REVErsing Airway Remodelling With Tezepelumab

NCT05651841 | Recruiting Phase 3 DMC

• 1 other identifier: RECHMPL22_0123
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 12

Brief Summary

The aim of this protocol is to perform a first randomized controlled trial evaluating how Tezepelumab affects the bronchial morphology (and computed tomographic variables in general) of asthmatic patients. In parallel, the investigators also hope to reproduce clinical benefits and perform a transcriptomic study that will juxtapose changes in genetic expression with changes in bronchial morphology and inflammatory signatures. The general hypothesis is that tezepelumab treatment is capable of at least partially reversing bronchial remodelling as detected on computed-tomographic (CT) scans. The investigators also expect such reversal to occur within a unique physiological repair environment that will be reflected by transcriptomic profiles

Conditions

Airway Remodelling, Asthmatic

Keywords

exacerbating asthma; Severe asthma; Airway Remodelling

Outcome Measures

Primary Outcomes (1)

• Comparaison on CT-scan in the change in mean percentage bronchial wall area (%WA) at the B1 and B8 bronchi, generations 3, 4 and 5

  %WA = (wall area (mm²)/ (wall area (mm²) + lumen area (mm²)))×100) at bronchial levels likely to be affected.

  Between baseline and 6 months

Secondary Outcomes (46)

• compare on CT-scan the change in mean %WA between arms

  Between baseline and 12 months

• Comparaison on CT-scan in the average percentage bronchia wall thickness index (%WT) at the B1 and B8 bronchi, generations 3, 4 and 5

  Between baseline and 6 months

• Comparaison on CT-scan in the average percentage bronchia wall thickness index (%WT) at the B1 and B8 bronchi, generations 3, 4 and 5

  Between baseline and 12 months

• compare on CT-scan the change in wall area at the B1 and B8 bronchi, generations 3, 4 and 5

  Between baseline and 6 months

• compare on CT-scan the change in lumen area at the B1 and B8 bronchi, generations 3, 4 and 5

  Between baseline and 6 months

Study Arms (3)

Placebo / Tezepelumab

EXPERIMENTAL

After 6-months of treatment, patients initially receiving placebo will switch to Tezepelumab for an additional 6 months. For 6 months of treatment, six subcutaneous (injections in accessorized pre-filled syringes (APFS)) are performed every 4 weeks. Each subcutaneous injection corresponds to 210 mg of Tezepelumab or analogous placebo.

Drug: Tezepelumab; Other: placebo

Tezepelumab / Tezepelumab

EXPERIMENTAL

After 6-months of treatment, patients receiving Tezepelumab will continue Tezepelumab for an additional 6 months. For 6 months of treatment, six subcutaneous (injections in accessorized pre-filled syringes (APFS)) are performed every 4 weeks.Each subcutaneous injection corresponds to 210 mg of Tezepelumab.

Drug: Tezepelumab

Tezepelumab / Placebo

EXPERIMENTAL

After 6-months of treatment, patients receiving Tezepelumab will be switched to a placebo for an additional 6 months. For 6 months of treatment, six subcutaneous (injections in accessorized pre-filled syringes (APFS)) are performed every 4 weeks. Each subcutaneous injection corresponds to 210 mg of Tezepelumab or analogous placebo.

Drug: Tezepelumab; Other: placebo

Interventions

Tezepelumab DRUG

Tezepelumab is supplied as a sterile, single-use, preservation-free, clear, colourless to slightly yellow liquid for subcutaneous administration in accessorized pre-filled syringes (APFS). Injections will be performed by study staff (doctors or nurses) during face-to-face study visits in participating centres. Subcutaneous injections are performed in a different body-part following the suggested rotation diagram.

Placebo / Tezepelumab; Tezepelumab / Placebo; Tezepelumab / Tezepelumab

placebo OTHER

APFS containing analogous placebo identical in appearance: Injections will be performed by study staff (doctors or nurses) during face-to-face study visits in participating centres. Subcutaneous injections are performed in a different body-part following the suggested rotation diagram.

Placebo / Tezepelumab; Tezepelumab / Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (12)

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

MeSH Terms

Conditions

Airway Remodeling; Asthma

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Central Study Contacts

Arnaud Bourdin, MD

CONTACT

+33467336126; a-bourdin@chu-montpellier.fr

Fanny Cardon

CONTACT

+33467330824; depotac@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2022
• First Posted: December 15, 2022
• Study Start: March 27, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

FR (12)