Mite Asthma Pediatric Immunotherapy Trial

Phase 3

Completed

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

Interventions: Biological: HDM SLIT-tablet
Other: Placebo

Registration Number: NCT03654976

Lead Sponsor: ALK-Abelló A/S

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 533

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active treatment	HDM SLIT-tablet	Subject's ICS or ICS/LABA background medication plus HDM SLIT-tablet
Placebo	Placebo	Subject's ICS or ICS/LABA background medication plus placebo oral tablet

Primary Outcome Measures

Name	Time	Method
Annualized Rate of Clinically Relevant Asthma Exacerbations	Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)	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.

Secondary Outcome Measures

Name	Time	Method
Global Evaluation of Allergic Asthma as Having an Improved Outcome	Assessment done at the end of trial visit (after 24-30 months of treatment)	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.
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)	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.
Proportions of Days With SABA Use	Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)	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.
Global Evaluation of Allergic Rhinitis as Having an Improved Outcome	Assessment done at the end of trial visit (after 24-30 months of treatment)	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.
Percentage Predicted FEV1	Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)	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.

Trial Locations

Locations (64): Alitera-Med-Medical Center EOOD
🇧🇬
Sofia, Bulgaria
Specjalistyczna Praktyka Lekarska
🇵🇱
Katowice, Poland
Hospital Universitario Vall d'Hebrón
🇪🇸
Barcelona, Spain
MHAT
🇧🇬
Plovdiv, Bulgaria
MBAL Tokuda Hospital Sofia
🇧🇬
Sofia, Bulgaria
ALERGOTEST s.c. Specjalistyczne Centrum Medyczne
🇵🇱
Lublin, Poland
WWCOiT
🇵🇱
Łódź, Poland
Medical Center Excelsior
🇧🇬
Sofia, Bulgaria
UMBAL "St. Georgy"
🇧🇬
Plovdiv, Bulgaria
TTS research
🇺🇸
Boerne, Texas, United States
Kanizsai Dorottya Korhaz
🇭🇺
Nagykanizsa, Hungary
Medical Center-1-Sevlievo EOOD
🇧🇬
Sevlievo, Bulgaria
Bajai Szent Rókus Kórház
🇭🇺
Baja, Hungary
Szent István Rendelő és Patika
🇭🇺
Ráckeve, Hungary
Centre hospitalier intercommunal
🇫🇷
Créteil, France
NZOZ E-Vita
🇵🇱
Białystok, Poland
Aranyklinika Kft
🇭🇺
Szeged, Hungary
Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny
🇵🇱
Białystok, Poland
Hospital Regional Universitario de Málaga
🇪🇸
Málaga, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸
Badalona, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸
Santander, Spain
Kinderarztpraxis
🇩🇪
Wuppertal, Germany
Semmelweis Egyetem
🇭🇺
Budapest, Hungary
Miami Clinical Research
🇺🇸
Miami, Florida, United States
Columbus Regional Research Institute
🇺🇸
Columbus, Georgia, United States
Respiratory Medicine Research Institute of MI
🇺🇸
Ypsilanti, Michigan, United States
Private Clinic
🇺🇸
Bangor, Pennsylvania, United States
Allergy Consultants
🇺🇸
Verona, Pennsylvania, United States
SHATPPD
🇧🇬
Ruse, Bulgaria
Centre Hospitalier Universitaire de Caen
🇫🇷
Caen, France
Hopital Augustin Morvan
🇫🇷
Brest, France
Hôpital Jeanne de Flandre
🇫🇷
Lille Cedex, France
DCC Ritam 2010
🇧🇬
Stara Zagora, Bulgaria
Groupe hospitalier Armand Trousseau - La Roche Guyon
🇫🇷
Paris, France
Kinderarzt-Praxis Bramsche
🇩🇪
Bramsche, Germany
Kinderarztpraxis Ludwigsfelde
🇩🇪
Ludwigsfelde, Germany
Centrum Medyczne PROMED
🇵🇱
Krakow, Poland
Uniwersytecki Szpital Dzieciecy w Lublinie
🇵🇱
Lublin, Poland
NSZOZ Puls
🇵🇱
Skarżysko-Kamienna, Poland
Specjalist.
🇵🇱
Zabrze, Poland
Ostrowieckie Centrum Medyczne S.C.
🇵🇱
Ostrowiec Świętokrzyski, Poland
Prywatny Gabinet Lekarski
🇵🇱
Rzeszów, Poland
ALERGO-MED Specjalistyczna
🇵🇱
Tarnów, Poland
Kazan State Medical University 138
🇷🇺
Kazan, Russian Federation
Dobrostan
🇵🇱
Wrocław, Poland
LLC Kurator
🇷🇺
Saint Petersburg, Russian Federation
First Moscow State Medical University
🇷🇺
Moscow, Russian Federation
Clinical and Diagnostic Centre "Zdorovie"
🇷🇺
Rostov-on-Don, Russian Federation
Rayzan Regional Children Hospital
🇷🇺
Ryazan, Russian Federation
City children's polyclinic #35
🇷🇺
Saint-Petersburg, Russian Federation
GBUZ "Children Municipal Polyclinic #45"
🇷🇺
Saint-Petersburg, Russian Federation
GBUZ "Samarskiy oblastnoy detskiy sanatoriy "Yunost" 9-proseka
🇷🇺
Samara, Russian Federation
LLC ArsVite Severo-Zapad
🇷🇺
Saint-Petersburg, Russian Federation
Siberian State Medical University
🇷🇺
Tomsk, Russian Federation
Hospital de Sagunto
🇪🇸
Sagunto, Spain
Hospital de la Plana
🇪🇸
Villarreal, Spain
Hospital de Conxo
🇪🇸
Santiago De Compostela, Spain
Southampton General Hospital
🇬🇧
Southampton, United Kingdom
ETG Skierniewice
🇵🇱
Skierniewice, Poland
Centrum Nowoczesnych Terapii
🇵🇱
Kraków, Poland
LLC 'ArsVitae Samara'
🇷🇺
Samara, Russian Federation
STAAMP Research
🇺🇸
San Antonio, Texas, United States
Heim Pal Children's Hospital
🇭🇺
Budapest, Hungary
Royal Manchester Children's Hospital - Paediatrics Oxford Road
🇬🇧
Manchester, United Kingdom