Efficacy and Safety of Inhaled AZD1402 administered Twice Daily for Four Weeks in Adults with Asthma on Medium-to-High Dose Inhaled Corticosteroids
- Conditions
- MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]Asthma
- Registration Number
- EUCTR2020-002828-37-DE
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 210
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, during Screening and Run in Periods 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. Documented evidence of asthma as demonstrated by any of the following:
(a) Post-BD reversibility of FEV1 = 12% and = 200 mL within 5 years prior to Visit 1, or at Visit 1, or
(b) PEF average daily variability > 10% over a 2 week period within 5 years prior to Visit 1, or
(c) Variability of FEV1 = 12% and = 200 mL between any two clinical visits within 5 years prior to Visit 1, or
(d) Positive bronchial challenge test within 5 years prior to Visit 1. 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 standardized hyperventilation, hypertonic saline or mannitol challenge,
or
(e) Positive exercise test within 5 years prior to Visit 1. A positive test is defined as a fall in FEV1 of > 10% and > 200 mL from pre-challenge.
12. Documented treatment with medium-to-high dose ICS-LABA for at least 6 months prior to Screening (Visit 1) (ICS equivalent of budesonide dry powder formulation > 400 µg/day). ICS and LABA must be on a
stable dose for at least 4 weeks prior to Visit 1, during Screening and
Run in Periods.
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 4 weeks prior to Visit 1, during Screening and Run in Periods.
14. Pre bronchodilator FEV1 of 50% to 85% (inclusive) predicted at Screening (Visit 1) and start of Run-in (Visit 2).
15. Blood eosinophil count of = 150 cells/µL and FeNO = 25 ppb at Screening (Visit 1).
16. 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 195
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
1. Women who are pregnant or breastfeeding, or who are planning to
become pregnant during the study.
2. 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.
3. Evidence of any active clinically important pulmonary disease, other than asthma, within 5 years at screening (eg, active lung infection, COPD, bronchiectasis, idiopathic pulmonary fibrosis, cystic fibrosis, lung cancer, alpha-1 antitrypsin deficiency, etc.).
4. History of pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis).
5. 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.
6. History of severe COVID-19 infection requiring hospitalisation within the last 12 months or clinical history compatible with long COVID (symptoms beyond 12 weeks of acute infection).
7. Confirmed symptomatic COVID-19 infection during Screening, Run-in or prior to randomisation. Participants can be rescreened once recovered if infection is not severe. Participants who are asymptomatic with a positive COVID-19 test could continue in Screening if a repeat test done according to applicable local guidelines is negative within the screening window.
8. Current malignancy or history of malignancy, except for:
(a) Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date of informed consent, and assent when applicable, was obtained.
(b) Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date of informed consent.
9. Significant history of recurrent or ongoing 'dry eye', which has been diagnosed and treated with medications prescribed by an Ophthalmologist.
10. Diagnosis of Sjögren's syndrome.
11. 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.
12. History of, or known significant infection or positivity at Visit 1, Screening Period, including hepatitis B or C, or HIV, that may put the participant at risk during participation in the study. Participants with positive anti HBsAg test, a negative HBsAg test and a negative hepatitis B core total test at Screening may be included into the study if they have a positive hepatitis B vaccination history. Participants where the interpretation of the hepatitis B panel results is inconclusive, may be
included following the confirmation of a negative PCR test. Participants who test positive for anti-hepatitis C antibody may be enrolled if their hepatitis C virus RNA test result is negative in the absence of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method