Effects of anti-IL33 (tozorakimab) upon airway inflammation, remodelling and response to exacerbation triggers in chronic obstructive pulmonary disease (COPD) (The MAB Trial)
| ISRCTN | ISRCTN35638452 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN35638452 |
| Clinical Trials Information System (CTIS) | 2025-522359-24-00 |
| Integrated Research Application System (IRAS) | 1011840 |
| Central Portfolio Management System (CPMS) | 67199 |
| Protocol serial number | 1066 |
| Sponsor | University of Leicester |
| Funder | AstraZeneca |
- Submission date
- 07/08/2025
- Registration date
- 10/12/2025
- Last edited
- 26/08/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
COPD is characterised by chronic inflammation in the lungs which can leave you more likely to experience infections. The condition can be associated with a higher rate of morbidity and a reduced quality of life. For many years, the mainstay of COPD treatment has been inhaler medication that opens the airways. Despite this many people still suffer with exacerbations (worsening) of their COPD due to inflammation in the lungs. This can be triggered by many things, including infections. The mucous membranes in the lungs release proteins when irritated, including certain substances which lead to increased inflammation in the lungs.
The purpose of this study is to investigate the effects of a new type of medication in terms of what improvements it can achieve and how it improves inflammation and likelihood of getting exacerbations. We hope that treatment with Tozorakimab will reduce inflammation and airway damage in those with COPD. We are working with other research teams based in Europe and the United Kingdom.
Who can participate?
Overall, 80 patients with COPD will take part in the study at about 10 sites.
What does the study involve?
Of these 80 patients, half will be given Tozorakimab and half will be given a dummy drug, called a ‘placebo’. We will compare the results of those two groups.
In order to understand if the treatment works, we would like to collect information from participants including health questionnaires, exercise tests, and breathing tests, and blood, urine, nasal, and breath samples as well as collecting information from your clinical records. This study also involves two bronchoscopy examinations of the lungs where we will take samples. This will enable us to compare information between those who are receiving Tozorakimab and those who receive the placebo (dummy drug). Participation in the study takes place over 36 weeks and 15 visits.
What are the possible benefits and risks of participating?
Not provided
Where is the study run from?
University of Leicester (UK).
When is the study starting and how long is it expected to run for?
June 2026 to December 2027.
Who is funding the study?
AstraZeneca (UK).
Who is the main contact?
Dr Christopher Brightling, theMABtrial@leicester.ac.uk
Contact information
Scientific, Principal investigator
Glenfield Hospital
Leicester
LE5 4PW
United Kingdom
| theMABtrial@leicester.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Blinded (masking used) |
| Control | Placebo |
| Assignment | Parallel |
| Purpose | Treatment |
| Scientific title | Effects of anti-IL33 (tozorakimab) upon airway inflammation, remodelling and response to exacerbation triggers in chronic obstructive pulmonary disease (COPD) (The MAB Trial) |
| Study acronym | MAB |
| Study objectives | Primary objective: To evaluate the effect of Tozorakimab on: 1. Airway epithelial remodelling histology score 2. Granulocytic inflammation in the bronchial submucosa Secondary objective: To evaluate the effect of Tozorakimab on: 1. Thoracic CT 2. Patient-reported outcomes – CAAT, mMRC, SGRQ-C, symptom visual analogue scores (VAS) 3. Spirometry – FEV1, FVC, oscillometry 4. Biopsy – lymphocytes (CD3, CD4, CD8), epithelial integrity, epithelial remodelling markers, goblet cells, RBM thickening and airway smooth muscle area 5. Safety and tolerability |
| Ethics approval(s) |
Approved 08/10/2025, Seasonal REC (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8241; seasonal.rec@hrs.nhs.uk), ref: 25/LO/0628 |
| Health condition(s) or problem(s) studied | Chronic Obstructive Pulmonary Disease (COPD) |
| Intervention | This study is a randomised, double-blind, placebo-controlled trial. It includes a maximum enrolment period of 4 weeks, 24 weeks of treatment (6 doses of 300mg Tozorakimab or placebo SC every 4 weeks to week 20), and a 12-week follow-up period. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Tozorakimab |
| Primary outcome measure(s) |
1. Improvement in the semi-quantitative epithelial remodelling histology score from baseline to week 24 |
| Key secondary outcome measure(s) |
1. Thoracic CT |
| Completion date | 31/12/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 40 Years |
| Upper age limit | 85 Years |
| Sex | All |
| Target sample size at registration | 96 |
| Key inclusion criteria | 1. Willing and able to consent to participate in the trial 2. Age ≥ 40 <85 years old 3. Male or female 4. Able to understand written and spoken English (UK participants) or country’s official language (non-UK participants) 5. Clinically diagnosed chronic obstructive airway disease at least 1-year prior screening 6. FEV1/FVC<0.7 and FEV1 ≥ 30% predicted value (and ≥ 1.0L) at Visit 1 7. Current or ex-smokers with ≥ 10 pack years past smoking history (25-40% of participants will be current smokers) a. Former smokers will be defined as participants who are currently not smoking and with smoking cessation ≥ 6 months before screening with an intention to quit permanently b. Current smokers will be defined as participants who are currently smoking tobacco (at least one cigarette per day on average during the past 7 days) and are not presently participating in smoking cessation c. Electronic cigarettes (e-cigarettes referring to devices that vaporise liquids [e.g., nicotine, THC]) and heated tobacco product use do not contribute to the pack-year count for eligibility. E-cigarette smoking/heated tobacco smoking status being irrelevant to categorisation/randomisation 8. On stable treatment for at least 3 months prior to screening with COPD inhaled maintenance dual or triple therapy. During this period: a. Individual component changes or switches between devices are allowed if the participant remains on the same class therapies in equivalent doses b. Short-term changes in background treatment regimen during COPD exacerbation are acceptable. c. Short-acting muscarinic antagonists taken at regular scheduled intervals (at a minimum frequency of 3 times daily) will be considered equivalent to LAMA d. If the participant is being treated with oral COPD maintenance therapy (macrolides, roflumilast), these treatments must also be stable for at least 3 months before enrolment 9. History of ≥1 moderate to severe exacerbation event treated with systemic corticosteroid and/or antibiotic in the 12 months prior to screening. 10. CAAT ≥10 and cough and sputum domain ≥2 at Visit 1 11. Women of childbearing potential (WOCBP) and males must be willing to use a highly effective method of contraception |
| Key exclusion criteria | 1. Any unstable disorder, including, but not limited to, cardiovascular, 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 2. Significant concomitant respiratory diseases, such as cystic fibrosis, and pulmonary fibrosis. 3. Any significant abnormal laboratory results at screening, which, in the opinion of the investigator, may put the subject at risk if taking take part in the study 4. Current diagnosis of asthma 5. Long-term oxygen therapy or NIPPV for type 2 respiratory failure. Participants using continuous positive airway pressure for sleep apnoea syndrome are permitted in the study 6. Recent acute exacerbation event requiring oral corticosteroids or antibiotics (any dose for more than 3 days) or respiratory tract infection within 4 weeks prior to screening 7. Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms 8. History of any known primary immunodeficiency disorder excluding asymptomatic selective immunoglobulin A or IgG subclass deficiency 9. Subject taking antiretroviral medications, as determined by medical history 10. Hepatitis: Medical history of or treatment for hepatitis B or hepatitis C, except for cured hepatitis C. a. Positive test for HBsAg b. Positive test for anti-HBc: Participants who test positive for anti-HBc antibody but negative for HBsAg may be enrolled if their HBV DNA test result is negative c. Positive test for anti-hepatitis C antibody: 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 |
| Date of first enrolment | 23/06/2026 |
| Date of final enrolment | 31/03/2027 |
Locations
Countries of recruitment
- United Kingdom
- Denmark
- Italy
- Netherlands
- Spain
Study participating centres
Leicester
LE3 9QF
England
St Marys Hospital
South Wharf Road
London
W2 1BL
England
Westminster Bridge Road
London
SE1 7EH
England
Southmoor Road
Wythenshawe
Manchester
M23 9QZ
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
26/08/2026: The information for which publication was previously deferred has been added to the following fields:
1. The public title
2. The scientific title
3. Study hypothesis
4. Condition
5. Interventions
6. Drug name(s)
7. Primary outcome measure
8. Secondary outcome measures
9. Participant inclusion criteria
10. Participant exclusion criteria
11. Plain English summary
In addition the following changes were made to the study record:
1. The Date of first enrolment was changed from 31/08/2025 to 23/06/2026.
2. Italy was added to the countries of recruitment.
3. The study participating centres were updated.
04/03/2026: The study contacts were updated.
21/01/2026: Internal review.
08/08/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)
