Phase II Study to Evaluate the Effect of AZD4604 on Airway Inflammation and Biomarkers in Adults With Asthma

NCT06435273 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: D8210C000052023-510291-32-00
• Study Type: interventional
• Target: 36
• Locations: 5 countries
• Sites: 18

Brief Summary

The purpose of this study is to investigate the effect on airway inflammation and JAK1-associated signalling pathways of AZD4604 compared with placebo in participants with moderate-to-severe asthma. Study details include:

• The study duration for each participant will be approximately 10 weeks.
• The duration of IMP administration will be approximately 4 weeks.

Conditions

Asthma

Keywords

Asthma, Mechanistic Study, Bronchoscopy

Outcome Measures

Primary Outcomes (1)

• Change from baseline to end of investigational medicinal product (IMP) administration in expression of T2 and non-T2, and JAK1-related genes and gene signatures in bronchial brushings

  Gene expression in airway epithelial cells

  4 weeks

Secondary Outcomes (2)

• Change from baseline to end of IMP administration in STAT phosphorylation in bronchial biopsies

  4 weeks

• Change in number of airway cells, including but not limited to inflammatory cells, airway smooth muscle cells, and goblet cells from baseline to end of IMP administration in bronchial biopsies (cells per mm² determined by microscopic evaluation)

  4 weeks

Study Arms (2)

AZD4604

EXPERIMENTAL

AZD4604

Drug: AZD4604

Placebo to AZD4604

PLACEBO COMPARATOR

Placebo to AZD4604

Drug: Placebo to AZD4604

Interventions

AZD4604 DRUG

Janus kinase 1 (JAK1) inhibitor

Also known as: Londamocitinib

AZD4604

Placebo to AZD4604 DRUG

Placebo to AZD4604

Placebo to AZD4604

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented physician-diagnosed asthma ≥ 12 months prior to screening (Visit 1).
• Participants treated with medium-to-high dose ICS in combination with LABA at a stable dose for at least 2 months prior to Visit 1 (the ICS can be contained within an ICS-LABA fixed dose combination product or as separate inhaled products regularly taken together). Treatment with additional asthma controller therapies (eg, long-acting muscarinic antagonist, leukotriene receptor antagonist) at a stable dose ≥ 2 months prior to Visit 1 is allowed. Treatment with maintenance systemic corticosteroids (oral or injectable) is not allowed.
• A documented history of ≥ 1 severe asthma exacerbation within 1 year prior to Visit 1 or ACQ-6 ≥ 1.5 at Visit 1. A severe asthma exacerbation is defined as a worsening of asthma that leads to an inpatient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥ 24 hours) due to asthma.
• Morning pre-BD FEV1 ≥ 60% predicted at Visit 1.
• Able to perform acceptable lung function testing for FEV1 according to American Thoracic Society/ European Respiratory Society (ATS/ERS) 2019 acceptability criteria.
• Able and willing to undertake bronchoscopy. There should be no absolute contra-indications to bronchoscopy as outlined in the bronchoscopy manual.
• Documented evidence of asthma in the 5 years up to or including Visit 1.
• Able and willing to comply with the requirements of the protocol including ability to read, write, be fluent in the translated language of all participant-facing questionnaires used at the study site, and use electronic devices, eg, electronic patient reported outcomes (ePRO) device and spirometer.
• Body weight ≥ 40 kg and body mass index \< 35 kg/m2.
• All females must have a negative serum pregnancy test result at Visit 1.
• Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
• All FOCBP who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control.
• Highly effective birth control methods include:
• Non-hormonalTotal sexual abstinence provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments)
• A vasectomised partner (with confirmed absence of sperm in semen)

You may not qualify if:

• A severe asthma exacerbation within 8 weeks prior to Visit 1.
• History of herpes zoster reactivation (shingles).
• Clinically important pulmonary disease other than asthma, eg, active lung infection, chronic obstructive pulmonary disease (COPD), bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, history or planned lung lobectomy, alpha-1 anti-trypsin deficiency, primary ciliary dyskinesia, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, and hyper-eosinophilic syndrome.
• 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.
• Any clinically significant cardiac or cerebrovascular disease.
• History of venous thromboembolism.
• Current or prior history of alcohol or drug abuse (including marijuana), as judged by the investigator. Positive drug screening result that cannot be justified by participant's medical history and its relevant treatment (over-the-counter product or a valid prescription), or history of or current alcohol or drug abuse (including marijuana and marijuana-containing valid prescriptions), as judged by the investigator.
• History of malignancy other than superficial basal cell carcinoma.
• Treatment with systemic corticosteroid (short-term or maintenance) use within 8 weeks (oral) or 12 weeks (intramuscular) before Visit 1.
• Any immunosuppressive therapy (including hydroxychloroquine, methotrexate, cyclosporine, and tacrolimus) within 12 weeks prior to Visit 1.
• Treatment with marketed biologics including benralizumab, mepolizumab, reslizumab, omalizumab, dupilumab, and tezepelumab within 6 months or 5 half-lives of Visit 1, whichever is longer.
• Inhaled corticosteroid plus fast-acting β2 agonist as a rescue medication (eg, Symbicort, Fostair, or Airsupra Maintenance and Reliever Treatment) is not allowed 30 days prior to Visit 1, during screening, run-in and baseline periods, throughout the treatment period, and preferably until 1 week after the last administration of the IMP.
• Live, attenuated, or mRNA vaccines within 4 weeks of Visit 1.
• Immunoglobulin therapy or blood products within 4 weeks of Visit 1.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (18)

Research Site

Calgary, Alberta, T2N 4Z6, Canada

Location

Research Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Research Site

Montreal, Quebec, H4A 3J1, Canada

Location

Research Site

Québec, Quebec, G1V 4G5, Canada

Location

Research Site

København NV, 2400, Denmark

Location

Research Site

Frankfurt, 60596, Germany

Location

Research Site

Großhansdorf, 22927, Germany

Location

Research Site

Barcelona, 8025, Spain

Location

Research Site

Palma de Mallorca, 07010, Spain

Location

Research Site

Santander, 39008, Spain

Location

Research Site

Birmingham, B9 5SS, United Kingdom

Location

Research Site

Glasgow, G12 0YN, United Kingdom

Location

Research Site

Headington, OX3 9DU, United Kingdom

Location

Research Site

Leicester, LE3 9QP, United Kingdom

Location

Research Site

Liverpool, L7 8YE, United Kingdom

Location

Research Site

London, W12 0HS, United Kingdom

Location

Research Site

Manchester, M23 9QZ, United Kingdom

Location

Research Site

Southampton, SO9 4XY, United Kingdom

Location

Related Publications (1)

• Dosanjh DPS, Darrah E, Jensen TJ, Jevnikar Z, Halvorson A, Cardner M, Hughes R, Grant SS, Platt A, Brightling CE. ARTEMISIA: a mechanistic study of a novel Janus kinase 1 inhibitor to advance molecular understanding and precision medicine in asthma. Respir Res. 2025 Jul 2;26(1):233. doi: 10.1186/s12931-025-03309-3.

  PMID: 40604958 DERIVED

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2024
• First Posted: May 30, 2024
• Study Start: August 5, 2024
• Primary Completion: October 15, 2025
• Study Completion: October 15, 2025
• Last Updated: October 23, 2025

Record last verified: 2025-10

Locations

DK (1); CA (4); GB (8); ES (3); DE (2)