Short Treatment With Omalizumab for Severe Asthma (SHORTEN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

20 May 2021 → ongoing

Decision date (initial)

2024-08-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Health and Solidarity

External identifiers

EU CT number

2024-513427-17-00

EudraCT number

2020-000883-42

ClinicalTrials.gov

NCT04763447

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Demonstrate the non-inferiority (i.e. no more exacerbations at 12 months) of Omalizumab withdrawal attempt compared to Omalizumab continuation in asthma-controlled patients treated for at least 33 months

Secondary objectives 14

1. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the variation in Asthma control test (ACT)
2. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the variation in Asthma quality of life (AQLQ) and St. George's Respiratory Questionnaire
3. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the variation in respiratory function
4. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the variation in mean daily dose of oral steroids (for steroid dependent patients
5. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the variation in the number of asthma controller drugs
6. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the variation in the daily dose of inhaled steroids
7. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the Time to loss of asthma control
8. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the time to the first occurence of an exacerbation
9. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the number of ermergency room visits for asthma in the year following randomization
10. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the number of hospitalisations for asthma in the year following randomization
11. Compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months at 6 and 12 months on the occurrence of deterioration in ACT.
12. Evaluate the impact of the duration of treatment with OMA and the dose of OMA before randomization on the effect of stopping treatment compared to its continuation, on (i) the number of exacerbations, (ii) the time to loss of asthma control, (iii) the ACT score, at 12 months.
13. Evaluate the impact of eosinophilia at randomization on the effect of stopping treatment, compared to its continuation, on (i) the number of exacerbations, (ii) the time to loss of asthma control, (iii) the ACT score, at 12 months.
14. Compare stopping OMA with continuing OMA on allergy symptoms (ocular, rhinitis, atopic dermatitis, food allergies) at 6 and 12 months.

Conditions and MedDRA coding

Well controlled severe allergic asthma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Adult patient >18 years old
2. Treated with OMA, prescribed by a pulmonologist, for at least 33 months for severe allergic asthma
3. Well controlled with the treatment (ACT score ⩾ 18) and having experienced no more than one exacerbation in the year preceding inclusion. An exacerbation is defined as an oral or injectable steroid course for at least 2 days and/or a minimum doubling of the usual steroid dose for at least 2 days for steroid dependent patients

Exclusion criteria 8

1. Patient refusing to stop OMA treatment, whatever the reason
2. Patient with other reason other than good asthma control to stop OMA, such as a side effect, planned or ongoing pregnancy, or planned switch to another step 5 asthma treatment (mepolizumab, benralizumab, dupilumab, reslizumab …)
3. Patient not covered by Health Insurance
4. Patient under curatorship, guardianship or safeguarding of justice
5. Patient whose adherence to asthma treatments is considered poor or questionable by the investigator
6. Patient participating in another intervention research
7. Pregnant or lactating patient
8. Patient refusing to sign consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of asthma exacerbations in the year following randomization. An exacerbation is defined as an oral or injectable steroid course for at least 2 days and/or a minimum doubling of the usual steroid dose for at least 2 days for steroid dependent patients.

Secondary endpoints 15

1. Changes in asthma control test (ACT) at 6 and 12 months. ACT is a five questions self-administered standardized questionnaire. The ACT contains 5 questions that are related to the frequency of both asthma symptoms and required rescue medication use during the previous 4 weeks. The scores in the ACT range from 5 (worse control) to 25 (total control). A minimal change in 5 points for the total score is considered clinically significant.
2. Changes in asthma quality of life (AQLQ) and St. George's Respiratory Questionnaire (SGRQ) at 6 and 12 months.
3. Changes in FEV1 (in ml) at 6 and 12 months to assess respiratory function
4. Changes in daily oral steroid dose at 6 and 12 months (percentage of variations, proportion of patients increasing their dose by ≥20%, ≥50%, ≥80%)
5. Changes in the number of asthma controller drugs at 6 and 12 months
6. Changes in the mean daily dose (µg/j) of inhaled steroids received in the 3 previous months at 6 and 12 months
7. Time to loss of asthma control defined by the number of days between the randomization and the prescription of OMA (in the withdrawal group) or another step 5 asthma treatment (mepolizumab, benralizumab, bronchial thermoplasty...); according to the pulmonologist's choice.
8. Time to exacerbation defined by the number of days between the randomization and the first occurence of an exacerbation. An exacerbation is defined as an oral or injectable steroid course for at least 2 days and/or a minimum doubling of the usual steroid dose for at least 2 days for steroid dependent patients.
9. Number of emergency room visits for asthma in the year following randomization
10. Number of hospitalisations for asthma in the year following randomization
11. Occurrence of deterioration of the asthma control (ACT) at 6 and 12 months, defined respectively by an ACT score at 6 and 12 months lower by 5 points or more compared to the ACT score at inclusion
12. Effect of OMA treatment duration before randomization on asthma control, on time of loss of asthma and on exacerbations. The following categories will be considered: [33-48 months; 49-63 months; more than 63 months]
13. Effect of OMA dosage before randomization on asthma control, on time of loss of asthma and on exacerbations. The following categories will be considered: [150-300 mg/month]; ]300-600 mg/month];]600-900 mg/month] and ]900-1200 mg/month]
14. Effect of OMA eosinophils rate on asthma control, on time of loss of asthma and on exacerbations. The following categories will be considered: <300/mm3;≥300/mm3.
15. Occurence of allergy manifestations (conjunctivitis, rhinitis, atopic dermatitis, food allergy (oral syndrome and anaphylactic reactions)) at 6 and 12 months

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Camille TAILLE

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Camille TAILLE

Locations

1 EU/EEA country · 44 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 5 files

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

Application history

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