Phase 2a Study to Assess the Efficacy and Safety of AZD4604 in Adult Patients With Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA (AJAX)

• ClinicalTrials.gov Identifier: NCT06020014
• Recruitment Status: Recruiting
• First Posted: August 31, 2023
• Last Update Posted: April 26, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: August 25, 2023
• First Posted Date: August 31, 2023
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: November 16, 2023
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 25, 2023)

Time to first CompEx Asthma event [ Time Frame: 12 weeks ]

CompEx Asthma is a composite surrogate endpoint for exacerbations that captures: - acute worsening events based on a combination of events based on ePRO data (asthma symptoms and rescue medication use), PEF data, and severe asthma exacerbation events.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 25, 2023)

• Pre-BD FEV1 [ Time Frame: 12 weeks ]
  Change from baseline in pre-bronchodilator forced expiratory volume in 1 second.
• CAAT [ Time Frame: 12 weeks ]
  Change from baseline in the Chronic Airways Assessment Test (CAAT). The CAAT is an 8-item patient-reported outcome measure developed to measure health status in patients with asthma and COPD.
• ACQ-6 [ Time Frame: 12 weeks ]
  Change from baseline in the Asthma Control Questionnaire 6 (ACQ-6). The ACQ-6 has 6 questions (regarding asthma symptoms and rescue bronchodilator use). Answering the questions results in a score out of 6. A Score of 0 indicates complete control and 6 reflects severely uncontrolled disease.
• Average morning and average evening PEF [ Time Frame: 12 weeks ]
  Change from baseline in average morning and evening Peak Expiratory Flow (PEF) measurement.
• Daily asthma symptom score (total, daytime, and night-time) [ Time Frame: 12 weeks ]
  Change from baseline in Daily asthma symptom score. Asthma symptoms are assessed (0 to 3 scale) twice daily, once in the morning and once in the evening.
• Time to first CompEx acute worsening event [ Time Frame: 12 weeks ]
  Time to first CompEx Asthma acute worsening event.
• CompEx event rate [ Time Frame: 12 weeks ]
  The number of CompEx Asthma events recorded in the 12-week period.
• CompEx acute worsening event rate [ Time Frame: 12 weeks ]
  The number of CompEx Asthma acute worsening events recorded in the 12-week period.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 2a Study to Assess the Efficacy and Safety of AZD4604 in Adult Patients With Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA
• Official Title: A Phase 2a Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AZD4604 Twice Daily for Twelve Weeks in Adult Patients With Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA
• Brief Summary: This is a Phase 2a, multicentre, randomised, placebo-controlled, double-blind, parallel-group study to evaluate the efficacy, safety and PK of AZD4604 administered BID using a dry-powder inhaler at one dose level over a 12-week Treatment period in adult participants with uncontrolled moderate-to-severe asthma.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Asthma

Intervention

• Drug: AZD4604
  AZD4604
• Other: Placebo
  Placebo

Study Arms

• Experimental: Arm 1
  AZD4604
  Intervention: Drug: AZD4604
• Placebo Comparator: Arm 2
  Placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 25, 2023): 320
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2025
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 18 to 80 years of age inclusive, at the time of signing the informed consent.
2. Treated with medium-high dose ICS in combination with LABA at a stable dose for at least 3 months prior to Visit 1.
3. Documented history of ≥ 1 severe asthma exacerbation within 1 year prior to Visit 1.
4. Morning pre-BD FEV1 between ≥ 40% and ≤ 90% predicted at Visit 1 and Visit 3.
5. Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria.
6. Documented evidence of asthma in the 10 years up to or including Visit 1.
7. An ACQ-6 score ≥ 1.5 at Visit 1 and at Visit 3.

9. Body weight of ≥ 40 kg and body mass index of < 35 kg/m2. 10. Male and/or female: Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

At the end of the Run-in period (Visit 3), participants must fulfil the following additional criteria in order to be randomised into the study and enter the Treatment period:

1. Pre-BD FEV1 between ≥ 40% and ≤ 90% predicted.
2. A pre-BD/pre-IMP dose FEV1 at Visit 3 that has not increased or decreased by 20% or more from the pre-BD FEV1 recorded at Visit 1 and at Visit 2.
3. An ACQ-6 score of ≥ 1.5.
4. At least 80% compliance with usual asthma background medication during Run-in period (from Visit 2 to Visit 3) based on the daily asthma ePROs.
5. Minimum 80% compliance with daily eCOAs (electronic Clinical Outcome Assessments) during the Run-in period and during the 14 days preceding Visit 3.
6. For female participants, a negative urine pregnancy test prior to administration of IMP.

Exclusion Criteria:

1. A severe asthma exacerbation within 8 weeks prior to randomisation.
2. History of herpes zoster reactivation.
3. Participants with a significant COVID-19 illness within 6 months of enrolment.
4. Clinically important pulmonary disease other than asthma.

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.
7. History of venous thromboembolism.
8. Participants who, as judged by the investigator, have evidence of active TB, or latent TB without completion of an appropriate course of treatment or appropriate ongoing prophylactic treatment.
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.
10. Current or prior history of alcohol or drug abuse (including marijuana), as judged by the investigator.
11. History of malignancy other than superficial basal cell carcinoma.
12. Treatment with systemic corticosteroid within 4 weeks (oral) or 8 weeks (intramuscular) before Visit 1.
13. Any immunosuppressive therapy within 12 weeks prior to Visit 1.
14. Treatment with marketed biologics within 6 months of Visit 1 or 5 half-lives, whichever is longer.
15. Inhaled corticosteroid plus fast-acting β2 agonist as a reliever is not allowed 15 days prior to Visit 1, during Screening/Run-in and throughout the Treatment period and preferably 1 week after the last dose of IMP.
16. Live, attenuated, or mRNA vaccines within 4 weeks of Visit 1.
17. Immunoglobulin or blood products within 4 weeks of Visit 1.
18. Any immunotherapy within 6 months of Visit 1, except for stable maintenance dose allergen-specific immunotherapy started at least 4 weeks prior to Visit 1 and expected to continue through to the end of the Follow-up period.
19. Participant treated with any investigational drug within 4 months or 5 half-lives, whichever is longer, prior to Visit 1.
20. Participants with a known hypersensitivity to AZD4604 or any of the excipients of the product.
21. Abnormal findings identified on physical examination, ECG, or laboratory testing.
22. For female participants only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
23. Current smokers or participants with smoking history ≥ 10 pack-years.
24. Participants with a known long-term exposure to occupational asbestos, silica, radon, heavy metals, and polycyclic aromatic hydrocarbons.
25. Positive family history of lung cancer.
26. Positive urine cotinine test or exhaled carbon monoxide test at Visit 1 and at any timepoint throughout the study.
27. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
28. Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
29. Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: Argentina, Brazil, Bulgaria, Denmark, France, Germany, Malaysia, Philippines, South Africa, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States, Vietnam

Administrative Information

• NCT Number: NCT06020014
• Other Study ID Numbers: D8210C00003
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: April 2024