REVERT : REVErsing airway Remodelling with Tezepelumab

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

27 Mar 2023 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca

External identifiers

EU CT number

2024-513195-18-00

EudraCT number

2022-002891-35

ClinicalTrials.gov

NCT05651841

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare the change-from-baseline in the average percentage bronchial wall area (%WA = (wall area (mm2)/ (wall area (mm2) + lumen area (mm2)))×100) on CT scan for patients with asthma and undergoing 6 months of tezepelumab treatment with a similar population treated via placebo

Secondary objectives 8

1. Study arms will be compared in terms of changes in radiomics (CT-scan data)
2. Study arms will be compared in terms of changes in exacerbation rates and lung function
3. Study arms will be compared in terms of changes in serum club cell secretory protein (CCSP)
4. Study arms will additionally be compared in terms of changes in nasal single-cell transcriptomic signatures
5. Continued treatment effects associated with longer treatment (12 months) will be quantified
6. Remanence after treatment stopping at 6 months will be quantified
7. The capacity of baseline data to predict the response to tezepelumab will be explored
8. Exploratory component designed to characterize the physiological repair environment will be performed

Conditions and MedDRA coding

Severe asthma

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Minimum age: 18
2. Maximum age: 85
3. Able to perform an inspiratory and expiratory thoracic computed tomography (CT) scan, plus a nasal CT
4. In stable condition for CT scan
5. Physician-diagnosed asthma according to GINA criteria
6. 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
7. Maximal inhaled therapy comprising high dose ICS and at least a second controller according to GINA
8. 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%
9. Based on results of screening visit and run-in: Asthma Control Questionnaire 6 (ACQ6) > 1.5
10. Based on results of screening visit and run-in: Oral corticosteroid maintenance therapy (if used) is 7.5 mg/day
11. Based on results of screening visit and run-in: On CT scan, the average percentage wall area index at the B1 and B8 bronchi (generation 3, 4, 5) is >65%

Exclusion criteria 24

1. CT abnormalities evocative of any respiratory condition other than asthma
2. Treatment regimen discordant with best practices
3. Pulmonary disease other than asthma‡ requiring treatment during the previous 12 months
4. A smoking history of >20 pack years
5. Receipt of any marketed or investigational biologic agent within 3 months or 5 half-lives (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.
6. Absence of signed consent
7. Non-beneficiary of the French social security, single-payer health insurance system
8. Presence of any condition (physical, psychological or other) that might, in the investigator’s opinion, hinder study performance
9. The patient is unavailable or unwilling to participate in future visits
10. Potential interference from other studies
11. Protected populations according to the French public health code
12. Male or female patients seeking to conceive a child
13. Women of childbearing potential and fertile men not using birth control method
14. Pregnant, breastfeeding or lactating women
15. 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 pre-existing serious infections should be treated before initiating therapy with tezepelumab
16. 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
17. Patients using vaping products, including electronic cigarettes (because may induce abnormality at CT scan)
18. Bronchial thermoplasty in the last 12 months prior to Visit 1
19. History of documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy
20. 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
21. Receipt of the T2 cytokine inhibitor Suplatast tosilate within 15 days prior to randomization
22. 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
23. Receipt of immunoglobulin or blood products within 30 days prior to randomization
24. Receipt of allergen immunotherapy not stable within 30 days prior to randomization or with anticipated change during the treatment period

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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 between baseline and 6 months

Secondary endpoints 46

1. Comparaison on CT-scan the change in mean %WA between arms between baseline and 12 months
2. 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
3. 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
4. Comparaison on CT-scan the change in wall area at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months
5. Comparaison on CT-scan the change in lumen area at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months
6. Comparaison on CT-scan the change in ratio wall area (WA) / lumen area(LM) at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months
7. Comparaison on CT-scan the change in lumen diameter at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months
8. Comparaison on CT-scan the change in lumen circularity at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months
9. 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 between baseline and 6 months
10. 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 between baseline and 6 months
11. Change in the expiratory to inspiration ratio of mean lung density (MLDe/i) at Baseline, 6 months and 12 months
12. Quantitative computed tomography measurements to evaluate airflow obstruction at Baseline, 6 months and 12 months
13. Change in Total small Airway Count (TAC) between Baseline and 6 months
14. Change in Total small Airway Count (TAC) between Baseline and 12 months
15. Change in Lund Mackay score between Baseline and 6 months
16. Change in Lund Mackay score between Baseline and 12 months
17. Change in Presence/absence of nasal polyposis between Baseline and 6 months
18. Change in Presence/absence of nasal polyposis between Baseline and 12 months
19. Change in Annualized exacerbation rates between Baseline and 12 months
20. Change in Days alive and not exacerbating between Baseline and 12 months
21. Change in Days alive and not hospitalized between Baseline and 12 months
22. Change in forced expiratory volume in 1 second between Baseline and 6 months
23. Change in forced expiratory volume in 1 second between Baseline and 12 months
24. Change in forced vital capacity between Baseline and 6 months
25. Change in forced vital capacity between Baseline and 12 months
26. Change in forced expiratory volume in 1 second / forced vital capacity Ratio between Baseline and 6 months
27. Change in forced expiratory volume in 1 second / forced vital capacity Ratio between Baseline and 12 months
28. Change in total lung capacity between Baseline and 6 months
29. Change in total lung capacity between Baseline and 12 months
30. Change in residual volume between Baseline and 6 months
31. Change in residual volume between Baseline and 12 months
32. Change in total lung capacity (TLC)/ residual volume(RV) ratio between Baseline and 6 months
33. Change in total lung capacity (TLC)/ residual volume(RV) ratio between Baseline and 12 months
34. Change in mean ACQ (Asthma Control Questionnaire)-6 score between Baseline and 6 months
35. Change in mean ACQ (Asthma Control Questionnaire)-6 score between Baseline and 12 months
36. Change in Breathlessness, Cough and Sputum Scale (BCSS) between Baseline and 6 months
37. Change in Breathlessness, Cough and Sputum Scale (BCSS) between Baseline and 12 months
38. Change in Sino Nasal Outcome Test 22 between Baseline and 6 months
39. Change in Sino Nasal Outcome Test 22 between Baseline and 12 months
40. Change in St George Respiratory Questionnaire (SGRQ) between Baseline and 6 months
41. Change in St George Respiratory Questionnaire (SGRQ) between Baseline and 12 months
42. Change in ECRHS III Main Questionnaire between Baseline and 6 months
43. Change in ECRHS III Main Questionnaire between Baseline and 12 months
44. Changes in serum Club cell secretory protein (CCSP) between baseline and 6 months
45. Changes in serum Club cell secretory protein (CCSP) between baseline and 12 months
46. Number of adverse event between arms between baseline and 6 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Montpellier

Sponsor organisation

Centre Hospitalier Universitaire De Montpellier

Address

Pavillon 32, 39 Avenue Charles Flahault 39 Avenue Charles Flahault

City

Montpellier Cedex 5

Postcode

34295

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Arnaud BOURDIN

Public contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Arnaud BOURDIN

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications