Clinical trial NCT06702462: A Study to Assess the Potential for Airway Sensitivity Reactions With Propellants HFA-152a (Test) and HFA-134a (Reference) Administered Via Pressurized Inhalers in Adults With Mild Asthma
Official title: A Randomized, Non-inferiority, Double-blind, Controlled, Single-dose, 2-way Cross-over Study to Assess the Potential for Airway Sensitivity Reactions With Propellants HFA-152a (Test) and HFA-134a (Reference) Administered Via Pressurized Metered Dose Inhalers in Adults Aged 18-45 With Mild Asthma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Asthma
Keywords: Asthma
HFA-152a
HFA-134a
pMDI
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-11-25
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the propellants,1 - Difluoroethane \[HFA-152a\] (Test) and 1,1,1,2-Tetrafluoroethane \[HFA-134a\] (Reference) for their potential to cause the airways to tighten when delivered through pressurized metered dose inhalers (pMDI). The rationale for this study is to develop a low carbon footprint alternative propellant, HFA-152a, which will have a lower impact on global warming.


Eligibility criteria: Inclusion Criteria:

Participants are eligible to be included in the study if all the following criteria apply:

* Male or female; females may be of childbearing potential, of nonchildbearing potential, or postmenopausal.
* Participant must be 18 to 45 years of age inclusive, at the time of screening.
* Confirmed diagnosis of asthma: documented, established diagnosis of asthma for at least 6 months.
* Receiving 1 of the following asthma treatments, at a stable dose, for at least 12 weeks prior to the screening visit and is anticipated to remain stable for the duration of the study:

  * As needed short-acting beta-agonists (SABA) only
  * As needed SABA plus low-dose Inhaled corticosteroids (ICS) (defined as 100-250 µg/day fluticasone propionate or equivalent taken whenever SABA is taken).
  * Daily maintenance low-dose ICS, plus as needed SABA or ICS-SABA single inhaler combination therapy
  * Low dose combination single inhaler ICS-formoterol or single inhaler ICS-SABA as needed for symptom relief (and if needed, before exercise)
  * Leukotriene receptor antagonist (LTRAs) in combination with any of the above therapies
* Asthma Control Questionnaire (ACQ)-6 score \<1.5 at screening and Day -1.
* No severe asthma exacerbations within 6 months prior to screening and ≤1 severe exacerbation during the 12 months prior to screening.
* Lung function: subjects with a pre-bronchodilator FEV1 ≥60% predicted at Screening and Day-1.
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

  * Is a Woman of non-childbearing potential (WONCBP) OR
  * Is a Woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of \<1%.
* Female participants must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 28 days before the first dose of study intervention.
* For male participants, no contraceptive measures are required.
* Non-smokers, or previous smokers who have not used any tobacco containing-products or vaping products within 12 months prior to study start, and with a total pack year history of ≤10 pack years.
* The use of marijuana, even with a valid prescription, is prohibited within 12 months prior to study start.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and protocol.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

* A history of life-threatening asthma or asthma that is unstable in the opinion of the investigator.
* Asthma treatment requiring use of biologic agents (e.g. mepolizumab or dupilumab), chronic systemic corticosteroids, or oral controller agents other than LTRAs.
* Respiratory disorders other than asthma; A history of respiratory diseases to include (but not limited to): pneumothorax, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, cystic fibrosis, bronchiectasis, interstitial lung disease, emphysema, chronic obstructive pulmonary disease, tuberculosis and other respiratory abnormalities other than asthma that, in the opinion of the investigator, would put the participant at risk through study participation, or would affect the study analyses if the disease exacerbates and/or requires additional therapy during the study. This includes history of lung cancer and previous thoracic surgery such as lung resection.
* Asthma Exacerbation: Any severe asthma exacerbation within 6 months prior to screening. (Severe asthma exacerbation defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days, or a single depo injection or an in-patient hospitalization or early discontinuation (ED) visit due to asthma that required systemic corticosteroids).
* Biologic/immunosuppressive therapies that can be used for the treatment of respiratory diseases during the 6 months, or 5 half-lives whichever is longer-prior to start of the study.
* Participants undergoing de-sensitization therapy.
* Administration of systemic, oral, or depot corticosteroids for asthma treatment within 12 weeks of Visit 1. Intranasal corticosteroids are permitted if at a stable dose for at least 3 months prior to screening.
* Stable doses (3 months or longer) of the following are permitted:

  * Intranasal corticosteroids
  * Oral anti-histamines

Primary outcomes:
measure: Percentage change from baseline in Forced expiratory volume in 1 second (FEV1) at 15 minutes
timeFrame: Baseline (0 minutes) and at 15 minutes post dose
Secondary outcomes:
measure: Area under the forced expiratory volume in 1 second-time curve from zero to 15 minutes (FEV1 AUC0-15min)
timeFrame: Up to 15 minutes post dose
measure: Percentage change from baseline in FEV1 at 5, 60 and 180 minutes
timeFrame: Baseline (0 minutes) and at 5, 60 and 180 minutes post dose
measure: Percentage change from baseline in FEV1 <-15% at timepoints 5, 15, 60 and 180 minutes
timeFrame: Baseline (0 minutes) and at 5, 15, 60 and 180 minutes post dose
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to approximately 54 days
Other outcomes:
Locations:
city: Marlton
country: United States
facility: GSK Investigational Site
state: New Jersey
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
References: