Effects of Blocking TSLP on Airway Inflammation and the Epithelial Immune-response to Exacerbation Triggers in Patients With COPD

Inclusion Criteria:

• Written informed consent

• A diagnosis of COPD (according to GOLD (GOLD 2021 Report))

• ≥ 10 packyears smoked (current or ex-smokers)

• Age 40 years or older

• Postbronchodilator FEV1 ≥ 30% predicted (and ≥ 1.0L) and < 80% predicted

• Maintenance treatment with LAMA+LABA±ICS (stable dose) for at least 3 months priorto V1

• ≥1 prednisolon and/or antibiotic treated exacerbation in the past 12 months

• Subjects must demonstrate acceptable inhaler and spirometry techniques duringscreening (as evaluated and in the opinion of study site staff)

• Subjects must demonstrate ≥ 70% compliance with daily inhalers during thescreening/run-in

• Females of childbearing potential who are sexually active with a nonsterilized malepartner must use a highly effective method of contraception from the time informedconsent is obtained and must agree to continue using such precautions through Week 20 of the study; cessation of contraception after this point should be discussedwith a responsible physician. Periodic abstinence, the rhythm method, and thewithdrawal method are not acceptable methods of contraception. Females ofchildbearing potential are defined as those who are not surgically sterile (ie,bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) orpostmenopausal (defined as 12 months with no menses without an alternative medicalcause).

Exclusion Criteria:

• Previous medical history or evidence of an uncontrolled intercurrent illness that inthe opinion of the investigator may compromise the safety of the subject in thestudy or interfere with evaluation of the investigational product or reduce thesubject's ability to participate in the study. Subjects with well-controlledcomorbid disease (eg, hypertension, hyperlipidemia, gastroesophageal reflux disease)on a stable treatment regimen for 15 days prior to Visit 1 are eligible.

• Any concomitant respiratory disease that in the opinion of the investigator willinterfere with the evaluation of the investigational product or interpretation ofsubject safety or study results (e.g., cystic fibrosis, pulmonary fibrosis,aspergillosis, active tuberculosis).

• Current asthma

• Lung volume reduction surgery for COPD

• Exacerbation requiring oral corticosteroids or antibiotics (any dose for more than 3days) 4 weeks prior to Visit 1 or during the run-in period

• Any use of home oxygen therapy

• Any clinically relevant abnormal findings in hematology or clinical chemistry (laboratory results from Visit 1), physical examination, vital signs during thescreening, which in the opinion of the investigator, may put the subject at riskbecause of his/her participation in the study, or may influence the results of thestudy, or the subject's ability to participate in the study

• History of cancer: Subjects who have had basal cell carcinoma or in situ carcinomaof the cervix are eligible to participate in the study provided that curativetherapy was completed at least 12 months prior to Visit 1. Subjects who have hadother malignancies are eligible provided that curative therapy was completed atleast 5 years prior to Visit 1.

• Acute upper or lower respiratory infections requiring antibiotics or antiviralmedications within 4 weeks prior to Visit 1 or during the screening period

• A positive human immunodeficiency virus (HIV) test at screening or subject takingantiretroviral medications, as determined by medical history

• Positive hepatitis B surface antigen, or hepatitis C virus antibody serology atscreening, or a positive medical history for hepatitis B or C. Subjects with ahistory of hepatitis B vaccination without history of hepatitis B are allowed toenroll.

• History of sensitivity to any component of the investigational product formulationor a history of drug or other allergy that, in the opinion of the investigator ormedical monitor contraindicates their participation.

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

• Active tuberculosis or history of untreated latent tuberculosis

• History of anaphylaxis to any biologic therapy.

• Use of immunosuppressive medication (eg, methotrexate, troleandomycin, oral gold,cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, or anyexperimental anti-inflammatory therapy) within 3 months prior to Visit 1.

• Receipt of any of the following within 30 days prior to Visit 1: immunoglobulin orblood products, or receipt of any investigational nonbiologic agent within 30 daysor 5 half-lives prior Visit 1, whichever is longer.

• Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives prior to Visit 1, whichever is longer.

• Pregnant, breastfeeding or lactating females

• History of chronic alcohol or drug abuse within 12 months prior to Visit 1.

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

• Unwillingness or inability to follow the procedures outlined in the protocol.

• Concurrent enrollment in another clinical study involving an investigationaltreatment.

• Receipt of any live or attenuated vaccines within 15 days prior to Visit 1.