| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part1: To evaluate the safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA
Part2: To investigate the efficacy of inhaled AZD1402 at different dose levels compared to placebo in adults with asthma who are uncontrolled on medium dose ICS-LABA |
|
| E.2.2 | Secondary objectives of the trial |
Part1: To investigate the PK profile and immunogenicity of AZD1402, and associated effects on safety
Part2:
1. To further investigate the efficacy of AZD1402 at different dose levels compared to placebo in adults with asthma who are uncontrolled on medium dose ICS-LABA
2. To investigate the effect of AZD1402 compared to placebo on airway inflammation in adults with asthma who are uncontrolled on medium dose ICS LABA
3. To investigate the PK profile and immunogenicity of AZD1402, and associated effects on safety
4. To evaluate the safety and tolerability of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium dose ICS-LABA |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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, 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. 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). ICS and LABA must be on a
stable dose for at least 3 months prior to Visit 1, during Screening and
Run in Periods. The ICS must be contained within an ICS-LABA
combination product from Visit 1 and for the duration of the study.
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, during Screening and Run in Periods.
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 3 years 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) |
|
| E.4 | Principal exclusion criteria |
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. 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).
4. 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.
5. 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.
6. 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.
7. Significant history of recurrent or ongoing ‘dry eye’, which has been diagnosed and treated with medications prescribed by an Ophthalmologist.
8. Diagnosis of Sjögren’s syndrome.
9. 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.
10. History of, or known significant infection or positivity at Visit 1,
Screening Period, 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 positive anti HBsAg
test, HBsAg and negative hepatitis B core total 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 with an indeterminate IGRA should
undergo repeat testing and may only be randomised after subsequent
negative IGRA.
11. Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to Screening and during Run-in, as determined by the Investigator.
12. Clinically significant upper respiratory tract infection at Screening and during Run-in, as determined by the Investigator.
13. 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.
14. Receipt of COVID-19 vaccine (vaccine or booster dose) within 30 days prior to randomisation. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part1:
• Adverse events / AESIs / SAEs with a particular focus on infection, eosinophilia, and hypersensitivity-like events
• Vital signs
• Changes in clinical chemistry, haematology and coagulation parameters
• Immuno-biomarkers (including but not limited to cytokines, CRP, immunoglobulins including IgE)
• ECGs
• FEV1
• FeNO
Part2: Change from baseline in pre bronchodilator FEV1 at Week 4 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part1: Throughout the study
Part2: Week4 |
|
| E.5.2 | Secondary end point(s) |
Part1:
• PK parameters (full profile in all participants)
• ADAs
Part2:
1. • Change from baseline in pre bronchodilator FEV1 average over the 4 week Treatment Period
• Change from baseline in post bronchodilator FEV1 average over the 4 week Treatment Period
• Change from baseline in ACQ-6 at Week 4 and average over the Treatment Period
• Proportion of participants with a decrease in ACQ 6 score of ≥ 0.5 from baseline to Week 4
• Change from baseline in SGRQ score to Week 4
• Change from baseline in average morning PEF over the Treatment Period
• Change from baseline in average evening PEF over the Treatment Period
• Change from baseline in daily average asthma symptom score (AM/PM) over the Treatment Period
2. Change from baseline in FeNO at Week 4 and average over the Treatment Period
3. • PK parameters (sparse in all, full profile in a subset of participants in each treatment arm)
• ADAs
4. • Adverse events / AESIs / SAEs with a particular focus on infection, eosinophilia, and hypersensitivity like events
• Vital signs
• Changes in clinical chemistry, haematology, and coagulation parameters
• Immuno-biomarkers (including but not limited to cytokines, CRP, immunoglobulins including IgE)
• ECGs
• FEV1
• FeNO |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part1: Throughout the study
Part2:
1. week 4/ change from baseline over the treatment period
2. week 4, and change from baseline over the treatment period
3. throughout the study
4. throughout the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Korea, Republic of |
| Taiwan |
| Poland |
| Spain |
| Germany |
| Hungary |
| Ukraine |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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