Mite Asthma Pediatric Immunotherapy Trial

Study Overview
=================
Brief Summary
-----------------
The trial aims to demonstrate efficacy of the House Dust Mite SLIT-tablet versus placebo as add-on treatment in children and adolescents (5-17 years) with House Dust Mite allergic asthma based on clinically relevant asthma worsening.

Detailed Description
-----------------
The trial aims to demonstrate efficacy of the HDM SLIT-tablet versus placebo as add-on treatment in children and adolescents (5-17 years) with HDM allergic asthma based on clinically relevant asthma exacerbations. Additionally, the trial will investigate if the treatment has an effect on asthma symptoms including nightly awakenings due to asthma, asthma medication use, asthma control, lung function, allergic rhinitis and allergic rhinoconjunctivitis. Finally, quality of life (QoL) for subjects and caregivers will be measured. The trial is a randomised, parallel-group, double-blind, placebo-controlled multi-national phase III trial conducted in Europe and North America. The treatment period will be approximately 2 years. Subjects will receive a written asthma action plan.

Official Title
-----------------
A Phase III Trial Evaluating the Efficacy and Safety of the House Dust Mite (HDM) Sublingual Immunotherapy (SLIT)-Tablet in Children and Adolescents (5-17 Years) With HDM Allergic Asthma

Conditions
-----------------
Allergic Asthma Due to Dermatophagoides Farinae, Allergic Asthma Due to Dermatophagoides Pteronyssinus, Allergic Rhinitis Due to House Dust Mite

Intervention / Treatment
-----------------
* Biological: HDM SLIT-tablet
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Male or female of any race/ethnicity aged 5-17 years A female subject of childbearing potential must have a negative pregnancy test and be willing to practise appropriate contraceptive methods A clinical history of HDM allergic asthma Use of low daily dose of ICS plus LABA or medium/high daily dose of ICS with or without LABA for the control of asthma symptoms A clinical history of asthma exacerbations in the past two years One or more of the following within the past 4 weeks prior to randomisation: Daytime asthma symptoms more than twice/week Any nocturnal awakening due to asthma SABA rescue medication needed for treatment of asthma symptoms Any activity limitation due to asthma Lung function measured by FEV1 ≥ 70% of predicted value or according to local requirements Clinical history of HDM AR within the last year prior to randomisation An average TCRS>0 during the baseline period Positive specific IgE (defined as ≥class 2, ≥0.70 kU/l) against D. pteronyssinus and/or D. farinae at screening Positive SPT to D. pteronyssinus and/or D. farinae at screening Subject willing and able to comply with trial protocol Exclusion Criteria: Is sensitised and regularly exposed to animal dander, molds, and/or cockroach or other perennial allergen Has experienced a life-threatening asthma attack Within the last month before the randomisation visit (visit 3), has had an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalisation, or treatment with systemic corticosteroids Within the last 3 months before the randomisation visit (visit 3) while on high dose ICS treatment, has had an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalisation, or treatment with systemic corticosteroids Any SLIT or SCIT treatment with D. pteronyssinus or D. farinae within the previous 12 months Ongoing treatment with any allergy immunotherapy product Any clinically relevant condition or chronic disease incl. malignancy that in the opinion of the investigator would interfere with the trial evaluations or the safety of the subject Has a diagnosis of eosinophilic oesophagitis A relevant history of systemic allergic reactions Ongoing treatment with OCS Treatment with restricted and prohibited concomitant medication Treatment with an investigational drug within 30 days/5 half-lives of the drug (which ever longest) prior to screening A history of allergy, hypersensitivity or intolerance to any of the excipients or active substance of the IMP (except D. pteronyssinus and D. farinae) or to any excipient of the rescue medication provided in this trial A business or personal relationship with trial staff or sponsor who is directly involved with the conduct of the trial A history of alcohol or drug abuse Has previously been randomised into this trial, is participating in this trial at another investigational site or is participating or planning to participate in any other clinical trial during the duration of this trial Has a history or current evidence of any condition, treatment, laboratory values out of range or other circumstance that in the opinion of the investigator are clinically relevant and might expose the subject to risk by participating in the trial, confound the results of the trial, or interfere with the subject's participation for the full duration of the trial Has a condition or treatment that increase the risk of the subject developing severe adverse reactions after adrenaline/epinephrine administration Is unable to or will not comply with the use of adrenaline/epinephrine auto-injectors for countries where this is a regulatory requirement

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel-group
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment<br>Subject's ICS or ICS/LABA background medication plus HDM SLIT-tablet | Biological: HDM SLIT-tablet<br>* Sublingual allergy immunotherapy tablet, for daily administration (1 tablet per day)<br>* Other names: Odactra;|
| Placebo Comparator: Placebo<br>Subject's ICS or ICS/LABA background medication plus placebo oral tablet | Other: Placebo<br>* Placebo sublingual tablet, for daily administration (1 tablet per day)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Rate of Clinically Relevant Asthma Exacerbations | The primary endpoint of the trial was the annualized rate of clinically relevant asthma exacerbations calculated as the number of exacerbations per year per participant during the efficacy evaluation period of 20 months. A clinically relevant asthma exacerbation had to be medically confirmed and was defined as asthma worsening leading to at least 1 of the following criteria: Doubling of ICS dose compared to background treatment Systemic corticosteroids for treatment of asthma symptoms for at least 3 days Emergency room visit due to asthma, requiring systemic corticosteroids Hospitalization for more than 12 hours due to asthma, requiring treatment with systemic corticosteroids The outcome measure (by treatment group) is an adjusted annualized rate of clinically relevant asthma exacerbations. | Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Days With Nocturnal Awakenings Due to Asthma Requiring SABA Rescue Medication | The days with nocturnal awakenings due to asthma requiring SABA rescue medication were entered in an eDiary by the participant/caregiver in a 2-week period every 4 months. The proportion of days with nocturnal awakenings due to asthma requiring SABA was presented on a range from 0 to 1 (1 indicating that all days in the eDiary period were with nocturnal awakenings due to asthma requiring SABA rescue medication). The efficacy assessment was based on data collected over the 20 months efficacy assessment period. The outcome measure (by treatment group) is an estimated proportion of days with nocturnal awakenings due to asthma requiring SABA rescue medication. | Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period) | 
| Proportions of Days With SABA Use | The days with SABA use were entered in an eDiary by the participant/caregiver in a 2-week period every 4 months. The proportion of days with SABA use was presented on a range from 0 to 1 (1 indicating that all days in the eDiary period were with SABA use). The efficacy assessment was based on data collected over the 20 months efficacy assessment period. The outcome measure (by treatment group) is an estimated proportion of days with SABA use. | Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period) | 
| Percentage Predicted FEV1 | The outcome measure (by treatment) is an average of the percentage predicted FEV1 measured at visits 5 to 11 (every 4 months during the 20 months efficacy assessment period), analyzed using MMRM (mixed-effect model repeated measurement). FEV1 (forced expired volume in 1 second) is assessed by use of spirometry and is a measure for lung function. Percentage predicted FEV1 is derived from the predicted FEV1, which is the expected value of FEV1 for a person of a certain age, race, height and gender with healthy lungs. | Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period) | 
| Global Evaluation of Allergic Asthma as Having an Improved Outcome | At the end of trial visit, the subject was asked, when compared to their asthma before IMP treatment, how they felt overall. Subjects who answered 'much better' or 'better' were categorized as having improved allergic asthma. At the end of trial visit, subjects had been treated for 24-30 months (including a 4-10 months treatment initiation and maintenance period). The outcome measure (by treatment) is an adjusted odds of experiencing improved allergic asthma. | Assessment done at the end of trial visit (after 24-30 months of treatment) | 
| Global Evaluation of Allergic Rhinitis as Having an Improved Outcome | At the end of trial visit, the subject was asked, when compared to their rhinitis before IMP treatment, how they felt overall. Subjects who answered 'much better' or 'better' were categorized as having improved allergic rhinitis. At the end of trial visit, subjects had been treated for 24-30 months (including a 4-10 months treatment initiation and maintenance period). The outcome measure (by treatment) is an adjusted odds of experiencing improved allergic rhinitis. | Assessment done at the end of trial visit (after 24-30 months of treatment) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Allergic asthma, allergic rhinitis, HDM, pediatric