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Effects of blocking a messaging protein called TSLP (thymic stromal lymphopoietin) on inflammation in the airways

Phase 2
Conditions
Chronic obstructive pulmonary disease
Respiratory
Registration Number
ISRCTN14181775
Lead Sponsor
niversity of Leicester
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing
Sex
All
Target Recruitment
80
Inclusion Criteria

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 = 1.0L)
3. Age = 40 years old
4. Current or ex-smokers with = 10 pack years 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

Exclusion Criteria

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 to screening
19. Use of immunosuppressive medication (e.g., methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid) within 3 months prior to screening. 
20. History of any known primary immunodeficiency disorder excluding asymptomatic selective immunoglobulin A or IgG subclass deficiency.  
21. Subject taking antiretroviral medications, as determined by medical history  
22. History of human immunodeficiency virus (HIV) or hepatitis B or C.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
The change in eosinophil cell counts in bronchial mucosa is measured using the samples obtained in bronchial biopsy using immunohistochemistry (IHC) at baseline and end of study (week 20)
Secondary Outcome Measures
NameTimeMethod
Evaluating the effect of tezepelumab on bronchial mucosal tissue inflammation by measuring the change in inflammatory cell counts using immunohistochemistry from baseline to week 20
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