at 15, 30 min, 1, 2, 3, 4, 5, 6h. The percent change from Baseline and at specified time point was derived by the formula (PNIF at Baseline minus PNIF at Post-NAC specified time point) divided by PNIF at Baseline) multiplied by 100. The baseline values were the latest pre-dose assessments. Percent change in PNIF were reported as median (credible interval). WM 0-6h of 15, 30 min, 1, 2, 3, 4, 5, 6h was reported. WM were derived by first calculating the AUC using the trapezoidal rule, and then dividing by the time interval. If available, actual times were used in the calculation, otherwise planned relative times were used for the calculation. | Day 1 (Baseline [pre-NAC] to post-NAC 6 h) | 
| Maximum Percent Change From Baseline in PINF Over Post-NAC 6 h | PNIF data recorded at Baseline pre-challenge and at 15, 30 min, 1, 2, 3, 4, 5, 6h. The percent change from Baseline and at specified time point was derived by the formula (PNIF at Baseline minus PNIF at Post-NAC specified time point) divided by PNIF at Baseline) multiplied by 100. The baseline values were the latest pre-dose assessments. Percent change in PNIF were reported as median (credible interval). Maximum change from Baseline till 6h was reported. | Day 1 (Baseline [pre-NAC] to post-NAC 6 h) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Individual Nasal Sym. Including Sneezing, Nasal Congestion, Rhinorrhoea and Nasal Itch. | Four individual nasal sym. including nasal congestion, rhinorrhoea, nasal itch and sneezing were recorded at Baseline (pre-NAC) and at post-NAC 15, 30 min, 1, 2, 3, 4, 5, 6h. Participants rated sym. on a 4-point scale. For nasal blockage and congestion the scores were (0= Breathing through nose freely and easily, 1= Slight difficulty breathing through nose, 2= Moderate difficulty breathing through nose and 3= Severe difficulty breathing through nose). For rhinorrhoea, nasal itching and sneezing (0= None: No sym. whatsoever; Absent, 1= Mild: Sym. is present, noticeable but not bothersome, 2= Moderate: Sym. is bothersome, but tolerable and 3= Severe: Sym. which are bothersome, harder to tolerate). The baseline value were the latest pre-dose assessments. Mean change from Baseline at 15 min, WM0-1h, WM 0-6h, and maximum change over 0-6 h were reported. Change from Baseline was measured as the value recorded at a specified time point minus Baseline value. | Day 1 (Baseline [pre-NAC] to post-NAC 6 h) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Allergic Rhinitis, Nasal allergen challenge, Allergic Asthma, Effect on Allergen Reactivity