Opening the "Black Box" on Tezepelumab's Effect on Chronic Rhinosinusitis With Severe Asthma

NCT06740045 | Not Yet Recruiting Phase 3

• 1 other identifier: H24-02151
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study explores how chronic rhinosinusitis (CRS) and asthma share a common inflammatory process, particularly affecting patients with both conditions. Interaction between immune cells (Interleukins) and Th2 cytokines, such as TSLP, exacerbates asthma control in CRS patients, especially those with nasal polyps (CRSwNP). TSLP plays a pivotal role in initiating and maintaining airway inflammation in both diseases. Tezepelumab, a biologic therapy targeting TSLP, shows promise in reducing inflammation markers in severe asthma but its impact on CRSwNP and quality of life remains unclear. The study proposes investigating Tezepelumab's efficacy in treating CRSwNP and severe asthma to inform future biologic therapies.

Conditions

Asthma; Chronic Rhinosinusitis With Nasal Polyps

Outcome Measures

Primary Outcomes (6)

• Eosinophil Count

  Measurement of eosinophil count in tissue samples. Cells per high power field (HPF) or cells per millimeter squared (cells/mm²).

  From baseline to 24 weeks

• Neutrophil count

  Measurement of neutrophil count in tissue samples. Cells per high power field (HPF) or cells per millimeter squared (cells/mm²).

  From baseline to 24 weeks.

• Basement Membrane Thickness

  Measurement of the thickness of the basement membrane in tissue samples. Micrometers (µm)

  From baseline to 24 weeks

• Fibrosis

  Assessment of the extent of fibrosis in tissue samples, which may involve scoring systems or quantitative measurements

  From baseline to 24 weeks

• Squamous Metaplasia

  Immunohistochemical staining will be used to identify the presence of squamous metaplasia, with scoring based on percentage of positive cells.

  From baseline to 24 weeks

• Lymphocytic Proliferation

  Lymphocytic proliferation will be assessed using immunohistochemistry (IHC) to measure the Ki-67 proliferation index in tissue samples, specifically identifying the percentage of Ki-67-positive lymphocytes

  From baseline to 24 weeks

Secondary Outcomes (12)

• Immunoglobulin leves

  24 weeks

• Th2 Cytokines

  24 weeks

• Th1/Th17 Cytokines

  24 weeks

• Myeloperoxidase (MPO)

  24 weeks

• Interferon-γ (IFN-γ)

  24 weeks

Study Arms (1)

Tezepelumab

EXPERIMENTAL

Tezepelumab 210 mg subcutaneous injection every 4 weeks to all 10 participants

Biological: Tezepelumab

Interventions

Tezepelumab BIOLOGICAL

10 patients will receive teszpire

Also known as: Teszpire

Tezepelumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be ≥19 of age at the time of signing the informed consent form
• Capable of giving signed informed consent.
• Having CRSwNP based on clinical symptoms and/or radiographic or endoscopic evidence of inflammation in their upper airways (Diagnosis consistent with EPOS 2020)(2)and severe asthma:
• SA based on GINA criteria (37) and confirmed with spirometry and assessmenton the previous history of asthma (a pre-post bronchodilator spirometry ormethacholine challenge to document the positive or negative history of asthmawill be performed if there is no clinical record).
• Nasal polyp score (NPS) of at least 2 on each side
• Females of childbearing potential must commit using an acceptable method of birthcontrol for the duration of the study and they must have a negative urine pregnancy test ateach study visit
• Not expecting to have surgery within the next 7 months

You may not qualify if:

• Have previously undergone sinus surgery or nasal polypectomy
• A history of organ transplantation such as lung transplantation
• Previously or currently using immunomodulator medications or antihistamines
• A history of auto-immune diseases
• Current or past sinonasal or bronchial tumors
• Currently using systemic or oral corticosteroids
• Women who are pregnant, plan to become pregnant, or breastfeed during the trial
• Current participation in any other interventional treatment trials
• Compliance: is unlikely to comply with study visits based on investigator judgment:
• Diagnosed or suspected malignant or premalignant nasal disease (e.g. SchniderianPapilloma, unilateral nasal polyposis)
• Fungal rhinosinusitis (CT/Histology), positive Aspergillus skin prick testing and/orpositive Aspergillus IgE RAST (Radioallergosorbent) testing
• Malignant neoplasm within 5 years (from screening) excluding basal cell or squamouscell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterinecervix treated locally and without metastatic disease for 3 years.
• Active bleeding disorders, and/or inability to support interruption to anticoagulant or anti-platelet therapies for nasal biopsy.
• Severe nasal deformity precluding endoscopic assessment/biopsy of postnasal space
• Have an acute or chronic infection (excluding that related to CRS) requiring managementas follows:

Sponsors & Collaborators

• Dr. Andrew Thamboo, MD: lead
• AstraZeneca: collaborator

MeSH Terms

Conditions

Asthma

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Andrew Thamboo

  St Paul's Sonis Centre Director

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Thamboo, MD

CONTACT

604-250-4174; andrew.thamboo@gmail.com

Leonora Beltran

CONTACT

604-250-4174; lbeltranjimenez@providencehealth.bc.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: The proposed design is a 24-week pilot study to investigate the histo-inflammatory and remodeling profiles and clinical outcomes of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) patients with Severe Asthma (SA) treated with Tezepelumab. The investigators plan to recruit approximately 10 subjects with (CRSwNP) and severe asthma as a "proof of concept" study. Eligible subjects will be requested to participate in the study for a maximum of 24 weeks, during which subjects will remain on their existing standard of care therapy. At Visit 2 (week 0), subjects will receive either add-on Tezepelumab (210 mg) during the 24-week treatment period. Study medication will be administered subcutaneously (SC) every 4 weeks for a total of 6 doses.

Study Record Dates

• First Submitted: August 13, 2024
• First Posted: December 18, 2024
• Study Start: January 1, 2025
• Primary Completion: March 1, 2025
• Study Completion: June 1, 2025
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share