Efficacy and Safety of Three Inhaled Dose Levels of AZD1402 Twice Daily for Four Weeks in Adults with Asthma on Medium Dose Inhaled Corticosteroids

Phase 1

• Conditions: Asthma; MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2020-002828-37-ES
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-05
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 405

Inclusion Criteria

1. Participants 18 to 75 years (inclusive) of age, at the time of signing the informed consent at Visit 1.
2. Participants who have a documented clinical diagnosis of asthma for = 12 months before Visit 1.
3. Participants who are able to perform acceptable pulmonary function testing for FEV1 according to ATS/ERS acceptability criteria.
4. Participants who are able to demonstrate the ability to use the study inhalation device properly (at Visit 2).
5. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Part I
6. Documented treatment with medium dose ICS with LABA for at least 6 months prior to Screening (Visit 1) (ICS equivalent of budesonide dry powder formulation > 400 to 800 µg/day).
7. ICS and LABA must be on stable dose for at least 3 months prior to Visit 1 and may be contained in a combination product or separate inhalers.
8. No asthma exacerbations in last 12 months requiring oral or IV steroids or hospitalisation/ emergency room visit due to asthma.
9. Pre bronchodilator FEV1 = 70% predicted at Screening (Visit 1) and start of Run-in (Visit 2). Prior to spirometry, the following medication withhold periods should be observed:
(a) SABA for at least 6 hours.
(b) Twice daily LABA-containing therapies for at least 12 hours.
(c) Once daily LABA-containing therapies for at least 24 hours
10. Asthma Control Questionnaire 6 score of = 1.0 at Screening (Visit 1) and start of Run-in (Visit 2)

Part 2
11. Demonstration of reversibility to inhaled bronchodilators at Visit 1 (a = 12% and = 200 mL improvement in FEV1 after administration of 4 puffs of salbutamol/albuterol). Prior to spirometry the following medication withhold periods should be observed:
(a)SABA and SAMA for at least 6 hours.
(b)Twice daily LABA and/or LAMA-containing therapies for at least 12 hours.
(c)Once daily LABA and/or LAMA-containing therapies for at least 24 hours.
(d) LTRA for at least 24 hours.
(e)Twice daily theophyllines for at least 12 hours.
(f)Once daily theophyllines for at least 24 hours.
12. Documented treatment with medium dose ICS-LABA for at least 12 months prior to Screening (Visit 1) (ICS equivalent of budesonide dry powder formulation > 400 to 800 µg/day). The ICS must be contained within an ICS-LABA combination product.
13. If on asthma maintenance controller medications in addition to ICS-LABA, the dose of the additional controller medications (eg, leukotriene receptor inhibitors, theophylline, LAMA, and chromones) must be stable for at least 3 months prior to Visit 1.
14. Have had at least one severe asthma exacerbation (defined as a worsening of asthma requiring treatment with systemic corticosteroids for 3 days or more, or hospitalisation) in the 12 months prior to Visit 1.
15. Pre bronchodilator FEV1 of 60% to 80% (inclusive) predicted at Screening (Visit 1) and start of Run-in (Visit 2).
16. Blood eosinophil count of = 150 cells/µL and FeNO = 25 ppb at Screening (Visit 1).
17. Asthma Control Questionnaire 6 score = 1.5 at Screening (Visit 1)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 324
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 81

Exclusion Criteria

1. Known or suspected hypersensitivity including anaphylaxis/anaphylactoid reaction following any biologic therapy, or known history of drug hypersensitivity to any component of the study intervention formulation.
2. Clinically important pulmonary disease other than asthma (eg, active lung infection, COPD, bronchiectasis, idiopathic pulmonary fibrosis, cystic fibrosis, lung cancer, alpha-1 antitrypsin deficiency, allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts).
3. History or clinical suspicion of any clinically relevant or active disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant’s ability to participate in the study, or any other safety concerns in the opinion of the Investigator.
4. Participants with a positive diagnostic nucleic acid test (using PCR) for SARS-CoV-2, the virus responsible for COVID-19 prior to Run-in and randomisation.
5. History of cancer within the last 10 years (20 years for breast cancer) except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured. Any history of lymphoma or lung cancer is strictly exclusionary.
6. Significant history of recurrent or ongoing ‘dry eye’, which has been diagnosed and treated with medications prescribed by an Ophthalmologist.
7. Diagnosis of Sjögren’s syndrome.
8. High risk of infection suggesting abnormal immune function, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), despite infection resolution; or unusually frequent, recurrent or prolonged infections, per Investigator’s judgment.
9. History of, or known significant infection or positivity at Visit 1, including hepatitis B or C, HIV, TB (ie, positive result for IGRA, QuantiFERON® TB-Gold), that may put the participant at risk during participation in the study. Participants with an indeterminate IGRA should undergo repeat testing and may only be enrolled after subsequent negative IGRA.
10. Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to Screening and during Run-in, as determined by the Investigator.
11. Clinically significant upper respiratory tract infection at screening, as determined by the Investigator.
12. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained, that has not been treated with, or has failed to respond to standard of care therapy.
13. Receipt of COVID-19 vaccine (vaccine or booster dose) within 30 days prior to randomisation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified