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AsthmaPhase 2NCT02833974

Effect of the GSK2245035 on the Allergen-induced Asthmatic Response

A Phase 2 study testing GSK2245035 Nasal Spray Solution in people with Asthma, run by GlaxoSmithKline at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Asthma
What is being tested?
GSK2245035 Nasal Spray Solution
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
36 participants
Where
6 sitesin 2 countries
Study dates
5 Dec 2016to 4 May 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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
  • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment
  • A positive pre-study drug/alcohol screen
  • A positive test for Human Immunodeficiency Virus (HIV) antibody
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
  • Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Germany4 sites

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60596

  • GSK Investigational Site

    Großhansdorf, Schleswig-Holstein, 22927

  • GSK Investigational Site

    Hanover, Lower Saxony, 30625

  • GSK Investigational Site

    Wiesbaden, Hesse, 65187

Other trials in Germany

United Kingdom2 sites

  • GSK Investigational Site

    London, NW10 7EW

  • GSK Investigational Site

    Manchester, M23 9LT

Other trials in United Kingdom

About this study

Official title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, 8-week Treatment Study to Investigate the Safety, Pharmacodynamics, and Effect of the TLR7 Agonist, GSK2245035, on the Allergen-induced Asthmatic Response in Subjects With Mild Allergic Asthma

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
Being tested
GSK2245035 Nasal Spray Solution, Placebo Nasal Spray Solution
Keywords
GSK2245035, TLR7 agonist, allergic asthma, FEV1
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK2245035 Nasal Spray SolutionDrug

    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.

  • Placebo Nasal Spray SolutionDrug

    Nasal Spray Solution as for GSK2245035 without active ingredient.

Study groups in NCT02833974
Study groupRoleWhat they receive
GSK2245035 20 ngExperimentalParticipants 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
Receives: Drug: GSK2245035 Nasal Spray Solution
PlaceboPlacebo comparatorParticipants 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
Receives: Drug: Placebo Nasal Spray Solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Week 9

  2. 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.

    Measured: Week 9

Secondary outcomes (8)

  1. Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 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). Minimum FEV1 over 0-2 hours post-allergen challenge (minimum LAR) is the minimum value of all of the post-saline time points between 0 and 2 hours post-allergen challenge, inclusive of the 0 and 2 hours timepoints. Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value.

    Measured: Week 9

  2. EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 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 0-2 hours post-allergen challenge includes all post-saline time points between 0-2 hours post-allergen challenge, inclusive of 0 and 2 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.

    Measured: Week 9

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

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AEs and SAEs have been reported.

    Measured: Up to Week 20

  4. Number of Participants With Abnormal Peak Expiratory Flow (PEF)

    The PEF is defined as the greatest rate of airflow that can be achieved during forced exhalation beginning with the lungs fully inflated. Participants were instructed to record their PEF readings each morning and evening into the diary card that was provided by the investigator. The minimum and maximum range ranges for PEF were <=205 and >=980 liters per minute.

    Measured: Up to Week 12

  5. Number of Participants Receiving Rescue Medication

    Salbutamol was administered as rescue medication only to participants who experienced serious discomfort. The data below exclude any Salbutamol administered as part of the planned study procedures (for example the Salbutamol administered after the Bronchial Allergen Challenge [BAC] is not counted as a rescue medication).

    Measured: Up to Week 20

  6. Number of Participants With Hematology Values of Potential Clinical Concern

    Blood samples were collected for analysis of hematology parameters. Hematology parameters included hematocrit, hemoglobin, platelet count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and red blood cells (RBC).

    Measured: Up to Week 20

  7. Number of Participants With Clinical Chemistry Values of Potential Clinical Concern

    Blood samples were collected for analysis of clinical chemistry parameters. Clinical chemistry parameters included blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, total and direct bilirubin, albumin, calcium, creatinine, glucose, potassium and sodium.

    Measured: Up to Week 8

  8. Number of Participants With Abnormal Urine Analysis Findings

    Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.

    Measured: Up to Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jul 2016 (estimated)
  2. Study start5 Dec 2016
  3. Primary completion14 Feb 2018
  4. Study completion4 May 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02833974
Sponsor's protocol ID
205540
Other IDs
2015-005645-31, 2015
Status last verified
Feb 2021
First submitted
12 Jul 2016
Last updated
26 Mar 2021
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study is available via the Clinical Study Data Request site.

Publications

  • 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.

    PubMed 33166307

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK2245035 Nasal Spray Solution in people with Asthma, run by GlaxoSmithKline at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Week 9). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02833974, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2021.

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