Study to Assess the Effectiveness and Safety of AZD4604 in Adult Patients with Uncontrolled Moderate-to-Severe Asthma – The AJAX Study

Phase 2

• Conditions: Health Condition 1: J455- Severe persistent asthma

• Registration Number: CTRI/2024/04/065120
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

Age

1. Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.

Type of Participant and Disease Characteristics

2. Participants treated with medium-high dose ICS (as per GINA 2022 ICS dose level table in Appendix F) in combination with LABA at a stable dose for at least 3 months prior to Visit 1 (the ICS can be contained within an ICS-LABA fixed dose combination product).

Treatment with additional asthma controller therapies (eg, LAMA, LTRA) at a stable dose = 3 months prior to Visit 1 is allowed. Treatment with maintenance systemic corticosteroids (oral or injectable) is not allowed (see Section 5.2, Exclusion Criterion 12).

3. A documented history of = 1 severe asthma exacerbation within 1 year prior to Visit 1. A severe asthma exacerbation is defined as a worsening of asthma that leads to any of the following:

Use of systemic corticosteroids for at least 3 consecutive days to treat symptoms of asthma worsening (a single depo-injectable dose of corticosteroids will be considered equivalent to a 3-day bolus/burst of systemic corticosteroids).

An emergency room visit (defined as evaluation and treatment for < 24 hours in an emergency department) due to asthma that required systemic corticosteroids (as per the above).

An inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for = 24 hours) due to asthma.

Acceptable documentation of a severe asthma exacerbation in this protocol is:

Documented prescription of systemic corticosteroids for at least 3 days to treat asthma worsening (a single depo-injectable dose of corticosteroids will be considered equivalent to 3-day bolus/burst of systemic corticosteroids). In participants with an established self-management plan, documented filling of a prescription will be considered adequate.

Clinic visit or consultation (primary or specialized HCP) notes providing evidence of =1 exacerbation in the previous 12 months prior to enrolment.

Emergency room/hospital records that the participant attended an emergency room visit (defined as evaluation and treatment for < 24 hours in an emergency department) due to asthma that required systemic corticosteroids (as per the above).

Discharge summaries from hospital, emergency room or urgent care facility indicating that a participant was hospitalised (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for 24 hours) due to asthma

4.Morning pre-BD FEV1 between = 40% and = 90% predicted at Visit 1 and Visit 3 (pre-randomisation).

5.Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria.

6.Documented evidence of asthma as demonstrated by any of the following in the 10 years up to or including Visit 1:

Post-BD reversibility of FEV1 = 12% and = 200 mL, or

Average daily variability of PEF > 10% over a 2-week period, or

Variability of FEV1 > 12% and 200 mL between any 2 clinical visits, or

Positive bronchial challenge test (a positive test is defined as a fall in FEV1 from pre-challenge of = 20% with standard doses of methacholine or histamine, or = 15% with standardised hyperventilation, hypertonic saline, or mannitol challenge), or

Positive exercise challenge test (a positive test is d

Exclusion Criteria

Medical Conditions

1. A severe asthma exacerbation within 8 weeks of prior to randomisation. (For definition of severe exacerbation see Section 5.1, Inclusion Criterion 3).

2. History of herpes zoster reactivation eg, shingles

Participants with a significant COVID-19 illness within 6 months of enrolment:

Participants with a diagnosis of COVID-19 pneumonia based on radiological assessment.

Participants with a diagnosis of COVID-19 requiring hospitalisation and/or oxygen supplementation therapy.

4. Clinically important pulmonary disease other than asthma eg, active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, history or planned lung lobectomy, alpha-1 anti-trypsin deficiency, primary ciliary dyskinesia, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis and hyper-eosinophilic syndrome.

5. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could:

affect the safety of the participant throughout the study,

influence the findings of the study or the interpretation, or

impede the participant s ability to complete the entire duration of study.

6. Any clinically significant cardiac or cerebrovascular disease:

Unstable angina, acute coronary syndrome (acute myocardial infarction, unstable angina), coronary intervention with percutaneous coronary intervention/coronary artery bypass surgery or stroke within 6 months of Visit 1.

Heart failure, New York Heart Association, Classes II to IV.

Systemic hypertension, except if well-controlled using 2 or fewer medications and stable for at least 6 months.

Untreated high degree atrioventricular block (second – third degree atrioventricular block)/significant sinus node dysfunction/pause or therapy requiring tachyarrhythmia. Participants with atrial fibrillation or flutter and optimally controlled ventricular rate at resting < 100 bpm might be included as judged by the investigator.

History or family history of long QT-syndrome or sudden cardiac death with age < 40 years old.

History of QT prolongation associated with other medications that required discontinuation of that medication.

Hypertrophic cardiomyopathy or clinically significant valvular heart disease.

Pulmonary arterial hypertension, either idiopathic or due to connective tissue or thromboembolic disease.

History of venous thromboembolism.

8. Participants who, as judged by the investigator, have evidence of active TB, either treated or untreated, or latent TB without completion of an appropriate course of treatment or appropriate ongoing prophylactic treatment. Evaluation will be according to the local standard of care as determined by local guidelines and may consist of history and physical examinations, chest X-ray, or TB test (eg, purified protein derivative or QuantiFERON test).

9. Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or HIV. Any of the following would exclude the participant from the study:

Participants pos

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the clinical efficacy of AZD4604 1.4 mg BID as compared to placebo in adult participants with moderate-to-severe uncontrolled asthma <br/ ><br>Timepoint: Endpoint: Time to first CompEx event <br/ ><br>Strategy of intercurrent eventsa: Intercurrent events are events occurring after treatment initiation that affect either the measurement or interpretation of the summary measure associated with the clinical question of interest. <br/ ><br> <br/ ><br>Primary estimand: While on treatment – if an intercurrent event occurs before first CompEx event, the participant will be censored at the time of intercurrent event. <br/ ><br> <br/ ><br>