Clinical trial NCT04763447: Short Treatment with Omalizumab for Severe Asthma
Official title: Impact of Omalizumab Withdrawal After a 3 Year Duration Treatment in Well Controlled Severe Allergic Asthma : a Multicentric Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Asthma
Keywords: severe asthma
omalizumab
allergy
biologic
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-02-21
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 at least 33 months of treatment when asthma is well controlled.

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 at least 33 months with OMA. Secondary objectives are to compare OMA withdrawal attempt versus OMA continuation in asthma-controlled patients treated for at least 33 months with OMA on other asthma control features at 6 and 12 months.

Eligibility criteria: Inclusion Criteria:

* Adult patient \>18 years old
* Treated with OMA, prescribed by a pulmonologist , for at least 33 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

Primary outcomes:
measure: Number of exacerbations
timeFrame: 12 months
Secondary outcomes:
measure: Time to exacerbation
timeFrame: 12 months
measure: Asthma control (ACT)
timeFrame: 6 months
measure: Asthma control (ACT)
timeFrame: 12 months
measure: 5 points-decrease of asthma control (ACT)
timeFrame: 6 months
measure: 5 points-decrease of asthma control (ACT)
timeFrame: 12 months
measure: Time to loss of asthma control
timeFrame: 12 months
measure: Asthma quality of life (AQLQ)
timeFrame: 6 months
measure: Asthma quality of life (AQLQ)
timeFrame: 12 months
measure: Number of asthma controller drugs
timeFrame: 6 months
measure: Number of asthma controller drugs
timeFrame: 12 months
measure: Dose of inhaled steroids
timeFrame: 6 months
measure: Dose of inhaled steroids
timeFrame: 12 months
measure: Dose of oral steroids
timeFrame: 6 months
measure: Dose of oral steroids
timeFrame: 12 months
measure: Patients increasing their dose of oral steroids of 20%
timeFrame: 6 months
measure: Patients increasing their dose of oral steroids of 20%
timeFrame: 12 months
measure: Patients increasing their dose of oral steroids of 50%
timeFrame: 6 months
measure: Patients increasing their dose of oral steroids of 50%
timeFrame: 12 months
measure: Patients increasing their dose of oral steroids of 80%
timeFrame: 6 months
measure: Patients increasing their dose of oral steroids of 80%
timeFrame: 12 months
measure: Allergy manifestations
timeFrame: 6 months
measure: Allergy manifestations
timeFrame: 12 months
measure: FEV1
timeFrame: 6 months
measure: FEV1
timeFrame: 12 months
measure: Effect of OMA treatment duration on asthma control
timeFrame: 12 months
measure: Effect of OMA dosage on asthma control
timeFrame: 12 months
measure: Effect of eosinophils rate on asthma control
timeFrame: 12 months
measure: Effect of OMA treatment duration on time to loss of asthma control
timeFrame: 12 months
measure: Effect of OMA dosage on time to loss of asthma control
timeFrame: 12 months
measure: Effect of eosinophils rate on time to loss of asthma control
timeFrame: 12 months
measure: Effect of OMA treatment duration on exacerbations
timeFrame: 12 months
measure: Effect of OMA dosage on exacerbations
timeFrame: 12 months
measure: Effect of eosinophils rate on exacerbations
timeFrame: 12 months
measure: Hospitalisation for asthma
timeFrame: 12 months
measure: Emergency room visits for asthma
timeFrame: 12 months
measure: St. George's Respiratory Questionnaire (SGRQ)
timeFrame: 6 months
measure: St. George's Respiratory Questionnaire (SGRQ)
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Bichat-Claude Bernard
state: Île de France
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Camille TAILLE, Professor
role: PRINCIPAL_INVESTIGATOR
References: