Using Tezepelumab to Reverse Airway Changes in Asthma

REVErsing Airway Remodelling With Tezepelumab : a Protocol for a Double-blind Randomized Controlled Trial for Patients With Asthma

This study is testing if a new asthma treatment called Tezepelumab can help improve the structure of airways in people with asthma over six months.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: University Hospital, Montpellier (other)
• Drugs / interventions: tezepelumab, immunotherapy, methotrexate
• Locations: 12 sites (Dijon and 11 other locations)
• Trial ID: NCT05651841 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effects of Tezepelumab, a monoclonal antibody targeting TSLP, on bronchial morphology in patients with asthma. It is a randomized controlled trial comparing Tezepelumab treatment to a placebo over a period of six months. The study will assess changes in bronchial wall area using computed tomography scans and will also explore the relationship between genetic expression and bronchial morphology through transcriptomic analysis. The hypothesis is that Tezepelumab can partially reverse airway remodeling in asthmatic patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 85 with physician-diagnosed asthma experiencing severe or moderate exacerbations despite optimal treatment.

Not a fit: Patients with other respiratory conditions or significant CT abnormalities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of severe asthma by reversing airway remodeling.

How similar studies have performed: Previous studies have shown positive outcomes with Tezepelumab in asthma patients, indicating potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

Admitted to screening visit:

* Minimum age: 18
* Maximum age: 85
* Able to perform an inspiratory and expiratory thoracic computed tomography (CT) scan, plus a nasal CT
* In stable condition for CT scan
* Physician-diagnosed asthma according to GINA criteria
* Disease with clinical impact: at least 1 severe or 2 moderate exacerbations in the previous 12 months despite treatment according to the best standards of care
* Maximal inhaled therapy comprising high dose ICS and at least a second controller according to GINA

Based on results of screening visit and run-in:

* Post-bronchodilator forced expiratory volume in 1 second (FEV1) predicted values must be at 25-90%
* Asthma Control Questionnaire 6 (ACQ6) \> 1.5
* Oral corticosteroid maintenance therapy (if used) ≤7.5 mg/day
* On CT scan, the average percentage wall area index at the B1 and B8 bronchi (generation 3, 4, 5) is \>65%

Exclusion Criteria:

* CT abnormalities evocative of any respiratory condition other than asthma
* Treatment regimen discordant with best practices
* Pulmonary disease other than asthma requiring treatment during the previous 12 months
* A smoking history of \>20 pack years
* Receipt of any marketed or investigational biologic agent§ within 3 months or 5 halflives (whichever is longer) prior to randomization or receipt of any investigational non biologic agent within 30 days or 5 half-lives (whichever is longest) prior to randomization or receipt of live attenuated vaccines 30 days prior to the date of randomization. Participants enrolled in current or previous tezepelumab studies will not be included. Participants on previous biologics treatment are allowed to enter the study provided the appropriate washout period is fulfilled.
* Absence of signed consent
* Non-beneficiary of the French social security, single-payer health insurance system
* Presence of any condition (physical, psychological or other) that might, in the investigator's opinion, hinder study performance
* The patient is unavailable or unwilling to participate in future visits
* Potential interference from other studies
* Protected populations according to the French public health code
* Male or female patients seeking to conceive a child
* Women of childbearing potential and fertile men not using birth control method
* Pregnant, breastfeeding or lactating women
* History of a clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with antibiotics or antiviral medications finalised \< 2 weeks before randomization. Patients with preexisting serious infections should be treated before initiating therapy with tezepelumab.
* A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy.
* Patients using vaping products, including electronic cigarettes (because may induce abnormality at CT scan).
* Bronchial thermoplasty in the last 12 months prior to Visit 1.
* History of documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy.
* History of known immunodeficiency disorder including a positive human immunodeficiency virus test or the participant taking antiretroviral medications as determined by medical history and/or participant's verbal report.
* Receipt of the T2 cytokine inhibitor Suplatast tosilate within 15 days prior to randomization.
* Treatment with systemic immunosuppressive/immunomodulating drugs (eg, methotrexate, cyclosporine, etc.), except for OCS used in the treatment of asthma/asthma exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior to randomization.
* Receipt of immunoglobulin or blood products within 30 days prior to randomization.
* Receipt of allergen immunotherapy not stable within 30 days prior to randomization or with anticipated change during the treatment period.

Where this trial is running

Dijon and 11 other locations

• CHU Dijon — Dijon, France (RECRUITING)
• CHU Grenoble Alpes La Tronche — Grenoble, France (RECRUITING)
• APHP Bicêtre — Le Kremlin-Bicêtre, France (RECRUITING)
• CHRU Lille — Lille, France (WITHDRAWN)
• Hôpital de la Croix Rousse — Lyon, France (RECRUITING)
• Hôpital Nord Marseille — Marseille, France (RECRUITING)
• CHU de Montpelier — Montpellier, France (RECRUITING)
• APHP Bichat — Paris, France (RECRUITING)
• Hôpital Foch — Paris, France (RECRUITING)
• Hôpital Haut-Lévêque — Pessac, France (RECRUITING)
• CHRU Strasbourg — Strasbourg, France (RECRUITING)
• CHU Toulouse — Toulouse, France (RECRUITING)

Study contacts

• Study coordinator: Arnaud Bourdin, MD

Conditions: Airway Remodelling, Asthmatic, exacerbating asthma, Severe asthma, Airway Remodelling