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

NCT05507242 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UPSTREAM-COPD
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 2

Brief Summary

A phase 2, multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the effect of tezepelumab on airway inflammation in patients with COPD.

Conditions

COPD; COPD Exacerbation; COPD Bronchitis; Airway Disease; Immune System Disorder

Keywords

COPD

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of tezepelumab on eosinophilic bronchial mucosal tissue inflammation

  The change, expressed as ratio, in eosinophil cell counts per mm2 from baseline to week-20

  20 weeks

Secondary Outcomes (5)

• To evaluate the effect of tezepelumab on neutrophilic bronchial mucosal tissue inflammation

  20 weeks

• To evaluate the effect of tezepelumab on mast cell bronchial mucosal tissue inflammation

  20 weeks

• To evaluate the effect of tezepelumab on CD4+ cell bronchial mucosal tissue inflammation

  20 weeks

• To evaluate the effect of tezepelumab on CD8+ cell bronchial mucosal tissue inflammation

  20 weeks

• To evaluate the effect of tezepelumab on macrophage cell bronchial mucosal tissue inflammation

  20 weeks

Study Arms (2)

Tezepelumab

EXPERIMENTAL

Tezepelumab subcutaneous injection

Biological: Tezepelumab

Placebo

PLACEBO COMPARATOR

Placebo subcutaneous injection

Other: Placebo

Interventions

Tezepelumab BIOLOGICAL

Tezepelumab 210 mg for 20 weeks (5 doses in total, 4-week intervals), administered subcutaneously

Tezepelumab

Placebo OTHER

Placebo subcutaneous injection for 20 weeks (5 doses in total, 4-week intervals)

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 prior to V1
• ≥1 prednisolon and/or antibiotic treated exacerbation in the past 12 months
• Subjects must demonstrate acceptable inhaler and spirometry techniques during screening (as evaluated and in the opinion of study site staff)
• Subjects must demonstrate ≥ 70% compliance with daily inhalers during the screening/run-in
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time informed consent is obtained and must agree to continue using such precautions through Week 20 of the study; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).

You may not qualify if:

• Previous medical history or evidence of an uncontrolled intercurrent illness that in the opinion of the investigator may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study. Subjects with well-controlled comorbid 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 will interfere with the evaluation of the investigational product or interpretation of subject 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 3 days) 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 the screening, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to participate in the study
• History of cancer: Subjects who have had basal cell carcinoma or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to Visit 1. Subjects who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to Visit 1.
• Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 4 weeks prior to Visit 1 or during the screening period
• A positive human immunodeficiency virus (HIV) test at screening or subject taking antiretroviral medications, as determined by medical history
• Positive hepatitis B surface antigen, or hepatitis C virus antibody serology at screening, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enroll.
• History of sensitivity to any component of the investigational product formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor contraindicates their participation.
• History of any known primary immunodeficiency disorder excluding asymptomatic selective immunoglobulin A or IgG subclass deficiency.
• Active tuberculosis or history of untreated latent tuberculosis
• History of anaphylaxis to any biologic therapy.

Sponsors & Collaborators

• Asger Sverrild: lead
• AstraZeneca: collaborator
• University Hospitals, Leicester: collaborator

Study Sites (2)

Research site

Copenhagen, 2400, Denmark

RECRUITING

Research site

Leicester, LE3 9QP, United Kingdom

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Immune System Diseases

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Asger Sverrild, MD, PhD

  Bispebjerg Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristoffer Norheim, PhD

CONTACT

+4542831337; kristoffer.norheim@regionh.dk

Asger Sverrild, MD, PhD

CONTACT

asger.sverrild@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Clinical Associate Professor

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: August 18, 2022
• Study Start: October 25, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08

Locations

DK (1); GB (1)