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

Asthma Clinical Trial

— AJAX  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06020014
• Other study ID #: D8210C00003
• Status: Recruiting
• Phase: Phase 2
• Start date: November 16, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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. A clinical diagnosis of asthma must be documented at least 12 months prior to Screening (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. Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. There are no restrictions on male participants or their female partners

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 of child bearing potential 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 HIV.

10. Current or prior history of alcohol or drug abuse (including marijuana and marijuana containing valid prescriptions), 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 ß2 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. Concurrent enrolment in another interventional clinical study

20. Participant treated with any investigational drug within 4 months or 5 half-lives, whichever is longer, prior to Visit 1.

21. Participants with a known hypersensitivity to AZD4604 or any of the excipients of the product.

22. Abnormal findings identified on physical examination, ECG, or laboratory testing.

23. For female participants only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.

24. Current smokers or participants with smoking history = 10 pack-years.

25. Participants with a known long-term exposure to occupational asbestos, silica, radon, heavy metals, and polycyclic aromatic hydrocarbons.

26. Positive family history of lung cancer in first degree relatives .

27. Positive urine cotinine test or exhaled carbon monoxide test at Visit 1 and at any timepoint throughout the study.

28. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

29. 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.

30. Donation of blood (= 450 mL) within 3 months or donation of plasma within 14 days before Visit 1.

31. Major surgery within 8 weeks prior to Visit 1, or planned inpatient surgery, major dental procedure or hospitalisation during Screening, Treatment, or Follow-up periods.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• AZD4604
AZD4604

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Florida
Argentina	Research Site	La Plata
Argentina	Research Site	Ranelagh
Brazil	Research Site	Barretos
Brazil	Research Site	Blumenau
Brazil	Research Site	Brasilia
Brazil	Research Site	Campinas
Brazil	Research Site	Campinas
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Sao Bernardo do Campo
Brazil	Research Site	Sao Bernardo do Campo
Brazil	Research Site	Sao Jose Do Rio Preto
Bulgaria	Research Site	Burgas
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Denmark	Research Site	Aarhus
Denmark	Research Site	Ålborg
Denmark	Research Site	Hellerup
Denmark	Research Site	Hvidovre
Denmark	Research Site	København NV
Denmark	Research Site	København Ø
Denmark	Research Site	Næstv
Denmark	Research Site	Odense C
Denmark	Research Site	Vejle
France	Research Site	Antony
France	Research Site	Cannes
France	Research Site	Epagny Metz-Tessy
France	Research Site	Libourne Cedex
France	Research Site	Lyon Cedex 04
France	Research Site	Montpellier
France	Research Site	Quimper cedex
France	Research Site	Strasbourg
France	Research Site	VANNES cedex
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Cottbus
Germany	Research Site	Darmstadt
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Koblenz
Germany	Research Site	Mainz
Germany	Research Site	München
Germany	Research Site	Peine
Germany	Research Site	Schwerin
Korea, Republic of	Research Site	Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Malaysia	Research Site	Batu Caves
Malaysia	Research Site	Kajang
Malaysia	Research Site	Kota Bharu
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuantan
Malaysia	Research Site	Melaka
Malaysia	Research Site	Sungai Buloh
Philippines	Research Site	Davao City
Philippines	Research Site	Manadaluyong City
Philippines	Research Site	Pasig
Philippines	Research Site	Quezon City
Philippines	Research Site	Roxas City
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Newton
South Africa	Research Site	Observatory
South Africa	Research Site	Umkomaas
Spain	Research Site	Barcelona
Spain	Research Site	Granada
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Marbella
Spain	Research Site	Santiago de Compostela
Sweden	Research Site	Linköping
Sweden	Research Site	Lund
Sweden	Research Site	Örebro
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Umeå
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan City
Taiwan	Research Site	Yunlin
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khlong Luang
Thailand	Research Site	Khon Kaen
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Thetford
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Asheville	North Carolina
United States	Research Site	Atlanta	Georgia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boerne	Texas
United States	Research Site	Chandler	Arizona
United States	Research Site	Columbus	Ohio
United States	Research Site	Denver	Colorado
United States	Research Site	El Paso	Texas
United States	Research Site	Hammond	Indiana
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Lakeland	Florida
United States	Research Site	Lakewood	Colorado
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lathrup Village	Michigan
United States	Research Site	Madison	Wisconsin
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	New Bedford	Massachusetts
United States	Research Site	New Bern	North Carolina
United States	Research Site	Newport Beach	California
United States	Research Site	North Hollywood	California
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Salisbury	North Carolina
United States	Research Site	Stockton	California
United States	Research Site	Tallahassee	Florida
United States	Research Site	Union City	New Jersey
United States	Research Site	Winston-Salem	North Carolina
Vietnam	Research Site	Da Nang
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city
Vietnam	Research Site	Hochiminh
Vietnam	Research Site	Hue

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Bulgaria,  Denmark,  France,  Germany,  Korea, Republic of,  Malaysia,  Philippines,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first CompEx Asthma event	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.	12 weeks
Secondary	Pre-BD FEV1	Change from baseline in pre-bronchodilator forced expiratory volume in 1 second.	12 weeks
Secondary	CAAT	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.	12 weeks
Secondary	ACQ-6	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.	12 weeks
Secondary	Average morning and average evening PEF	Change from baseline in average morning and evening Peak Expiratory Flow (PEF) measurement.	12 weeks
Secondary	Daily asthma symptom score (total, daytime, and night-time)	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.	12 weeks
Secondary	Time to first CompEx acute worsening event	Time to first CompEx Asthma acute worsening event.	12 weeks
Secondary	CompEx event rate	The number of CompEx Asthma events recorded in the 12-week period.	12 weeks
Secondary	CompEx acute worsening event rate	The number of CompEx Asthma acute worsening events recorded in the 12-week period.	12 weeks