Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma
- Registration Number
- NCT05251259
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a randomised, placebo-controlled, double-blind study to assess the efficacy and safety of Atuliflapon administered once daily over a 12-week treatment period to adult participants with moderate to severe uncontrolled asthma.
- Detailed Description
The study will enroll participants with moderate to severe uncontrolled asthma who are on low-dose inhaled corticosteroid (ICS) - a long-acting beta-agonist (LABA) or medium-to-high-dose ICS with or without LABA background treatment.
The study will be initiated by Lead-in pharmacokinetics (PK) cohort in asthma participants. Participant will be randomised globally, including participants in Lead-in PK cohort (2 arms) and in Part 1 of the study (2 arms).
In the Lead-in PK cohort, participants will be randomised to Atuliflapon or placebo (recruitment completed).
In Part 1 of the study, participants will be stratified by geographical region, and grouped based on high or low levels of biomarker at screening (Visit 1).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 666
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lead-in PK cohort (Placebo) Placebo Randomised participants will receive matching placebo to Atuliflapon in Lead-in PK cohort of the study. Part 1 (Atuliflapon) Atuliflapon Randomised participants will receive Atuliflapon in Part 1 of the study. Part 1 (Placebo) Placebo Randomised participants will receive matching placebo to Atuliflapon in Part 1 of the study. Lead-in PK cohort (Atuliflapon) Atuliflapon Randomised participants will receive Atuliflapon in Lead-in PK period of the study.
- Primary Outcome Measures
Name Time Method Time to first CompEx Asthma event Baseline up to Week 12 The clinical efficacy of Atuliflapon Dose A will be assessed by calculating a Hazard Ratio between the treatment arms, Atuliflapon Dose A vs. placebo, in a selected population (based on biomarker level).
CompEx Asthma, a novel composite endpoint for exacerbations, captures asthma-worsening episodes based on a combination of diary events (worsening in daily peak expiratory flow (PEF), asthma symptoms and reliever medication use) plus severe asthma exacerbation events.
- Secondary Outcome Measures
Name Time Method Time to first CompEx Asthma event (Composite endpoint for Exacerbations) From Baseline up to Week 12 The clinical efficacy of Atuliflapon Dose A will be assessed using a predetermined biomarker threshold using the Hazard Ratio of Atuliflapon Dose A vs. placebo, in all participants (with both high and low levels of biomarker) randomised to either placebo or Atuliflapon arms.
Change from baseline in Pre-bronchodilator in forced expiratory volume in 1 second (FEV1) From Baseline up to Week 2, Week 4 and Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo (based on biomarker) of adult participants with moderate-to-severe uncontrolled asthma.
Change from baseline in St. George's Respiratory Questionnaire From Baseline up to Week 4 and Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma.
The St. George's Respiratory Questionnaire (SGRQ) is a 50-item PRO (Patient Reported Outcomes) instrument to measure the health status of participants with airway obstruction diseases. The questionnaire is divided into two parts: part one consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yields a total score and three domain scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status.Change from baseline in Asthma Control Questionnaire 6 From Baseline up to Week 4, Week 8, Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma.
The Asthma Control Questionnaire 6 (ACQ-6) has 6 questions (the top scoring 5 symptoms and daily rescue bronchodilator use). The symptom and bronchodilator use questions on a 7-point scale (0 = no impairment, 6 = maximum impairment). Score 0 means totally controlled and 6 reflects severely uncontrolled.Change from baseline in average morning and evening Peak Expiratory Flow Measurement From Baseline up to Week 4, Week 8, Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma.
Change from baseline in Daily asthma symptom score (total, daytime, and night-time) From Baseline up to Week 4, Week 8, Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma.
Asthma symptom scores during night-time and day-time will be assessed by the participant each morning and evening according to the following scoring system: (0) You have no asthma symptoms; (1): You are aware of your asthma symptoms, but you can easily tolerate the symptoms; (2): Your asthma is causing you enough discomfort to cause problems with normal activities (or with sleep); (3): You are unable to do your normal activities (or to sleep) because of your asthma. Here, low score reflects no asthma symptoms and high score suggests severe or frequent symptoms.Time to first severe asthma exacerbation From Baseline up to Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma. The summary measure for the time-to-event endpoints is being presented as a hazard ratio.
Event status (CompEx Asthma event yes/no) From Baseline up to Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma. The summary measure for the time-to-event endpoints is being presented as a hazard ratio.
Lead-in PK: Area under the curve (AUC) Day 1 and Day 15 PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort.
Lead-in PK: Maximum (or peak) serum concentration (Cmax) Day 1 and Day 15 PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort.
Lead-in PK cohort: Pre-dose trough concentration (Ctrough) Day 15 PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort.
Part 1 Cohort: Atuliflapon plasma concentrations in all participants, pre-dose samples Baseline, Week 4 and Week 12 The pre-dose plasma concentrations of Atuliflapon will be summarised.
Number of participants with adverse events (AEs) Baseline up to Week 12 The safety and tolerability of Atuliflapon will be assessed in adult participants with moderate-to-severe uncontrolled asthma.
Trial Locations
- Locations (1)
Research Site
🇬🇧Watford, United Kingdom