A Safety and Efficacy Study of Intranasal GSK2245035 in Adults With Allergic Asthma

NCT03707678 | Withdrawn Phase 2

• 1 other identifier: 207542
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

GSK2245035 belongs to a novel class of agonist drugs targeted at toll like receptors (TLR). T-helper cell 2 (Th2) driven inflammation is a key patho-physiological mechanism in allergic asthma. The clinical manifestations and inflammatory pathways of allergic asthma are sensitive to corticosteroid therapy. However, GSK2245035 reduces Th2-driven airway inflammation and thereby controls asthma symptoms. This study aims to determine whether intranasal GSK2245035 maintains biological and clinical control of allergic asthma using 'tapering of ICS' study design. This study will assess the efficacy and safety of GSK2245035 in subjects with allergic asthma treated with ICS. This will be a randomised, double-blind (sponsor open), placebo-controlled, parallel group, 8-week study treatment period. The study will consist of a screening period of up to approximately 5 weeks, blinded treatment period of 8 weeks, followed by a follow-up period of 7 weeks. A total of 60 subjects will be included in this study and duration of time for each subject will therefore be 141 days including screening and study ICS dose adjustment period. Diskus® is a registered trademark of GlaxoSmithKline group of companies.

Conditions

Asthma

Keywords

GSK2245035; Allergic asthma; Inhaled corticosteroids; Toll-like receptors

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in fractional exhaled breath nitric oxide (FeNO) level

  FeNO level will be measured to determine efficacy of GSK2245035 in reducing asthma (airway) inflammation. The measurements will be performed using a handheld electronic device. 'Primary Endpoint Visit' (PEPV) will be 1-week post 8th dose. Subjects withdrawn from the study before PEPV because of protocol defined asthma worsening will attend a 'treatment withdrawal visit'.

  Baseline and up to Week 9

Secondary Outcomes (2)

• Number of subjects experiencing worsening of asthma from Baseline to PEPV

  Baseline and up to Week 9

• Time for FeNO to increase by 10 parts per billion (ppb)

  Up to Week 15

Study Arms (2)

Subjects receiving GSK2245035

EXPERIMENTAL

Eligible subjects will be administered 20 nanograms (ng) of GSK2245035 nasal spray solution using a metered Valois VP7 pump (1 spray=10 ng per actuation per nostril) once weekly for 8 weeks. Subjects will also receive tapering doses of FP-DPI 100-500 mcg twice daily during the treatment period. Albuterol/Salbutamol metered dose inhaler (MDI) will be given for symptom relief from screening to the end of the study.

Drug: GSK2245035; Drug: FP-DPI; Drug: Albuterol/Salbutamol; Other: eDairy; Other: ACQ-6

Subjects receiving placebo

PLACEBO COMPARATOR

Eligible subjects will be administered placebo nasal spray solution using a metered Valois VP7 pump (1 spray per actuation per nostril) once weekly for 8 weeks. Subjects will also receive tapering doses of FP-DPI 100-500 mcg twice daily during the treatment period. Albuterol/Salbutamol MDI will be given for symptom relief from screening to the end of the study.

Drug: Placebo; Drug: FP-DPI; Drug: Albuterol/Salbutamol; Other: eDairy; Other: ACQ-6

Interventions

GSK2245035 DRUG

GSK2245035 will be administered weekly once as a nasal spray solution with dosing strength of 10 ng per actuation. GSK2245035 will be available as a saline formulation, preserved with benzalkonium chloride and disodium edetate in an amber glass bottle fitted with a screw-fit atomizing pump.

Subjects receiving GSK2245035

Placebo DRUG

Placebo will be administered weekly once as a nasal spray solution. Placebo will be available as a saline formulation, preserved with benzalkonium chloride and disodium edetate in an amber glass bottle fitted with a screw-fit atomizing pump.

Subjects receiving placebo

FP-DPI DRUG

FP will be administered using Diskus inhaler with dosing strengths of 500, 250, 100, 50 µg twice daily per actuation.

Subjects receiving GSK2245035; Subjects receiving placebo

Albuterol/Salbutamol DRUG

Albuterol/Salbutamol MDI will be administered for symptom relief from screening to the end of the study.

Subjects receiving GSK2245035; Subjects receiving placebo

eDairy OTHER

Subjects will record all the alerts indicative of worsening of asthma in eDairy.

Subjects receiving GSK2245035; Subjects receiving placebo

ACQ-6 OTHER

ACQ-6 will include six questions which enquire about the frequency and/or severity of symptoms. The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/limitation) scale.

Subjects receiving GSK2245035; Subjects receiving 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.
• Physician confirmed diagnosis of asthma for at least 6 months prior to screening.
• Asthma therapy with inhaled corticosteroids (fluticasone propionate dry powder inhaler \[FP-DPI\] \>=100 micrograms (mcg), or equivalent, total daily dose) \>=3 months (at time screening visit 1 \[SV1\]).
• Body weight \>= 45 kilograms (kg).
• Male or female of non-reproductive potential. A male subject must agree to use a highly effective contraception during the treatment period and at least from the time of first dose of study medication until the final follow-up visit and refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WOCBP).
• Capable of giving signed informed consent.

You may not qualify if:

• Current smokers or former smokers with a smoking history \>=10 pack years.
• Clinically significant abnormal laboratory result (Chemistry, Hematology and Urinalysis) at SV1.
• 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 percent).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Clinically significant and abnormal electrocardiogram (ECG) at screening visit 1.
• Heart rate corrected QT interval (QTc) \> 450 milliseconds (msec) or QTc \> 480 msec in subject with Bundle Branch Block.
• Subjects with a diagnosis of malignancy or in the process of investigation for a malignancy.
• Subjects on oral corticosteroid therapy.
• Subjects who have received treatment with allergen immunotherapy (in the last 2 years), anti-immunoglobulin E (IgE) or anti interleukin 5 (IL5) or anti IL13 antibodies or immunosuppressive agents (example given \[e.g.\] methotrexate, azothioprine, cyclosporine) within the past 6 months.
• A pre-bronchodilator forced expiratory volume in 1 second (FEV1) \< 50 percent predicted of normal value.
• Occupational asthma due to low molecular weight chemicals.
• Asthma exacerbation requiring treatment with systemic 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 hypercapnia, respiratory arrest or hypoxic seizures within the last 10 years.
• Evidence of concurrent respiratory diseases such as pneumonia, tuberculosis, pneumothorax, atelectasis, pulmonary fibrotic disease, allergic bronchopulmonary aspergillosis, cystic fibrosis, bronchopulmonary dysplasia, or other respiratory abnormalities other than asthma.
• Respiratory tract infection that is not resolved within 2 weeks prior to screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Asthma

Interventions

GSK2245035; Albuterol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double blind study where the investigators and subjects will be blinded and sponsor remains unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This will be a parallel-group study. Subjects will be randomized in 1:1 ratio to receive GSK2245035 or placebo once weekly for 8 weeks.

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 16, 2018
• Study Start: January 21, 2019
• Primary Completion: December 23, 2019
• Study Completion: December 23, 2019
• Last Updated: October 16, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• 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.