UPSTREAM-COPD

Summary:  

COPD (chronic obstructive pulmonary disease) is a highly common chronic lung disease which carries a significant burden for both patients and healthcare systems. Treatment has been limited for a number of years. Recent studies have shown a promising new target in treating asthma – Thymic stromal lymphopoeitin (TSLP) is a protein released when the airways are irritated. This causes an increase in airway inflammation and therefore the symptoms COPD. Blocking or reducing this with a medication called tezepelumab has been shown to reduce airway inflammation in asthma. Other studies have also shown reduced symptoms and exacerbations in a diverse group of asthma patients, including in those who do not demonstrate a high level of allergic type inflammation. 

We hope to study the effect of this medication in the airway of people who suffer from COPD. We intend to do this by recruiting patients to three sites – Copenhagen, Leicester and London. These will be people with moderate to severe COPD, on standard inhaled treatment with at least one exacerbation in the preceding twelve months. Those who are willing to be involved and fulfil screening criteria will have various baseline blood and breathing tests along with questionnaires completed. Everyone will undergo a bronchoscopy – a test where a fine, flexible camera is inserted into the lungs and samples and biopsies can be taken. 50% of people will be randomised to receive the medication and 50% will receive a placebo. Each person and the team looking after them directly will not know which one they are receiving. They will receive this 4 weekly for 5 doses total, then undergo a repeat bronchoscopy and other tests. The total study time will be approximately 22 weeks. If this trial is successful it may contribute to evidence allowing us to use tezepelumab to treat COPD in future.

Non-Commercial Study

Type of Study:  

PIC study

Is this Study Applicable to the RSI Scheme? 

For the purpose of the RSI scheme this study will count as a PIC Study

Practice Activity: 

• Database search

• GP to check list for exclusions

• Mail out

Optional Pharmacy within GP Practice Activity: 

Not applicable for this study

Practice Eligibility Criteria: 

Practices within NHS Leicester, Leicestershire and Rutland ICB have been pre-selected by the study team

Practice Target:  

No particular practice target

Participant Eligibility Criteria:

Inclusion Criteria: 

• Willing and able to consent to participate in the trial

• Clinically diagnosed chronic obstructive airway disease with post bronchodilator FEV1 ≥ 30% to 80% predicted value (and ≥ 1.0L)

• Age ≥ 40 years old

• Current or ex-smokers with ≥ 10 pack years past smoking history

• Stable airway disease status on maintenance inhaled therapy (LAMA+LABA±ICS) for at least 3 months prior to screening

• History of ≥1 moderate to severe exacerbation event treated with prednisolone and/or antibiotic in the past 12 months

• Good compliance with daily inhaler regime (≥ 70% adherence rate) at

• Screening

Exclusion Criteria:

• 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.

• Significant concomitant respiratory disease such as cystic fibrosis, pulmonary fibrosis, aspergillosis, active or untreated primary tuberculosis.

• 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,

• Current diagnosis of Asthma

• Previous Lung volume reduction surgery for the indication of COPD

• Any use of home oxygen therapy

• Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening

• 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

• History of active Malignancy in any organ system (diagnosis within last 12 months or ongoing active cancer treatment such as chemotherapy, radiotherapy, or immunotherapy.

• History of treatment with biologics within four months or five half-lives (whichever is longer) prior to screening.

• History of anaphylaxis to any biologic therapy or sensitivity of any component of IMP formulation

• Have been involved in another medicinal trial (CTIMP) within the past 28 days

• Women who are pregnant, lactating or intend to become pregnant during the study period

• Planned surgical procedures requiring general anaesthesia or in-patient status for > 1 day during the conduct of the study.

• Receipt of any live or attenuated vaccines within 15 days prior to screening

• Patients whose treatment is considered palliative (life expectancy < 6 months).

• History of chronic alcohol or drug abuse within 12 months prior to screening

• Receipt of immunoglobulin or blood products within 30 days prior to screening

• Use of immunosuppressive medication (e.g., methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid) within 3 months prior to screening.

• History of any known primary immunodeficiency disorder excluding asymptomatic selective immunoglobulin A or IgG subclass deficiency.

• Subject taking antiretroviral medications, as determined by medical history

• History of human immunodeficiency virus (HIV) or hepatitis B or C.

Is this Study Applicable for the Associate PI Scheme?  

Not applicable for this study

Resources Provided by the Study Team: 

Study information packs

Costs to be Provided by the Study Team (Research and Service Support Costs):

• Per-practice fee for PIC set up: £350

• Per patient randomised: £80 

All costs will be provided by the study team. Please contact the study team via the email address below and they will confirm how these can be claimed.  

Excess Treatment Costs: 

Not applicable for this study

Participant in Research Experience Survey (PRES):

Participant in Research Experience Survey (PRES), is an annually standardised survey used to collect adults and children's views and experiences of participating in NIHR supported research. 

The study is not applicable for PRES.  

Contact Details:

Sarah Edwards 

sarah.edwards141@nhs.net