NCT02446613

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

Completed Phase 2 Results posted Last updated 4 April 2018

What this trial tests

Phase 2 trial testing Pollen allergen extract in Asthma and Rhinitis in 16 participants. Completed in 10 August 2015.

Timeline

22 June 2015

Primary endpoint
10 August 2015

10 August 2015

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	single
Primary purpose	treatment
Enrollment	16
Start date	22 June 2015
Primary completion	10 August 2015
Estimated completion	10 August 2015
Sites	1 location across Canada

Drugs / interventions tested

• Pollen allergen extract

Conditions studied

• Asthma and Rhinitis — all drugs for Asthma and Rhinitis →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 65, any sex, with Asthma and Rhinitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change From Baseline in the Total Nasal Sym. Score (TNSS) at Post-NAC 15 Minutes (Min) Primary · Day 1 (Baseline [pre-NAC] and post-NAC 15 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.

Group	Value	95% CI
Placebo Once Weekly	3.8	1.22 – 6.53
GSK2245035 20 ng, i.n., Once Weekly	5.9	3.91 – 7.81

Mean Change From Baseline in the TNSS Over Post-NAC 1 h Primary · Day 1 (Baseline [pre-NAC], 15 to post-NAC 1h)

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.

Group	Value	95% CI
Placebo Once Weekly	2.4	0.24 – 4.63
GSK2245035 20 ng, i.n., Once Weekly	3.4	1.70 – 4.96

Mean Change From Baseline in the TNSS Over Post-NAC 6 h Primary · Day 1 (Baseline [pre-NAC] to 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.

Group	Value	95% CI
Placebo Once Weekly	1.2	0.04 – 2.33
GSK2245035 20 ng, i.n., Once Weekly	1.6	0.73 – 2.44

Maximum (Max) Mean Change From Baseline (BL) in the TNSS Over Post-NAC 6 h Primary · Day 1 (Baseline [pre-NAC] to 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 botherso

Group	Value	95% CI
Placebo Once Weekly	4.1	1.41 – 6.80
GSK2245035 20 ng, i.n., Once Weekly	5.9	3.83 – 7.87

Percent Change From Baseline in the Peak Nasal Inspiratory Flow (PNIF) at Post-NAC 15 Min Primary · Day 1 (Baseline [pre-NAC] and 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

Group	Value	95% CI
Placebo Once Weekly	27.6	15.87 – 39.63
GSK2245035 20 ng, i.n., Once Weekly	32.2	23.71 – 40.72

Percent Change From Baseline in the PNIF Over Post-NAC 1 h Primary · Day 1 (Baseline [pre-NAC] to 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 ca

Group	Value	95% CI
Placebo Once Weekly	20.8	5.45 – 35.84
GSK2245035 20 ng, i.n., Once Weekly	25.0	14.69 – 36.05

Percent Change From Baseline in the PNIF up to Post-NAC 6 h Primary · Day 1 (Baseline [pre-NAC] 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 tim

Group	Value	95% CI
Placebo Once Weekly	6.3	-7.56 – 20.47
GSK2245035 20 ng, i.n., Once Weekly	7.3	-2.98 – 17.68

Maximum Percent Change From Baseline in PINF Over Post-NAC 6 h Primary · Day 1 (Baseline [pre-NAC] 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). Maximum change from Baseline till 6h was reported.

Group	Value	95% CI
Placebo Once Weekly	33.3	16.89 – 49.33
GSK2245035 20 ng, i.n., Once Weekly	39.9	29.18 – 51.53

Mean Change From Baseline in Individual Nasal Sym. Including Sneezing, Nasal Congestion, Rhinorrhoea and Nasal Itch. Secondary · Day 1 (Baseline [pre-NAC] to post-NAC 6 h)

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= Mo

Sneezing, 15 min

Group	Value	95% CI
Placebo Once Weekly	1.33	± 1.366
GSK2245035 20 ng, i.n., Once Weekly	1.50	± 1.080

Sneezing, WM 0-1 h

Group	Value	95% CI
Placebo Once Weekly	0.56	± 0.706
GSK2245035 20 ng, i.n., Once Weekly	0.56	± 0.641

Sneezing, WM 0-6 h

Group	Value	95% CI
Placebo Once Weekly	0.40	± 0.496
GSK2245035 20 ng, i.n., Once Weekly	0.19	± 0.463

Sneezing, Max 0-6 h

Group	Value	95% CI
Placebo Once Weekly	1.33	± 1.366
GSK2245035 20 ng, i.n., Once Weekly	1.60	± 1.075

Rhinorrhoea, 15 min

Group	Value	95% CI
Placebo Once Weekly	0.50	± 0.548
GSK2245035 20 ng, i.n., Once Weekly	1.60	± 1.075

Rhinorrhoea, WM 0-1 h

Group	Value	95% CI
Placebo Once Weekly	0.15	± 0.300
GSK2245035 20 ng, i.n., Once Weekly	1.16	± 0.924

Rhinorrhoea, WM 0-6 h

Group	Value	95% CI
Placebo Once Weekly	-0.06	± 0.383
GSK2245035 20 ng, i.n., Once Weekly	0.60	± 0.791

Rhinorrhoea, Max 0-6 h

Group	Value	95% CI
Placebo Once Weekly	0.50	± 0.548
GSK2245035 20 ng, i.n., Once Weekly	1.60	± 1.075

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events (SAEs) were collected from participant's consent for participation in the study till follow-up contact (4 to 7 day post Visit 2). Adverse events (AEs) were collected from the start of Study Visit 2 NAC until the follow-up contact.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Once Weekly

Serious: 0/6 (0%)

Deaths: —

GSK2245035 20 ng, i.n., Once Weekly

Serious: 0/10 (0%)

Deaths: —

Other adverse events (2 terms — click to expand)

Reaction	System	Placebo Once Weekly	GSK2245035 20 ng, i.n., On…
Urinary tract infection	Infections and infestations	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—

Data from ClinicalTrials.gov NCT02446613 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Toll-like receptor signalling in B cells during systemic lupus erythematosus.
   Fillatreau S, Manfroi B, Dörner T. · · 2021 · cited 229× · PMID 33339987 · DOI 10.1038/s41584-020-00544-4
2. Safety and pharmacodynamics of intranasal GSK2245035, a TLR7 agonist for allergic rhinitis: A randomized trial.
   Ellis AK, Tsitoura DC, Quint D, Powley W, et al · · 2017 · cited 26× · PMID 28681506 · DOI 10.1111/cea.12974
3. Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016
   Alsayegh M, Alshamali H, Khadada M, Ciccolini A, et al · · 2017