Effects of blocking TSLP on airway inflammation and the epithelial immune response to exacerbation triggers in patients with COPD (UPSTREAM-COPD)
Chronic obstructive pulmonary disease
Participants will be randomised in a 1:1 ratio to IMP versus placebo. The trial team and participants will be blinded to treatment assignment. Randomisation will be stratified based on blood eosinophil counts at baseline (< or ≥ 0.2 x109 /L) and smoking status. The blocked randomisation method will be used in this study. Pre-defined clusters of randomised strata will be distributed from the Danish site along with study medication and randomisation in sealed envelopes before the start of the study. Once all eligibility criteria are met, the study nurse will enter the data on smoking status and baseline eosinophil count. The assigned strata with randomised IDs will be subsequently generated. The drug arm will receive 210 mg tezepelumab, given by subcutaneous injection every 4 weeks for a total of 5 doses. The placebo arm will receive a blinded dose of 0.9% saline subcutaneously at the same frequency and for the same duration. These will be administered by trial staff at each visit. Both arms receive the same follow-up. The central pharmacy from the Denmark site will be responsible for receiving and labelling IMP for all sites according to a randomisation list prepared by a computerized system. They will inform the local pharmacy/team which numbered vial to administer to each patient as randomised. They will centrally monitor the stock of IMP and placebo in each site, ensuring appropriate stocks are always available. Clinical teams at all sites will be blinded to the intervention.
1. Willing and able to consent to participate in the trial 2. Clinically diagnosed chronic obstructive airway disease with post-bronchodilator FEV1 ≥ 30% to 80% predicted value (and ≥ 1.0 L) 3. Age ≥40 years old 4. Current or ex-smokers with ≥ 10 pack-years of past smoking history 5. Stable airway disease status on maintenance inhaled therapy (LAMA + LABA ± ICS) for at least 3 months prior to screening 6. History of ≥1 moderate-to-severe exacerbation event treated with prednisolone and/or antibiotic in the past 12 months 7. Good compliance with daily inhaler regime (≥70% adherence rate) at screening
1. History of unstable or severe cardiac, hepatic, thyrotoxicosis, concomitant respiratory or renal disease, or other medically significant illness, which the investigator believes would be a contraindication to study participation. 2. Significant concomitant respiratory disease such as cystic fibrosis, pulmonary fibrosis, aspergillosis, active or untreated primary tuberculosis. 3. Any significant abnormal laboratory results at screening, which in the opinion of the investigator, may put the subject at risk to take part in the study 4. Current diagnosis of asthma 5. Previous lung volume reduction surgery for the indication of COPD 6. Any use of home oxygen therapy 7. Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening 8. Recent acute exacerbation event requiring oral corticosteroids or antibiotics (any dose for more than 3 days) or respiratory tract infection 4 weeks prior to screening 9. History of active Malignancy in any organ system (diagnosis within last 12 months or ongoing active cancer treatment such as chemotherapy, radiotherapy, or immunotherapy. 10. History of treatment with biologics within four months or five half-lives (whichever is longer) prior to screening. 11. History of anaphylaxis to any biologic therapy or sensitivity of any component of IMP formulation 12. Have been involved in another medicinal trial (CTIMP) within the past 28 days 13. Women who are pregnant, lactating or intend to become pregnant during the study period 14. Planned surgical procedures requiring general anaesthesia or in-patient status for > 1 day during the conduct of the study. 15. Receipt of any live or attenuated vaccines within 15 days prior to screening 16. Patients whose treatment is considered palliative (life expectancy < 6 months). 17. History of chronic alcohol or drug abuse within 12 months prior to screening 18. Receipt of immunoglobulin or blood products within 30 days prior