Airway Remodelling, AsthmaticPhase 3REVERTNCT05651841
REVErsing Airway Remodelling With Tezepelumab
A Phase 3 study testing Tezepelumab in people with Airway Remodelling, Asthmatic, run by University Hospital, Montpellier at 11 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Airway Remodelling, Asthmatic
- What is being tested?
- Tezepelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 11 sitesFrance
- Study dates
- 27 Mar 2023to 23 Jun 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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%
Who cannot join
- 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
Show all 24Show fewer
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
France11 sites
CHU Dijon
Dijon
CHU Grenoble Alpes La Tronche
Grenoble
APHP Bicêtre
Le Kremlin-Bicêtre
Hôpital de la Croix Rousse
Lyon
Hôpital Nord Marseille
Marseille
CHU de Montpelier
Montpellier
APHP Bichat
Paris
Hôpital Foch
Paris
Hôpital Haut-Lévêque
Pessac
CHRU Strasbourg
Strasbourg
CHU Toulouse
Toulouse
About this study
Official title: REVErsing Airway Remodelling With Tezepelumab : a Protocol for a Double-blind Randomized Controlled Trial for Patients With Asthma
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
Read the detailed description
Tezepelumab is a human IgG2l monoclonal antibody (mAb) directed against TSLP. Double-blind, randomized controlled trials comparing Tezepelumab treatment against placebo demonstrate net positive benefits in asthma patients. Animal research currently indicates that blocking TSLP can prevent bronchial remodelling in murine models (Chen et al. 2013), but no such observations have been attempted in humans. Within this context, 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.
The primary objective of this protocol is therefore to compare the change-from-baseline in the average percentage bronchial wall area (%WA = (wall area (mm2)/ (wall area (mm2) + lumen area (mm2)))×100) for patients with asthma and undergoing 6 months of tezepelumab treatment with a similar population treated via placebo. Secondarily, continued treatment effects associated with longer treatment (12 months) or remanence after treatment stopping at 6 months will also be quantified. Study arms will additionally be compared in terms of:
- Changes in radiomics (CT-scan data);
- Changes in exacerbation rates and lung function;
- Changes in serum club cell secretory protein (CCSP);
- Changes in nasal single-cell transcriptomic signatures.
This study also has an exploratory component designed to characterize the physiological repair environment. In depth radiomic and transcriptomic (including single-cell analyses) profiling will be performed. Finally, the capacity of baseline data to predict the response to tezepelumab will also be explored.
- Conditions
- Airway Remodelling, Asthmatic
- Being tested
- Tezepelumab, placebo
- Keywords
- exacerbating asthma, Severe asthma, Airway Remodelling
- Medical subject headings
- Airway Remodeling, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TezepelumabDrug
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.
placeboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Tezepelumab; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Between baseline and 6 months
Secondary outcomes (46)
compare on CT-scan the change in mean %WA between arms
%WA = (wall area (mm2)/ (wall area (mm2) + lumen area (mm2)))×100) at bronchial levels likely to be affected.
Measured: 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
%WT = (wall thickness (mm) / airway diameter (mm))×100
Measured: 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
%WT = (wall thickness (mm) / airway diameter (mm))×100
Measured: 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
lumen area (mm²)
Measured: 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
lumen area (mm²)
Measured: Between baseline and 6 months
compare on CT-scan the change in ratio wall area (WA) / lumen area(LM) at the B1 and B8 bronchi, generations 3, 4 and 5
WA/LA = WA(mm²)/LA(mm²)
Measured: Between baseline and 6 months
compare on CT-scan the change in lumen diameter at the B1 and B8 bronchi, generations 3, 4 and 5
lumen diameter (mm)
Measured: Between baseline and 6 months
compare on CT-scan the change in lumen circularity at the B1 and B8 bronchi, generations 3, 4 and 5
lumen circularity (4pi x area x perimeter-²)
Measured: Between baseline and 6 months
Comparaison on CT-scan in the average percentage bronchial wall area(%WA) corrected by body surface area(BSA) at the B1 and B8 bronchi, generations 3, 4 and 5
%WA/BSA = (wall area (mm²)/ (wall area (mm²) + lumen area (mm²))×100)/(0.007184 x weight (kg)^0.425 x height (cm) ^0.725)
Measured: Between baseline and 6 months
Comparaison on CT-scan in the average percentage bronchial wall thickness (%WT) corrected by body surface area(BSA) at the B1 and B8 bronchi, generations 3, 4 and 5
%WT/BSA = ((wall thickness (mm) / airway diameter (mm))×100)/(0.007184 x weight (kg)^0.425 x height (cm) ^0.725)
Measured: Between baseline and 6 months
Change in the expiratory to inspiration ratio of mean lung density (MLDe/i),
expiratory-to-inspiratory ratios of mean lung density (MLDe/i)
Measured: At Baseline, 6 months and 12 months
Quantitative computed tomography measurements to evaluate airflow obstruction
Mucus plugging score (MPS)
Measured: At Baseline, 6 months and 12 months
Change in Total small Airway Count (TAC)
Total small Airway Count (TAC) mesured with Quantitative computed tomography
Measured: Between Baseline and 6 months
Change in Total small Airway Count (TAC)
Total small Airway Count (TAC) mesured with Quantitative computed tomography
Measured: Between Baseline and 12 months
Change in Lund Mackay score
Each sinus group (maxillary, anterior ethmoids, posterior ethmoids, sphenoid, frontal, ostiomeatal complex) is graded between 0 and 2 (0: no abnormality; 1: partial opacification; 2: total opacification). The ostiomeatal complex is scored as "0" (not obstructed) or "2" (obstructed). A total score of 0-24 is possible, and each side can be considered separately (0-12)
Measured: Between Baseline and 6 months
Change in Lund Mackay score
Each sinus group (maxillary, anterior ethmoids, posterior ethmoids, sphenoid, frontal, ostiomeatal complex) is graded between 0 and 2 (0: no abnormality; 1: partial opacification; 2: total opacification). The ostiomeatal complex is scored as "0" (not obstructed) or "2" (obstructed). A total score of 0-24 is possible, and each side can be considered separately (0-12)
Measured: Between Baseline and 12 months
Change in Presence/absence of nasal polyposis
Nasal brushing
Measured: Between Baseline and 6 months
Change in Presence/absence of nasal polyposis
Nasal brushing
Measured: Between Baseline and 12 months
Change in Annualized exacerbation rates
The patient journal will cover exacerbations and hospitalizations.Exacerbations will be further characterized according to severity as defined by GINA. Episode data (hospitalizations, and exacerbations) will be characterized by their beginning and end dates; These data will be used to estimate annualized exacerbation rates.
Measured: Between Baseline and 12 months
Change in Days alive and not exacerbating
The patient journal will cover exacerbations and hospitalizations. Exacerbations will be further characterized according to severity as defined by GINA. Episode data (hospitalizations, and exacerbations) will be characterized by their beginning and end dates; These data will be used to estimate days alive and not exacerbating.
Measured: Between Baseline and 12 months
Change in Days alive and not hospitalized
The patient journal will cover exacerbations and hospitalizations. Episode data (hospitalizations, and exacerbations) will be characterized by their beginning and end dates; These data will be used to estimate days alive and not hospitalized (total, and for each GINA type of exacerbation).
Measured: Between Baseline and 12 months
Change in forced expiratory volume in 1 second
Pre- and post-bronchodilator spirometry (FEV1; litres and percent predicted)
Measured: Between Baseline and 6 months
Change in forced expiratory volume in 1 second
Pre- and post-bronchodilator spirometry (FEV1; litres and percent predicted)
Measured: Between Baseline and 12 months
Change in forced vital capacity
Pre- and post-bronchodilator spirometry (FVC; litres and percent predicted)
Measured: Between Baseline and 6 months
Change in forced vital capacity
Pre- and post-bronchodilator spirometry (FVC; litres and percent predicted)
Measured: Between Baseline and 12 months
Change in forced expiratory volume in 1 second / forced vital capacity Ratio
Pre- and post-bronchodilator spirometry ( FEV1/FVC ratio (litres/litres)))
Measured: Between Baseline and 6 months
Change in forced expiratory volume in 1 second / forced vital capacity Ratio
Pre- and post-bronchodilator spirometry ( FEV1/FVC ratio (litres/litres)))
Measured: Between Baseline and 12 months
Change in total lung capacity
Pre-bronchodilator plethysmography (TLC(total lung capacity ); litres and percent predicted)
Measured: Between Baseline and 6 months
Change in total lung capacity
Pre-bronchodilator plethysmography (TLC(total lung capacity ); litres and percent predicted)
Measured: Between Baseline and 12 months
Change in residual volume
Pre-bronchodilator plethysmography (RV (residual volume ); litres and percent predicted)
Measured: Between Baseline and 6 months
Change in residual volume
Pre-bronchodilator plethysmography (RV (residual volume ); litres and percent predicted)
Measured: Between Baseline and 12 months
Change in total lung capacity (TLC)/ residual volume(RV) ratio
Pre-bronchodilator plethysmography : total lung capacity (TLC)/ residual volume(RV) ratio (litres/litres)
Measured: Between Baseline and 6 months
Change in total lung capacity (TLC)/ residual volume(RV) ratio
Pre-bronchodilator plethysmography : total lung capacity (TLC)/ residual volume(RV) ratio (litres/litres)
Measured: Between Baseline and 12 months
Change in mean ACQ (Asthma Control Questionnaire)-6 score
The ACQ6 is a shortened version of the ACQ((Asthma Control Questionnaire) that assesses asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and SABA use) omitting the FEV1 measurement from the original ACQ score.
Patients are asked to recall how their asthma has been during the previous week by responding to one bronchodilator use question and 5 symptom questions.
Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and <1.5 indicate partly controlled asthma, and a score ≥1.5 indicates not well controlled asthma (Juniper et al. 2006). Individual changes of at least 0.5 are considered to be clinically meaningful.
Measured: Between Baseline and 6 months
Change in mean ACQ (Asthma Control Questionnaire)-6 score
The ACQ6 is a shortened version of the ACQ((Asthma Control Questionnaire) that assesses asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and SABA use) omitting the FEV1 measurement from the original ACQ score.
Patients are asked to recall how their asthma has been during the previous week by responding to one bronchodilator use question and 5 symptom questions.
Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and <1.5 indicate partly controlled asthma, and a score ≥1.5 indicates not well controlled asthma (Juniper et al. 2006). Individual changes of at least 0.5 are considered to be clinically meaningful.
Measured: Between Baseline and 12 months
Change in Breathlessness, Cough and Sputum Scale (BCSS)
The Breathlessness, Cough and Sputum Scale (BCSS) has undergone a vigorous validation process and is designed to assess patients' daily respiratory symptoms. Symptoms are evaluated on a 5-point Likert-type scale ranging from 0 to 4, with higher scores indicating more severe symptoms. A mean change in BCSS total score > 1.0 represents substantial symptomatic improvement, changes of approximately 0.6 can be interpreted as moderate, and changes of 0.3 can be considered small (DeVries et al. 2016; Leidy et al. 2003).
Measured: Between Baseline and 6 months
Change in Breathlessness, Cough and Sputum Scale (BCSS)
The Breathlessness, Cough and Sputum Scale (BCSS) has undergone a vigorous validation process and is designed to assess patients' daily respiratory symptoms. Symptoms are evaluated on a 5-point Likert-type scale ranging from 0 to 4, with higher scores indicating more severe symptoms. A mean change in BCSS total score > 1.0 represents substantial symptomatic improvement, changes of approximately 0.6 can be interpreted as moderate, and changes of 0.3 can be considered small (DeVries et al. 2016; Leidy et al. 2003).
Measured: Between Baseline and 12 months
Change in Sino Nasal Outcome Test 22
The SNOT-22 is a further modification of the SNOT-20 (Piccirillo et al. 2002), where the scoring has been simplified by removing the importance rating. In addition to the normal 20-item version of the SNOT, 2 additional items were measured, nasal blockage, and loss of sense of taste and smell. The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110 (higher scores indicate poorer outcomes); a MCID of 8.90 has been established.
Measured: Between Baseline and 6 months
Change in Sino Nasal Outcome Test 22
The SNOT-22 is a further modification of the SNOT-20 (Piccirillo et al. 2002), where the scoring has been simplified by removing the importance rating. In addition to the normal 20-item version of the SNOT, 2 additional items were measured, nasal blockage, and loss of sense of taste and smell. The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110 (higher scores indicate poorer outcomes); a MCID of 8.90 has been established.
Measured: Between Baseline and 12 months
Change in St George Respiratory Questionnaire (SGRQ)
The SGRQ is a 50-item patient-reported instrument developed to measure the health status of patients with obstructive airway diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition.
The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status.
Measured: Between Baseline and 6 months
Change in St George Respiratory Questionnaire (SGRQ)
The SGRQ is a 50-item patient-reported instrument developed to measure the health status of patients with obstructive airway diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition.
The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status.
Measured: Between Baseline and 12 months
Change in ECRHS III Main Questionnaire
The European Community Respiratory Health Survey (ECRHS) III Main questionnaire is a survey used to track changing respiratory situations within the general population for epidemiological purposes. The questionnaire is composed of 32 pages and 105 questions. For the purposes of the present study, only the questions 21-28 will be used. Each selected question will be used as a stand-alone variable.
The advantage of using these questions is that study distributions and longitudinal change in results can be compared to previously published epidemiological results for the general population
Measured: Between Baseline and 6 months
Change in ECRHS III Main Questionnaire
The European Community Respiratory Health Survey (ECRHS) III Main questionnaire is a survey used to track changing respiratory situations within the general population for epidemiological purposes. The questionnaire is composed of 32 pages and 105 questions. For the purposes of the present study, only the questions 21-28 will be used. Each selected question will be used as a stand-alone variable.
The advantage of using these questions is that study distributions and longitudinal change in results can be compared to previously published epidemiological results for the general population
Measured: Between Baseline and 12 months
Changes in serum Club cell secretory protein (CCSP)
Changes in serum Club cell secretory protein (CCSP), an emerging blood marker associated with pulmonary function and cellular cross-talk
Measured: Between baseline and 6 months
Changes in serum Club cell secretory protein (CCSP)
Changes in serum Club cell secretory protein (CCSP), an emerging blood marker associated with pulmonary function and cellular cross-talk
Measured: Between baseline and 12 months
Number of adverse event between arms
Measured: Between baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2022
- Study start27 Mar 2023
- Primary completion31 Jan 2026
- Study completion23 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Airway Remodelling, AsthmaticStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05651841
- Sponsor's protocol ID
- RECHMPL22_0123
- Acronym
- REVERT
- Status last verified
- Jul 2026
- First submitted
- 7 Dec 2022
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REVErsing Airway Remodelling With Tezepelumab : a Protocol for a Double-blind Randomized Controlled Trial for Patients With Asthma
- ClinicalTrials.gov ID
- NCT05651841
- Acronym / sponsor ID
- REVERT / RECHMPL22_0123
- Conditions
- Airway Remodelling, Asthmatic
- Keywords
- exacerbating asthma, Severe asthma, Airway Remodelling
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 27 Mar 2023 (actual)
- Primary completion
- 31 Jan 2026 (actual)
- Study completion
- 23 Jun 2026 (actual)
- First posted
- 15 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Tezepelumab is a human IgG2l monoclonal antibody (mAb) directed against TSLP. Double-blind, randomized controlled trials comparing Tezepelumab treatment against placebo demonstrate net positive benefits in asthma patients. Animal research currently indicates that blocking TSLP can prevent bronchial remodelling in murine models (Chen et al. 2013), but no such observations have been attempted in humans. Within this context, 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.
The primary objective of this protocol is therefore to compare the change-from-baseline in the average percentage bronchial wall area (%WA = (wall area (mm2)/ (wall area (mm2) + lumen area (mm2)))×100) for patients with asthma and undergoing 6 months of tezepelumab treatment with a similar population treated via placebo. Secondarily, continued treatment effects associated with longer treatment (12 months) or remanence after treatment stopping at 6 months will also be quantified. Study arms will additionally be compared in terms of:
- Changes in radiomics (CT-scan data);
- Changes in exacerbation rates and lung function;
- Changes in serum club cell secretory protein (CCSP);
- Changes in nasal single-cell transcriptomic signatures.
This study also has an exploratory component designed to characterize the physiological repair environment. In depth radiomic and transcriptomic (including single-cell analyses) profiling will be performed. Finally, the capacity of baseline data to predict the response to tezepelumab will also be explored.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo / Tezepelumab | Experimental | Drug: Tezepelumab, Other: placeboAfter 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. |
| Tezepelumab / Tezepelumab | Experimental | Drug: TezepelumabAfter 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. |
| Tezepelumab / Placebo | Experimental | Drug: Tezepelumab, Other: placeboAfter 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TezepelumabTezepelumab 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. | Drug | Placebo / Tezepelumab, Tezepelumab / Placebo, Tezepelumab / Tezepelumab |
| placeboAPFS 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. | Other | Placebo / Tezepelumab, Tezepelumab / Placebo |
Primary outcome
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
Time frame: Between baseline and 6 months
%WA = (wall area (mm²)/ (wall area (mm²) + lumen area (mm²)))×100) at bronchial levels likely to be affected.
46 secondary outcomes
compare on CT-scan the change in mean %WA between arms
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Between baseline and 6 months
compare on CT-scan the change in ratio wall area (WA) / lumen area(LM) at the B1 and B8 bronchi, generations 3, 4 and 5
Time frame: Between baseline and 6 months
compare on CT-scan the change in lumen diameter at the B1 and B8 bronchi, generations 3, 4 and 5
Time frame: Between baseline and 6 months
compare on CT-scan the change in lumen circularity at the B1 and B8 bronchi, generations 3, 4 and 5
Time frame: Between baseline and 6 months
Comparaison on CT-scan in the average percentage bronchial wall area(%WA) corrected by body surface area(BSA) at the B1 and B8 bronchi, generations 3, 4 and 5
Time frame: Between baseline and 6 months
Comparaison on CT-scan in the average percentage bronchial wall thickness (%WT) corrected by body surface area(BSA) at the B1 and B8 bronchi, generations 3, 4 and 5
Time frame: Between baseline and 6 months
Change in the expiratory to inspiration ratio of mean lung density (MLDe/i),
Time frame: At Baseline, 6 months and 12 months
Quantitative computed tomography measurements to evaluate airflow obstruction
Time frame: At Baseline, 6 months and 12 months
Change in Total small Airway Count (TAC)
Time frame: Between Baseline and 6 months
Change in Total small Airway Count (TAC)
Time frame: Between Baseline and 12 months
Change in Lund Mackay score
Time frame: Between Baseline and 6 months
Change in Lund Mackay score
Time frame: Between Baseline and 12 months
Change in Presence/absence of nasal polyposis
Time frame: Between Baseline and 6 months
Change in Presence/absence of nasal polyposis
Time frame: Between Baseline and 12 months
Change in Annualized exacerbation rates
Time frame: Between Baseline and 12 months
Change in Days alive and not exacerbating
Time frame: Between Baseline and 12 months
Change in Days alive and not hospitalized
Time frame: Between Baseline and 12 months
Change in forced expiratory volume in 1 second
Time frame: Between Baseline and 6 months
Change in forced expiratory volume in 1 second
Time frame: Between Baseline and 12 months
Change in forced vital capacity
Time frame: Between Baseline and 6 months
Change in forced vital capacity
Time frame: Between Baseline and 12 months
Change in forced expiratory volume in 1 second / forced vital capacity Ratio
Time frame: Between Baseline and 6 months
Change in forced expiratory volume in 1 second / forced vital capacity Ratio
Time frame: Between Baseline and 12 months
Change in total lung capacity
Time frame: Between Baseline and 6 months
Change in total lung capacity
Time frame: Between Baseline and 12 months
Change in residual volume
Time frame: Between Baseline and 6 months
Change in residual volume
Time frame: Between Baseline and 12 months
Change in total lung capacity (TLC)/ residual volume(RV) ratio
Time frame: Between Baseline and 6 months
Change in total lung capacity (TLC)/ residual volume(RV) ratio
Time frame: Between Baseline and 12 months
Change in mean ACQ (Asthma Control Questionnaire)-6 score
Time frame: Between Baseline and 6 months
Change in mean ACQ (Asthma Control Questionnaire)-6 score
Time frame: Between Baseline and 12 months
Change in Breathlessness, Cough and Sputum Scale (BCSS)
Time frame: Between Baseline and 6 months
Change in Breathlessness, Cough and Sputum Scale (BCSS)
Time frame: Between Baseline and 12 months
Change in Sino Nasal Outcome Test 22
Time frame: Between Baseline and 6 months
Change in Sino Nasal Outcome Test 22
Time frame: Between Baseline and 12 months
Change in St George Respiratory Questionnaire (SGRQ)
Time frame: Between Baseline and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tezepelumab in people with Airway Remodelling, Asthmatic, run by University Hospital, Montpellier at 11 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Between baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.