Effect of the GSK2245035 on the Allergen-induced Asthmatic Response

NCT02833974 | Completed Phase 2 Results

• 2 other identifiers: 2055402015-005645-31
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 6

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.

Conditions

Asthma

Keywords

GSK2245035; TLR7 agonist; allergic asthma; FEV1

Outcome Measures

Primary Outcomes (2)

• 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 Treatment

  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.

  Week 9

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

  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.

  Week 9

Secondary Outcomes (8)

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

  Week 9

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

  Week 9

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Week 20

• Number of Participants With Abnormal Peak Expiratory Flow (PEF)

  Up to Week 12

• Number of Participants Receiving Rescue Medication

  Up to Week 20

Study Arms (2)

GSK2245035 20 ng

EXPERIMENTAL

Participants 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

Drug: GSK2245035 Nasal Spray Solution

Placebo

PLACEBO COMPARATOR

Participants 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

Drug: Placebo Nasal Spray Solution

Interventions

GSK2245035 Nasal Spray Solution DRUG

GSK2245035 Nasal Spray Solution 0.2 microgram (mcg)/mL delivering 10 ng GSK2245035 per actuation. A solution formulation in saline, preserved with Benzalkonium Chloride and Disodium Edetate.

GSK2245035 20 ng

Placebo Nasal Spray Solution DRUG

Nasal Spray Solution as for GSK2245035 without active ingredient.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• Diagnosis of asthma, as defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation for at least 6 months prior to screening
• Current asthma therapy. Intermittent short-acting beta-agonist (SABA) alone (on average for no more than 2 days per week)
• Positive skin prick test (3 mm or more greater than negative control) to common perennial or seasonal aeroallergen(s) (i.e., house dust mite, cat dander, grass pollen) at screening
• Pre-bronchodilator FEV1 \> 70 % predicted normal at Screening Visit 1
• EAR with \>=20 % FEV1 decrease between 5 and 30 minutes after the final allergen concentration is obtained at the screening bronchial allergen challenge (BAC) (decreases relative to the saline)
• LAR with three FEV1 decreases of \>= 15 % between 4 and 10 hours after the final allergen concentration is obtained at the screening bronchial allergen challenge, with two FEV1 decreases being at consecutive time points (decreases relative to the saline)
• Subjects who are current non-smokers (defined as no use of any tobacco products in the 6-month period preceding the screening visit) and have a pack history of \< 10 pack years. Number of pack years = (number of cigarettes per day/20) x number of years smoked
• Bodyweight \>= 45kilograms (kg)
• Male OR female of non-reproductive potential Male subjects with female partners of child bearing potential complying with contraception requirements from the time of first dose of study medication until the final follow-up visit: Vasectomy with documentation of azoospermia, male condom plus partner use of one of the following contraceptive options: Contraceptive subdermal implant, Intrauterine device or intrauterine system, Oral contraceptive, either combined or progestogen alone, Injectable progestogen, Contraceptive vaginal ring, Percutaneous contraceptive patches. This is an all-inclusive list of those methods that meet the following GSK definition of highly effective: having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label. For non-product methods (e.g., male sterility), the investigator determines what is consistent and correct use. The GSK definition is based on the definition provided by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception
• A female subject is eligible to participate if she is not pregnant, (as confirmed by a negative \[serum or urine\] human chorionic gonadotrophin \[hCG\] test), not lactating and where the following conditions applies: Non-reproductive potential: defined as pre-menopausal females with one of the following Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause \[refer to laboratory reference ranges for confirmatory levels\]). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment
• Capable of giving signed informed consent

You may not qualify if:

• Alanine transaminase (ALT) \>2xUpper Limit of Normal (ULN) and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Heart rate corrected QT interval (QTc) \> 450 milliseconds (msec) or QTc \> 480 msec in subjects with Bundle Branch Block
• Asthma exacerbation requiring treatment with oral corticosteroids or hospitalization within 3 months prior to screening
• History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 10 years
• Evidence of concurrent respiratory diseases such as pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, allergic bronchopulmonary aspergillosis, cystic fibrosis, bronchopulmonary dysplasia, or other respiratory abnormalities other than asthma
• Other concurrent diseases/abnormalities: A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study
• Respiratory tract infection that is not resolved within 2 weeks prior to screening
• Treatment with intranasal steroid, inhaled corticosteroid (ICS) with or without long-acting beta2-agonist (LABA), and treatment with non-ICS controller asthma medications (i.e., leukotriene modifier, methylxanthines) within 4 weeks prior to screening
• Use of long-acting antihistamines within 7 days' or short-acting antihistamines within 72 hours prior to the screening skin prick test
• Treatment with systemic corticosteroids within 6 weeks prior to screening
• Use of inhaled SABAs as rescue treatment on average for more than 2 days per week
• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of \>14 units for males and females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (\~240 mililiter \[ml\]) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits
• Patient known to be intolerant to salbutamol or albuterol
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Wiesbaden, Hesse, 65187, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

GSK Investigational Site

Manchester, M23 9LT, United Kingdom

Location

Related Publications (1)

• Siddall H, Quint D, Pandya H, Powley W, Shabbir S, Hohlfeld JM, Singh D, Lee L. Intranasal GSK2245035, a Toll-like receptor 7 agonist, does not attenuate the allergen-induced asthmatic response in a randomized, double-blind, placebo-controlled experimental medicine study. PLoS One. 2020 Nov 9;15(11):e0240964. doi: 10.1371/journal.pone.0240964. eCollection 2020.

  PMID: 33166307 BACKGROUND

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 15, 2016
• Study Start: December 5, 2016
• Primary Completion: February 14, 2018
• Study Completion: May 4, 2018
• Last Updated: March 26, 2021
• Results First Posted: May 15, 2019

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

DE (4); GB (2)