AsthmaPhase 2NCT03707678
A Safety and Efficacy Study of Intranasal GSK2245035 in Adults With Allergic Asthma
A Phase 2 study testing GSK2245035, FP-DPI and Albuterol/Salbutamol in people with Asthma, run by GlaxoSmithKline.
Trial 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. 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, FP-DPI and Albuterol/Salbutamol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 21 Jan 2019to 23 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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.
- 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.
Who cannot join
- 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.
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- 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.
- Other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes. Subjects with a known, pre-existing parasitic infestation within 6 months prior to screening.
- A current or past diagnosis of an autoimmune disorder such as systemic lupus erythematosus (SLE).
- 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. E.g. Addison's disease hypertension 1 (uncontrolled) aortic aneurysm (clinically significant), peptic ulcer (recent or poorly controlled), Cushing's disease, renal disease, diabetes mellitus (uncontrolled), stroke within 3 months of screening visit 1, thyroid disorder (uncontrolled), hepatic disease tuberculosis (current or untreated).
- History of sensitivity to any of the study medications, including Albuterol/Salbutamol or Albuterol components there of or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- History of hypersensitivity to investigational medicinal product (IMP) or to drugs of similar chemical class (TLR agonists).
- The subject has received an investigational medicinal product within 30 days or, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). Use of a biologic (e.g. monoclonal antibodies) agent for the treatment of asthma in the past 6 months.
- Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
- 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.
- Known positive for Human Immunodeficiency Virus (HIV) antibody.
- Donation or loss of 400 milliliters (mL) or more of blood within 8 weeks prior to initial dosing, or longer if required by local regulation or hemoglobin levels below normal range at screening or where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- 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 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- A history of substance abuse including alcohol.
- Subjects at risk of non-compliance, or unable to comply with the study procedures.
- Subjects who are unable to follow study instructions such as visit schedule, dosing directions, study electronic diary (eDiary) completion, or use of a standard metered dose inhaler. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
About this study
Official title: A Multicentre, Randomised, Placebo-controlled, Double-blind (Sponsor Open), Parallel-group, 8-week Treatment Study Investigating the Efficacy and Safety of Intra-nasal GSK2245035 in Adults With Allergic Asthma Treated With Inhaled Corticosteroids (ICS)
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
- Being tested
- GSK2245035, Placebo, FP-DPI, Albuterol/Salbutamol, eDairy
- Keywords
- GSK2245035, Allergic asthma, Inhaled corticosteroids, Toll-like receptors
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2245035Drug
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.
PlaceboDrug
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.
FP-DPIDrug
FP will be administered using Diskus inhaler with dosing strengths of 500, 250, 100, 50 µg twice daily per actuation.
Albuterol/SalbutamolDrug
Albuterol/Salbutamol MDI will be administered for symptom relief from screening to the end of the study.
eDairyOther
Subjects will record all the alerts indicative of worsening of asthma in eDairy.
ACQ-6Other
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo; Drug: FP-DPI; Drug: Albuterol/Salbutamol; Other: eDairy; Other: ACQ-6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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'.
Measured: Baseline and up to Week 9
Secondary outcomes (2)
Number of subjects experiencing worsening of asthma from Baseline to PEPV
Asthma worsening is defined as one or more of the following: an increase in asthma control questionnaire 6 (ACQ-6) >0.5 from Baseline; a daily asthma symptom score of >=4 for 2 consecutive days; nocturnal awaking(s) due to asthma requiring short-acting beta agonist (SABA) use on 2 consecutive nights; an increase from Baseline of >=4 puffs per day of rescue medication use on 2 consecutive days; >=20 percent reduction in morning peak expiratory flow (PEF) from Baseline and >=20 percent reduction in evening PEF from Baseline for 2 consecutive days; visit to emergency room / department, hospitalization or oral corticosteroid therapy for severe asthma exacerbation.
Measured: Baseline and up to Week 9
Time for FeNO to increase by 10 parts per billion (ppb)
Increase in FeNO by 10 ppb will be calculated from first dose of GSK2245035 or placebo up to the 'study completion visit'.
Measured: Up to Week 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start21 Jan 2019 (estimated)
- Primary completion23 Dec 2019 (estimated)
- Study completion23 Dec 2019 (estimated)
Why it stopped: After careful review of new data on GSK2245035, GlaxoSmithKline has decided to cancel this study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03707678
- Sponsor's protocol ID
- 207542
- Status last verified
- Oct 2018
- First submitted
- 12 Oct 2018
- Last updated
- 16 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Randomised, Placebo-controlled, Double-blind (Sponsor Open), Parallel-group, 8-week Treatment Study Investigating the Efficacy and Safety of Intra-nasal GSK2245035 in Adults With Allergic Asthma Treated With Inhaled Corticosteroids (ICS)
- ClinicalTrials.gov ID
- NCT03707678
- Acronym / sponsor ID
- 207542
- Conditions
- Asthma
- Keywords
- GSK2245035, Allergic asthma, Inhaled corticosteroids, Toll-like receptors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: After careful review of new data on GSK2245035, GlaxoSmithKline has decided to cancel this study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 21 Jan 2019 (estimated)
- Primary completion
- 23 Dec 2019 (estimated)
- Study completion
- 23 Dec 2019 (estimated)
- First posted
- 16 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Subjects receiving GSK2245035 | Experimental | Drug: GSK2245035, Drug: FP-DPI, Drug: Albuterol/Salbutamol, Other: eDairy, Other: ACQ-6Eligible 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. |
| Subjects receiving placebo | Placebo comparator | Drug: Placebo, Drug: FP-DPI, Drug: Albuterol/Salbutamol, Other: eDairy, Other: ACQ-6Eligible 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2245035GSK2245035 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. | Drug | Subjects receiving GSK2245035 |
| PlaceboPlacebo 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. | Drug | Subjects receiving placebo |
| FP-DPIFP will be administered using Diskus inhaler with dosing strengths of 500, 250, 100, 50 µg twice daily per actuation. | Drug | Subjects receiving GSK2245035, Subjects receiving placebo |
| Albuterol/SalbutamolAlbuterol/Salbutamol MDI will be administered for symptom relief from screening to the end of the study. | Drug | Subjects receiving GSK2245035, Subjects receiving placebo |
| eDairySubjects will record all the alerts indicative of worsening of asthma in eDairy. | Other | Subjects receiving GSK2245035, Subjects receiving placebo |
| ACQ-6ACQ-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. | Other | Subjects receiving GSK2245035, Subjects receiving placebo |
Primary outcome
Change from Baseline in fractional exhaled breath nitric oxide (FeNO) level
Time frame: Baseline and up to Week 9
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'.
2 secondary outcomes
Number of subjects experiencing worsening of asthma from Baseline to PEPV
Time frame: Baseline and up to Week 9
Time for FeNO to increase by 10 parts per billion (ppb)
Time frame: Up to Week 15
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK2245035, FP-DPI and Albuterol/Salbutamol in people with Asthma, run by GlaxoSmithKline.
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 6 inclusion and 29 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: withdrawn, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Change from Baseline in fractional exhaled breath nitric oxide (FeNO) level (time frame: Baseline and up to Week 9). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Oct 2018.