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Trial record 1 of 16 for:    shorten omalizumab
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Short Treatment With Omalizumab for Severe Asthma (SHORTEN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04763447
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : February 10, 2022
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

The optimal duration of the treatment by OMA remains unclear when asthma is well controlled. Data suggest that a large part of patients with well controlled asthma can discontinue OMA therapy without any asthma control deterioration or with an acceptable decrease in asthma control, therefore French experts propose that omalizumab can be given for "3 to 5 yrs if asthma remains well controlled".

The costs related to OMA are high and frequent injections represent severe constraints for patients. For all these reasons, evaluating whether shortening duration of OMA therapy is feasible while maintaining acceptable asthma control is a critical point. Therefore, the aim of this study is to evaluate asthma control after OMA discontinuation after 3 to 5 years of treatment when asthma is well controlled.


Condition or disease Intervention/treatment Phase
Asthma Other: Attempt to withdrawal OMA treatment Drug: Continuation of OMA treatment Phase 4

Detailed Description:

Omalizumab (OMA) is a monoclonal anti IgE antibody, developed for severe uncontrolled allergic asthma. Efficacy of OMA in this indication is well documented in randomized trials as well as in real life studies, reducing the number of severe exacerbations by about 50% and improving asthma control score .

However, despite commercialized since 2006 in France, the optimal duration of the treatment remains unclear when asthma is well controlled. In particular, there is no guideline to apply the "step down theory" to biologics in well controlled patients.

It seems clear that a treatment given for less than one year is associated with an early relapse of the disease. However, in a randomized controlled study including 176 patients, stopping the treatment after 5 years induced a small, but acceptable loss of control (average decrease of asthma control test (ACT) by 2.88 and 1.16 point, p= 0.18), but some patients had uncontrolled asthma when the treatment was stopped. In a smaller cohort of 49 patients in Spain who voluntarily accepted to discontinue OMA treatment after 6 years of therapy, asthma deterioration (defined by one or more exacerbation and any Asthma Control Test change during the 1st year) was observed in 24% of patients during the first year following discontinuation , with a maximal rate of 2 exacerbations/yr. After 4 years of discontinuation, 60% of patients still take advantage of the 6 yrs of treatment with OMA. A retrospective study in France found that 14/26 patients treated for at least 3 years kept the same level of control after discontinuation. All these data suggest that a large part of patients with well controlled asthma can discontinue OMA therapy without any asthma control deterioration or with an acceptable decrease in asthma control.

Inducing long term asthma remissions, rather than complete cure, is one potential goal of biologics. OMA is supposed to have disease modifying effects , explaining why there is a hope for a good asthma control being maintained after discontinuation. For this reason, French experts propose that omalizumab can be given for "3 to 5 yrs if asthma remains well controlled" . After an asthma relapse, OMA can be prescribed again theoretically, but no data regarding clinical response after a "second line" of treatment with the same biologic are available. The question of optimal treatment duration is also questioned with other biologics.

The costs related to OMA are high (estimated to 12 k€/year/patient). Frequent injections (1 subcutaneous injection every 4 weeks for the lowest dose to 4 injections every 2 weeks for the highest dose) represent severe constraints for patients, especially for the youngest ones. For all these reasons, evaluating whether shortening duration of OMA therapy is feasible while maintaining acceptable asthma control is a critical point. The main objective is to demonstrate the non-inferiority (i.e. no more exacerbations at 12 months) of OMA withdrawal attempt compared to OMA continuation in asthma-controlled patients treated for 3 to 5 years with OMA. Secondary objectives are to compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for 3 to 5 years with OMA on other asthma control features at 6 and 12 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 234 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of Omalizumab Withdrawal After a 3 Year Duration Treatment in Well Controlled Severe Allergic Asthma : a Multicentric Randomized Controlled Trial
Actual Study Start Date : May 20, 2021
Estimated Primary Completion Date : May 20, 2025
Estimated Study Completion Date : May 20, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Omalizumab

Arm Intervention/treatment
Experimental: OMA withdrawal attempt Other: Attempt to withdrawal OMA treatment
Patients will be told to stop abruptly (no progressive decrease of the dose) their Omalizumab treatment and they will not be prescribed new OMA. In case of loss of control, pulmonologist can adapt asthma treatment, as in usual care. In that case, OMA can be prescribed for a second line

Active Comparator: OMA continuation Drug: Continuation of OMA treatment

Patients will be prescribed the same dosage of Omalizumab than they received before randomization, according to their weight and total circulating IgE levels.

In case of safety concerns or loss of control, pulmonologist can modify the patient treatment regimen of OMA or other co-medications, as in usual care.





Primary Outcome Measures :
  1. Number of exacerbations [ Time Frame: 12 months ]

    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.

    They will be assessed every 6 months from patients log book, written reports of ER visits or hospitalizations, and prescriptions



Secondary Outcome Measures :
  1. Time to exacerbation [ Time Frame: 12 months ]
    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.

  2. Asthma control (ACT) [ Time Frame: 6 months ]
    Changes in asthma control test (ACT). 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.

  3. Asthma control (ACT) [ Time Frame: 12 months ]
    Changes in asthma control test (ACT). 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.

  4. 5 points-decrease of asthma control (ACT) [ Time Frame: 6 months ]
    Percentage of patients with a 5 points decrease of asthma control test (ACT) compared to baseline. 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.

  5. 5 points-decrease of asthma control (ACT) [ Time Frame: 12 months ]
    Percentage of patients with a 5 points decrease of asthma control test (ACT) compared to baseline. 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.

  6. Time to loss of asthma control [ Time Frame: 12 months ]
    Number of days between the randomization and the prescription of OMA (in the withdrawal group) or another step 5 asthma treatment (mepolizumab, benralizumab, daily oral steroids, bronchial thermoplasty); according to the pulmonologist's choice.

  7. Asthma quality of life (AQLQ) [ Time Frame: 6 months ]
    Changes in asthma quality of life (AQLQ). The AQLQ is a 32-item disease-specific questionnaire that has been designed to measure the functional impairments that are most troublesome to adults with asthma. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The overall AQLQ score is the mean response to all 32 questions. Four independent studies have established that the AQLQ has strong measurement properties and validity.

  8. Asthma quality of life (AQLQ) [ Time Frame: 12 months ]
    Changes in asthma quality of life (AQLQ). The AQLQ is a 32-item disease-specific questionnaire that has been designed to measure the functional impairments that are most troublesome to adults with asthma. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The overall AQLQ score is the mean response to all 32 questions. Four independent studies have established that the AQLQ has strong measurement properties and validity.

  9. Number of asthma controller drugs [ Time Frame: 6 months ]
    Changes in the number of asthma controller drugs

  10. Number of asthma controller drugs [ Time Frame: 12 months ]
    Changes in the number of asthma controller drugs

  11. Dose of inhaled steroids [ Time Frame: 6 months ]
    Changes in the mean daily dose of inhaled steroids received in the 3 previous months

  12. Dose of inhaled steroids [ Time Frame: 12 months ]
    Changes in the mean daily dose of inhaled steroids received in the 3 previous

  13. Dose of oral steroids [ Time Frame: 6 months ]
    Changes in the mean daily dose of oral steroids (for steroid dependent patients)

  14. Dose of oral steroids [ Time Frame: 12 months ]
    Changes in the mean daily dose of oral steroids (for steroid dependent patients)

  15. Dose of oral steroids [ Time Frame: 6 months ]
    Percentage of patients with a 20% increasing of the dose compared to baseline (for steroid dependent patients)

  16. Dose of oral steroids [ Time Frame: 12 months ]
    Percentage of patients with a 20% increasing of the dose compared to baseline (for steroid dependent patients)

  17. Dose of oral steroids [ Time Frame: 6 months ]
    Percentage of patients with a 50% increasing of the dose compared to baseline (for steroid dependent patients)

  18. Dose of oral steroids [ Time Frame: 12 months ]
    Percentage of patients with a 50% increasing of the dose compared to baseline (for steroid dependent patients)

  19. Dose of oral steroids [ Time Frame: 6 months ]
    Percentage of patients with a 80% increasing of the dose compared to baseline (for steroid dependent patients)

  20. Dose of oral steroids [ Time Frame: 12 months ]
    Percentage of patients with a 80% increasing of the dose compared to baseline (for steroid dependent patients)

  21. Allergy manifestations [ Time Frame: 6 months ]
    Occurrence of food allergy (oral syndrome and anaphylactic reactions), conjunctivitis, rhinitis, atopic dermatitis

  22. Allergy manifestations [ Time Frame: 12 months ]
    Occurrence of food allergy (oral syndrome and anaphylactic reactions), conjunctivitis, rhinitis, atopic dermatitis

  23. FEV1 [ Time Frame: 6 months ]
    Changes in FEV1

  24. FEV1 [ Time Frame: 12 months ]
    Changes in FEV1

  25. Effet of OMA treatment duration on asthma control [ Time Frame: 12 months ]
    Effet of OMA treatment duration before randomization on ACT score. The following categories will be considered: [3-4 years[; [4-5 years]

  26. Effet of OMA dosage on asthma control [ Time Frame: 12 months ]
    Effet of OMA dosage before randomization on ACT score. The following categories will be considered: [150-300 mg/month]; ]300-600 mg/month];]600-900 mg/month] and ]900-1200 mg/month]

  27. Effet of eosinophils rate on asthma control [ Time Frame: 12 months ]
    Effet of OMA eosinophils rate at randomization on ACT score. The following categories will be considered: <300/mm3;≥300/mm3.

  28. Effet of OMA treatment duration on time to loss of asthma control [ Time Frame: 12 months ]
    Effet of OMA treatment duration before randomization on time to loss of asthma control. Time to loss of asthma control is defined as the number of days between the randomization and the prescription of OMA (in the withdrawal group) or another step 5 asthma treatment (mepolizumab, benralizumab, daily oral steroids, bronchial thermoplasty); according to the pulmonologist's choice. The following categories will be considered: [3-4 years[; [4-5 years]

  29. Effet of OMA dosage on time to loss of asthma control [ Time Frame: 12 months ]
    Effet of OMA dosage before randomization on time to loss of asthma control. Time to loss of asthma control is defined as the number of days between the randomization and the prescription of OMA (in the withdrawal group) or another step 5 asthma treatment (mepolizumab, benralizumab, daily oral steroids, bronchial thermoplasty); according to the pulmonologist's choice. The following categories will be considered: [150-300 mg/month]; ]300-600 mg/month];]600-900 mg/month] and ]900-1200 mg/month]

  30. Effet of eosinophils rate on time to loss of asthma control [ Time Frame: 12 months ]
    Effet of OMA eosinophils rate at randomization on time to loss of asthma control. Time to loss of asthma control is defined as the number of days between the randomization and the prescription of OMA (in the withdrawal group) or another step 5 asthma treatment (mepolizumab, benralizumab, daily oral steroids, bronchial thermoplasty); according to the pulmonologist's choice. The following categories will be considered: <300/mm3;≥300/mm3.

  31. Effet of OMA treatment duration on exacerbations [ Time Frame: 12 months ]
    Effet of OMA treatment duration before randomization on exacerbations. 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. The following categories will be considered: [3-4 years[; [4-5 years]

  32. Effet of OMA dosage on exacerbations [ Time Frame: 12 months ]
    Effet of OMA dosage before randomization on exacerbations.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. The following categories will be considered: [150-300 mg/month]; ]300-600 mg/month];]600-900 mg/month] and ]900-1200 mg/month]

  33. Effet of eosinophils rate on exacerbations [ Time Frame: 12 months ]
    Effet of OMA eosinophils rate at randomization on exacerbations. 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.The following categories will be considered: <300/mm3;≥300/mm3.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient participating in the RAMSES cohort
  • Adult patient >18 years old
  • Treated with OMA, prescribed by a pulmonologist , for 36 to 60 months for severe allergic asthma
  • 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:

  • Patient refusing to stop OMA treatment, whatever the reason
  • 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, daily oral steroids, bronchial thermoplasty, …)
  • Patient not covered by Health Insurance
  • Patient under curatorship, guardianship or safeguarding of justice
  • Patient whose adherence to asthma treatments is considered poor or questionable by the investigator
  • Patient participating in another intervention research
  • Pregnant or lactating patient
  • Patient refusing to sign consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04763447


Contacts
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Contact: Camille TAILLE, Professor 01 40 25 68 63 ext +33 camille.taille@aphp.fr

Locations
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France
Höpital Bichat-Claude Bernard Recruiting
Paris, Île De France, France, 75018
Contact: Yannick VACHER, Chef de projet DRCI    01.44.84.17.30 ext +33    yannick.vacher@aphp.fr   
Contact: Karima BOURAYOU, Chef de projet CEPHEPI    01 42 16 75 81 ext +33    karima.bourayou@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Camille TAILLE, Professor Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04763447    
Other Study ID Numbers: APHP180614
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: February 10, 2022
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
Access Criteria: Researchers who provide a methodologically sound proposal

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
severe asthma
omalizumab
allergy
biologic
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases