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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

26 Sep 2024 → 28 Oct 2025

Decision date (initial)

2024-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-506000-50-00

ClinicalTrials.gov

NCT06020014

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the clinical efficacy of AZD4604 1.4 mg BID as compared to placebo in adult participants with moderate-to-severe uncontrolled asthma.

Secondary objectives 3

1. To evaluate the effect of AZD4604 on airway inflammation as measured by FeNO.
2. To evaluate the effect of AZD4604 1.4 mg BID on cough as compared to placebo in adult participants with moderate-to-severe uncontrolled asthma.
3. To evaluate the PK of AZD4604 in all participants after 4 weeks and 12 weeks dosing.

Conditions and MedDRA coding

Adult Patients with Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 18 to 80 years of age inclusive, at the time of signing the informed consent.
2. Treatment with additional asthma controller therapies (LAMA, LTRA) at a stable dose for ≥ 28 days prior to Visit 1 is allowed.
3. Documented history of ≥ 1 severe asthma exacerbation within 1 year prior to Visit 1.
4. Morning pre-BD FEV1 ≥ 40% predicted at Visit 1 and Visit 3 (pre-randomisation).
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.
8. Able and willing to comply with the requirements of the CSP including ability to read, write, be fluent in the translated language of all participants facing questionnaires used at the study site, and use electronic devices, eg, ePRO device and spirometer
9. Body weight of ≥ 40 kg and body mass index of < 35 kg/m2
10. Male and/or female, 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 ≥ 40% (pre-randomisation) 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 FOCBP or female participants on HRT, a negative urine pregnancy test prior to administration of IMP (randomisation).

Exclusion criteria 30

1. A severe asthma exacerbation within 8 weeks prior to randomisation
2. Current or prior history of alcohol or drug abuse (including marijuana), as judged by the investigator
3. History of malignancy other than superficial basal cell carcinoma
4. Treatment with systemic corticosteroid within 4 weeks (oral) or 8 weeks (intramuscular) before Visit 1
5. Any immunosuppressive therapy within 12 weeks prior to Visit 1
6. Treatment with marketed biologics within 6 months of Visit 1 or 5 half-lives, whichever is longer
7. Inhaled corticosteroid plus fast-acting β2 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
8. Live, attenuated, or mRNA vaccines within 4 weeks of Visit
9. Immunoglobulin or blood products within 4 weeks of Visit 1
10. 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
11. Concurrent enrolment in another interventional clinical study 1.
12. History of herpes zoster reactivation
13. Participants with a known hypersensitivity to AZD4604 or any of the excipients of the product
14. Abnormal findings identified on physical examination, ECG, or laboratory testing
15. For female participants only – currently pregnant (confirmed with positive pregnancy test) or breast-feeding
16. Current smokers or participants with smoking history ≥ 10 pack-years
17. Participants with a known long-term exposure to occupational asbestos, silica, radon, heavy metals, and polycyclic aromatic hydrocarbons
18. Positive family history of lung cancer,in first degree relatives (mother, father, sisters, brothers and children).
19. Positive urine cotinine test or exhaled carbon monoxide test at Visit 1 and at any timepoint throughout the study
20. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
21. 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
22. Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1
23. Participants with a significant COVID-19 illness within 6 months of enrollment
24. Clinically important pulmonary disease other than asthma
25. 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
26. Any clinically significant cardiac or cerebrovascular disease
27. History of venous thromboembolism
28. 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
29. 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.
30. Participant treated with any investigational drug within 4 months (or 5 half-lives,whichever is longer) prior to Visit 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first CompEx (composite endpoint for exacerbation) event

Secondary endpoints 5

1. Change from baseline in: 1 Pre-BD FEV1 at Week 4 and Week 12
2. CAAT at Week 4 and Week 12
3. ACQ-6 at Week 4 and Week 12
4. Average morning and average evening PEF at Week 4 and Week 12, and average over the 12-week Treatment period
5. Daily asthma symptom score (total, daytime, and night-time) at Week 4 and Week 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

Astrazeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

Astrazeneca Clinical Study Information Center

Locations

7 EU/EEA countries · 42 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 59 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications