| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| 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 |
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| 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 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA |
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| 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 compared to placebo in adults with asthma who are uncontrolled on medium-to-high 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-to-high 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-to-high dose ICS-LABA |
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| 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. 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 3 months 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 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 50% to 85% (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) |
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| 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. 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. Diagnosis of COVID 19 at screening and prior to randomisation.
7. 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.
8. Significant history of recurrent or ongoing ‘dry eye’, which has been diagnosed and treated with medications prescribed by an Ophthalmologist.
9. Diagnosis of Sjögren’s syndrome.
10. 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.
11. 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 cirrhosis.
12. Evidence of active or untreated latent TB infection (LTBI):
(a) Positive interferon gamma release assay (IGRA, QuantiFERON® TB Gold) test and evidence of symptoms suggestive of active TB.
(b) Positive IGRA, or repeated indeterminate IGRAs, no evidence of active TB and untreated for LTBI, unable to be treated for, or declines treatment of LTBI.
(c) Participants newly diagnosed with LTBI on initial screening could be considered for rescreening if they complete a full course of treatment for LTBI in accordance with recommended treatment guidelines prior to rescreening. In this situation, repeat IGRA test is not required after
completion of treatment for LTBI.
(d) Participants with an indeterminate IGRA should undergo a repeat test and if still indeterminate may be enrolled only after being treated for LTBI
13. 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. |
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| 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 (in clinic)
Part2: Change from baseline in pre bronchodilator FEV1 at Week 4 |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part1: Throughout the study
Part2: Week4 |
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| 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 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 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 (in clinic) 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 (in clinic) |
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| 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 |
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| 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 | No |
| 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
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 48 |
| 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 |
| Ukraine |
| Bulgaria |
| Germany |
| Hungary |
| Ireland |
| Poland |
| Romania |
| Spain |
| United Kingdom |
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| 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
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 10 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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