Phase 2
N=36
Effect of the GSK2245035 on the Allergen-induced Asthmatic Response
Asthma
Bottom Line
View on ClinicalTrials.gov: NCT02833974 ↗Enrolled (actual)
36
Serious AEs
0.0%
Results posted
May 2019
Primary outcome: Primary: 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 — -1.107; -0.885 Liters
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GSK2245035 Nasal Spray Solution (Drug); Placebo Nasal Spray Solution (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Feb 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
-1.107; -0.885 | — |
| PRIMARY LAR: Absolute Change From Saline in Weighted Mean FEV1 Between 4-10 Hours Following Allergen Challenge One Week After Treatment |
-0.546; -0.576 | — |
| SECONDARY Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hours Following Allergen Challenge One Week After Treatment |
-1.246; -1.096 | — |
| SECONDARY EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hours Following Allergen Challenge One Week After Treatment. |
-0.604; -0.587 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
10; 21; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Peak Expiratory Flow (PEF) |
0; 0 | — |
| SECONDARY Number of Participants Receiving Rescue Medication |
1; 2 | — |
| SECONDARY Number of Participants With Hematology Values of Potential Clinical Concern |
9; 14 | — |
| SECONDARY Number of Participants With Clinical Chemistry Values of Potential Clinical Concern |
1; 2 | — |
| SECONDARY Number of Participants With Abnormal Urine Analysis Findings |
0; 0 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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 = 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
Exclusion Criteria
- 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 450 milliseconds (msec) or QTc > 480 msec in subj
Data sourced from ClinicalTrials.gov (NCT02833974). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.