A study to investigate the effect of AZD6793 in participants with moderate to very severe chronic obstructive pulmonary disease (PRESTO)
Scientific Title of Study
A Multicentre, Parallel-group, Phase IIb, Randomised, Double-blind, Placebo-controlled, 4-Arm, 24-Week Study to Evaluate the Efficacy and Safety of AZD6793 Tablets in Adult Participants with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (PRESTO)
Trial Acronym
PRESTO
Secondary IDs if Any
Secondary ID
Identifier
D7860C00006 Protocol Version 1.0 dated 19 March 2025
Protocol Number
NCT05662033
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Tapankumar M Shah
Designation
Senior Director – Site Management and Monitoring, Biopharmaceuticals R&D
Affiliation
AstraZeneca Pharma India Ltd,
Address
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road
306 Red Rose Msv Vivek Marvel Apts Bangalore KARNATAKA 560064 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Details of Contact Person Scientific Query
Name
Tapankumar M Shah
Designation
Senior Director – Site Management and Monitoring, Biopharmaceuticals R&D
Affiliation
AstraZeneca Pharma India Ltd,
Address
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road
306 Red Rose Msv Vivek Marvel Apts
KARNATAKA 560064 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Details of Contact Person Public Query
Name
Tapankumar M Shah
Designation
Senior Director – Site Management and Monitoring, Biopharmaceuticals R&D
Affiliation
AstraZeneca Pharma India Ltd,
Address
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road
306 Red Rose Msv Vivek Marvel Apts
KARNATAKA 560064 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB, 151 85 Södertälje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Södertälje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road, Bangalore - 560045,
Karnataka
Countries of Recruitment
Argentina Australia Bulgaria Canada Chile China Denmark Germany Greece Hungary India Italy Japan Mexico Peru Portugal Republic of Korea Spain Taiwan Turkey Ukraine United Kingdom United States of America Viet Nam
Formulation: Tablet
Dose strength: 5 mg, 15 mg, and 45 mg
Route: Oral
Frequency: Once daily
Comparator Agent
Placebo
Formulation: Tablet
Dose strength: NA
Route: Oral
Frequency: Once daily
Inclusion Criteria
Age From
40.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Participants are eligible to be included in the study only if all of the following criteria apply
Age
1. Participant must be greater than or equal to 40 years of age at the time of signing the informed consent
2. Documented primary diagnosis of moderate to very severe COPD for at least 12 months prior to enrolment.
3. Pre-BD FEV1 to FVC less than 0.7 at Visit 1 and pre- and post-BD FEV1 to FVC less than 0.7, and post-BD FEV1 greater than or equal to 25 percent to less than 80 percent of predicted normal at Visit 2. If the pre-BD FEV1 to FVC is greater than or equal to 0.7, post-BD spirometry should not be performed.
4. Documented history of greater than or equal to 2 moderate or greater than or equal to 1 severe COPD exacerbations in the 12 months prior to screening (Visit 1). Participants with a documented history of one moderate COPD exacerbation in the 12 months before the screening visit are also eligible (but will be capped at 20 percent of the total sample size). At least one eligible historical COPD exacerbation must have occurred while on the stable maintenance treatment regimen that is required for eligibility. Acceptable documentation is
a. Clinic visit or consultation (primary or specialist healthcare provider) notes or emergency room/hospital records providing evidence of the COPD exacerbation event
b. Documented prescription of systemic corticosteroids of at least 3 days duration (or one injection of depot formulation) and/or antibiotics for treatment of a COPD exacerbation. In participants with an established self-management plan, documented filling of a prescription to replace an above-listed course of therapy will be considered adequate.
c. Discharge summaries from a hospital, emergency room, an urgent care or other equivalent healthcare facility indicating that a participant was hospitalised or treated with systemic corticosteroids or antibiotics for a COPD exacerbation or,
d. Evidence from a pharmacy of filled prescription(s) for systemic corticosteroids (3 days duration or one injection of depot formulation) and/or antibiotics
5. Documented stable regimen of inhaled triple maintenance therapy or inhaled dual maintenance therapy (when triple inhaled therapy is not appropriate) for greater than or equal to 3 months prior to screening (Visit 1). Triple therapy may consist of an appropriate combination of ICS plus LABA plus LAMA. Dual therapy consists of either ICS plus LABA, ICS plus LAMA or inhaled LABA plus LAMA when the treating physician deems the participant unsuitable for triple therapy or ICS (for example, blood eosinophil count less than or equal to 100 cells per millilitre on 2 separate occasions, or on the basis of previous or perceived risk of significant AEs from inhaled ICS-based therapy, such as previous episode(s) of pneumonia or significant oral candidiasis).
Both triple and dual maintenance therapy may be in the form of separate inhalers or fixed-dose combination inhalers. Documented evidence of prescription for these medications, and/or medications must be provided. A verbal history from the participant is not considered sufficient.
- Individual component changes or switches between devices are allowed as long as the participant remains on the same class therapies in equivalent doses.
- SAMA taken at regular scheduled intervals (at a minimum frequency of 3 times daily) will be considered equivalent to LAMA.
- If a participant is being treated with oral COPD maintenance therapy (for example, azithromycin, roflumilast), these treatments must also be stable for at least 3 months prior to screening (Visit 1)
6. CAT score greater than or equal to 10 at Visit 1.
7. Current or ex-smokers with a cigarette smoking history of greater than or equal to 10 pack-years.
Pack-years are calculated as the average number of cigarettes per day multiplied by number of years divided by 20. For example, one pack-year equals 20 cigarettes smoked per day for one year or 10 cigarettes per day for 2 years
a. Former smokers will be defined as participants who are currently not smoking and with smoking cessation greater than or equal to 6 months prior to screening with an intention to quit permanently.
b.Electronic cigarette (e-cigarette; referring to devices that vaporise liquids such as nicotine, tetrahydrocannabinol) and heated tobacco product use do not contribute to the pack-year count for eligibility
8. Participants who are clinically stable and free from an exacerbation of COPD for 4 weeks prior to Visit 1 and remain exacerbation free at Visit 3 (randomisation).
9. Participants who are willing to remain on current COPD therapy throughout the trial (exception an AE requiring change in therapy).
10. Negative pregnancy test at Visit 1 and Visit 3 for WOCBP.
11. At least 70 percent compliance with participant s maintenance COPD therapy within 2 weeks immediately before Visit 3.
12. At least 70 percent compliance with PRO completion during the final 14 days of the screening period. This is assessed as evening e-diary completion of at least 10 days during the 14 days preceding Visit 3 (randomisation visit).
13. Participants who are able to read, write, and use electronic devices
Weight
14. BMI within the range 18 to 44.9 kilograms per square metre (inclusive).
Sex and Contraceptive/Barrier Requirements
15. WNOCBP are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are post-menopausal. The following age-specific requirements apply
- Females less than 50 years old would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and have FSH levels in the post-menopausal range.
- Females greater than or equal to 50 years old would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
Contraceptive use for participants of childbearing potential should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- All WOCBP participants who are sexually active with a non-sterilised male partner must agree to use one highly effective method of contraception (see list below).
- WOCBP participants must be stable on their approved contraceptive method for at least 3 months before Visit 3, throughout the entire duration of the study and for 2 weeks after the last dose of IMP. The non-sterilised male partner of the WOCBP participant must use a condom, starting from screening, throughout the entire duration of the study and for 2 weeks after the last dose of IMP.
- All non-sterilised male participants who are sexually active with a WOCBP must agree to use condoms starting from randomisation, during the study and 2 weeks after the last dose of IMP. The WOCBP partner must agree to use one highly effective method of contraception, must be stable on their approved contraceptive method for at least 3 months before Visit 3, throughout the entire duration of the study, and for 2 weeks after the last dose of IMP
Highly effective contraceptive methods for WOCBP participants include
- Non-hormonal methods
- Total 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)
- Bilateral tubal occlusion (caveat failure rate greater than 1 percent)
- Intrauterine device (copper)
The following are not acceptable methods of contraception for WOCBP participants
- Periodic abstinence (calendar, symptothermal, post-ovulation methods)
- Withdrawal (coitus interruptus)
- Spermicides only
- Lactational amenorrhoea
- Female condom
- Hormonal methods
- Levonorgestrel intrauterine system
- Medroxyprogesterone injections
- Combined oral or transdermal contraceptives (ethinyl oestradiol plus progestin)
- Intravaginal device (for example, ethinyl oestradiol and etonogestrel)
- Intrauterine hormone-releasing system
Informed Consent
1. Capable of giving signed informed consent as described in protocol, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, or analysis.
3. Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional Genomics Initiative Research that supports the Genomics. Not applicable to participants in China.
4. Provision of signed and dated written HRCT sub-study consent prior to sub-study procedures (if applicable).
5. Provision of signed and dated written participant experience interview sub-study consent prior to sub-study procedures
ExclusionCriteria
Details
Participants are excluded from the study if any of the following criteria apply
Medical Conditions
1 Clinically important pulmonary disease other than COPD (eg, asthma [current diagnosis per GINA or other accepted guidelines], active pulmonary infection, clinically significant bronchiectasis when bronchiectasis is the predominant diagnosis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha-1 antitrypsin deficiency or primary ciliary dyskinesia). A prior misdiagnosis of asthma or a history of asthma is not exclusionary.
2 Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant’s respiratory symptoms.
(a) Radiological findings of pulmonary nodule(s) suspicious for lung cancer, as per applicable guidance (eg, ACR Lung-RADS v2022,) without appropriate follow-up before Visit 3.
(b) Recent lung imaging result that requires immediate diagnostic investigation or follow-up. If initial repeat surveillance imaging has been undertaken, and the abnormality is considered as low risk for malignancy, the participant may be eligible for enrolment. Applicable also for participants taking part in the optional HRCT scan sub-study.
3 Any unstable disorder, including, but not limited to, CV, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that, in the opinion of the investigator, could:
(a) Affect the safety of the participant throughout the study.
(b) Influence the findings of the study or their interpretation.
(c) Impede the participant’s ability to complete the entire duration of the study and/or comply with the study visit schedule and procedures.
4 Participants with the following medical conditions
(a) Significant left heart failure (ie, New York Heart Association Functional Classification class III and IV or left ventricular ejection fraction less than 40 percentage on echocardiogram or cardiac MRI, if such results are available).
(b) Unstable angina, acute coronary syndrome/acute myocardial infarction or coronary intervention with percutaneous coronary intervention/coronary artery bypass graft within 6 months of randomisation, uncontrolled arrhythmia, or cardiomyopathy, clinically significant aortic stenosis, or signs of pulmonary oedema or volume overload(c) Pulmonary arterial hypertension, either idiopathic or due to connective tissue or thromboembolic disease.
Note: Participants with pulmonary arterial hypertension due to chronic lung disease are eligible.
(d) History of another underlying condition that predisposes the participant to infections (eg, history of splenectomy, known primary or secondary immune deficiency syndromes).
(e) History of ulcerative colitis, Crohn s disease, or microscopic colitis diagnosed by either a gastroenterologist or by histopathology.
(f) Presence of greater that 10percentage BSA depigmentation (eg, vitiligo or other causes of hypopigmentation) at baseline (Visit 3), at the discretion of the investigator.
5 The following abnormal laboratory findings at screening:
(a) ALT or AST greater than 2 × ULN
(b) TBL greater than 2 × ULN (unless due to Gilbert s disease)
(c) Hb less than 120 g/L (males); Hb less than 110 g/L (females)
(d) WBC less than LLN, neutrophil count less than 2.5 × 109/L, platelet count less than 150 × 109/L
(e) Estimated glomerular filtration rate less than 45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration formula.
Note: Abnormal laboratory values can be repeated once during screening (unless the sample was clotted, delayed in processing, otherwise mishandled, or a laboratory error is suspected, then additional repeat testing is allowed).
6 Any clinically significant abnormalities in the 12-lead ECG that, in the investigator s opinion, would put the participant at increased risk. Atrial fibrillation is not exclusionaryif the rate is well controlled, and the participant has been on stable anticoagulant therapy for at least 8 weeks.
7 Participants with evidence of active liver disease and/or evidence of chronic liver disease. Any of the following would exclude the participant from the study:
(a) Participants who test positive for hepatitis C antibody, unless HCV RNA levels are undetectable prior to randomisation. Please note that if the participant has undergone treatment for HCV, then the RNA level must be assessed more than 12 weeks following the end of treatment.
(b) Positive hepatitis B surface antigen or a positive medical history for hepatitis B. Participants with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol.
8 Participants with history of HIV infection or who test positive for HIV.
9 History of a clinically significant infection (viral, bacterial, or fungal; defined as requiring systemic antibiotics, antiviral, or antifungal medication for greater than 7 days) within 4 weeks prior to Day 1 (Visit 3) (including unexplained diarrhoea) or clinical suspicion of infection at the time of dosing. Participants can rescreen after the infection has resolved.
10 History of lung volume reduction surgery.
11 History of bronchial thermoplasty or endobronchial valves within 6 months prior to Visit 1.
12 Use, or need for chronic use, of any NIPPV. Stable use of non-invasive ventilation for the treatment of obstructive sleep apnoea is permitted.
13 Current or history of malignancy within 5 years before the screening visit with the following exceptions:
(a) Low risk prostate cancer under active surveillance
(b) Completely treated in situ carcinoma of the cervix
(c) Ductal carcinoma in situ of the breast or localised medullary cancer of the thyroid successfully treated with surgery with no evidence of recurrence for at least one year
(d) Participants with basal cell or superficial squamous skin cancer
14 History of, or a reason to believe a participant has a history of, drug or alcohol abuse within the past one year prior to screening.
15 Participants who, as judged by the investigator, have evidence of active TB, either treated or untreated, or latent TB without completion of an appropriate course of treatment or appropriate ongoing prophylactic treatment. Evaluation will be according to the local SoC as determined by local guidelines and may consist of history and physical examinations, chest X-ray, or TB test (eg, purified protein derivative or QuantiFERON® test).
16 Male or female participants who wish to conceive a child or donate sperm or ova during the study and for the 2 weeks after the last dose of IMP.
Prior/Concomitant Therapy
1 Participants currently receiving background therapy for COPD that is not approved by regulatory authorities in the country of study (with the exception of nicotine vaping products or patches).
2 Major surgery within 8 weeks prior to screening or planned inpatient surgery or hospitalisation during the study period.
3 Treatment with a broad-spectrum antibiotic (excluding long-term azithromycin) within 28 days (4 weeks) prior to randomisation (Visit 3).
4 Donation of blood or blood products within 3 months prior to screening.
5 History of allogeneic bone marrow transplant.
6 Participant who is going to start a COPD rehabilitation programme at any time during the study period. Participants can be recruited immediately following the completion of their COPD rehabilitation programme. Ongoing maintenance programs will be permitted.
7 Receiving any of the prohibited concomitant medications as specified in the CSP:
(a) Acute systemic (oral or injectable) corticosteroids within 28 days (4 weeks) of Visit 1.
(b) Any other immunosuppressive therapy (including methotrexate, cyclosporine, tacrolimus, azathioprine, or maintenance systemic steroid treatment) within 3 months of randomisation. Courses of systemic corticosteroids not exceeding 8 weeks for the treatment of acute or self-limiting conditions that ended before 4 weeks of Visit 1 are permitted.
(c) Immunoglobulin, interferon gamma, or blood products within 28 days (4 weeks) of Visit 1.
(d) Certain CYP-interacting medications 14 days (2 weeks) prior to Visit 3.
(e) Metformin 14 days (2 weeks) prior to randomisation (Visit 3).
(f) IMPs within 4 months or 5 half-lives of randomisation, whichever is longer.
(g) Marketed biologics for respiratory diseases within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
Note: Participants on stable therapy for at least 8 weeks prior to randomisation who intend to stay on treatment throughout the study with marketed biologics for
non-respiratory diseases that are not likely to interfere with the assessment of safety and/or efficacy of AZD6793 (eg, for the treatment of osteoporosis, migraine, pain, diabetes, obesity, ocular, CV, or metabolic diseases) can participate in the study.
(h) Long-term-oxygen therapy greater than 4.0 L/minute. While breathing supplemental oxygen, participants must demonstrate an oxyhaemoglobin saturation greater than or equal to 89percentage. To be admitted
to the study, participants on long-term oxygen therapy must be ambulatory and able to attend clinic visits. Note: As-needed oxygen use is allowed.
17 Any concomitant medications known to be associated with Torsades de Pointes.
Prior/Concurrent Clinical Study Experience
18 Participants with a known hypersensitivity to AZD6793 or any of the excipients of the product.
19 Concurrent enrolment in another clinical study involving an investigational treatment.
Other Exclusions
20 Participant is an investigator, sub-investigator, study coordinator, or employee of the participating site or AstraZeneca or is a first-degree relative of the aforementioned.
21 Inability to perform technically acceptable spirometry.
22 Randomisation of participant is not permitted due to closure of stratum.
23 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
24 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.
25 Previous enrolment or randomisation in the present study or previous treatment with AZD6793.
26 For females only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding. All WOCBP participants must have a negative pregnancy test result at Visit 1 (serum) and Visit 3 (urine).
1.1 Lifestyle Considerations
1.1.1 Meals and Dietary Restrictions
Participants should avoid eating a large meal for at least 2 hours prior to spirometry. Grapefruit juice should be avoided for 14 days (2 weeks) prior to Visit 3, during the study and for 2 days following discontinuation of AZD6793.
1.1.2 Caffeine, Alcohol, and Tobacco
- CYP1A2 is the main enzyme catalysing the metabolism of caffeine (more than 95percentage). Downregulation of CYP1A2 mRNA levels in hepatocytes in the presence of AZD6793 has been observed in vitro, but whether this finding translates to a clinically relevant DDI is currently unknown. Excessive use of caffeine during the study should be discouraged if it causes caffeine related symptoms such as tremors, palpitations, restlessness, and insomnia.
- Chronic excessive alcohol use or illicit drug use (per local laws) is not allowed within 12 months before Visit 1 and throughout the study.
- Current tobacco smokers should not smoke for 2 hours before any lung function assessment is performed.
- Current tobacco smokers should be encouraged to discontinue smoking.
1.1.3 Activity
- Participants will abstain from strenuous exercise for 48 hours before each blood collection for clinical laboratory tests. Participants may participate in light or moderate exercise (eg, walking, gardening, housework, bowling, light resistance training) in the 48 hours before each blood collection.
- Participants should avoid engaging in strenuous exertion for at least 30 minutes prior to all lung function assessments at the site.
1.1.4 Other Restrictions
- Participants must abstain from donating blood and plasma within 3 months prior to screening to one week (greater than 5 half-lives) after last dose of IMP.
- Participants must abstain from visits to skin tanning salons, using sunbeds, or having skin laser treatments from first dose of IMP until end of the study (Visit 9).
- SPF greater than or equal to 50 use required outdoors on sun-exposed skin between 1000 and 1600 (could be extended as per local guidelines), from first dose of IMP until end of the study (Visit 9)
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the effect of AZD6793 as compared to placebo on the rate of moderate or severe COPD exacerbations
To evaluate the effect of AZD6793 as compared to placebo on the rate of moderate or severe COPD exacerbations
Secondary Outcome
Outcome
TimePoints
To evaluate the effect of AZD6793 as compared to placebo on COPD exacerbations
Time to first moderate or severe COPD exacerbation.
Annualised rate of COPD exacerbations associated
with emergency room visits, urgent care visits, or hospitalisations.
Annualised rate of severe COPD exacerbations.
A severe COPD exacerbation is defined as an exacerbation resulting in hospitalisation (defined as an inpatient admission greater than or equal to 24 hours in the hospital, in an observation area, the emergency department, or other equivalent healthcare facility depending on the country and healthcare system) or death due to COPD.
To evaluate the effect of AZD6793 as compared to placebo on COPDCompEx events
Annualised rate of COPDCompEx events
Time to first COPDCompEx event
To evaluate the effect of AZD6793 compared to placebo on measures of lung function
Change from baseline in pre-BD FEV1 at Week 12 and Week 24
Change from baseline in post-BD FEV1 at Week 12 and Week 24
To evaluate the effect of AZD6793 compared to placebo on symptoms and HRQoL
Change from baseline over 24 weeks in each of the following
- BCSS total score
- CAT total score
- SGRQ total and domain scores
To assess the PK of AZD6793 in participants with moderate to very severe COPD
AZD6793 plasma concentrations at specific timepoints.
Target Sample Size
Total Sample Size="1160" Sample Size from India="60" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Current COPD therapies include combinations of inhaled long-acting beta two agonists, long-acting muscarinic antagonist, corticosteroids, and add-on oral anti-inflammatory agents such as roflumilast. However, current COPD therapies do not eliminate the symptoms, disability, or exacerbations that are associated with COPD, or significantly alter the course of COPD (Celli and Wedzicha 2019). Thus, a high unmet need remains and novel, more effective therapies are greatly needed. AZD6793 is an orally available, low molecular weight, and potent inhibitor of interleukin-one receptor–associated kinase four (IRAK4). IRAK4 is a key regulator of immune signalling and is expressed by multiple cells including innate and adaptive immune cells. It mediates signal transduction from Toll-like receptors (TLRs) and receptors of the interleukin-one (IL-one) family, including IL-oneR, IL-thirty sixR, and the IL-thirty three receptor suppression of tumorigenicity-two (ST2). AZD6793 has broad anti-inflammatory activity by inhibiting the pathways downstream of ST2 (the receptor for IL-thirty three), IL-one beta, IL-eighteen, and IL-thirty six receptors and various toll-like receptors. Based on data from pre-clinical studies, AZD6793 is expected to reduce both neutrophilic and eosinophilic inflammation and additionally reduce mucus production in the airways of patients with COPD. As exaggerated inflammation and mucus production in COPD airways contribute to the development of acute COPD exacerbations, it is hypothesised that AZD6793 may reduce acute exacerbation rates in patients with COPD also in addition to improving lung function and alleviating the symptom burden associated with COPD. AZD6793 also has the potential to reduce systemic inflammation and thereby reduce the development and progression of comorbidities that are associated with COPD.