Clinical trial NCT03654976: Mite Asthma Pediatric Immunotherapy Trial
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Allergic Asthma Due to Dermatophagoides Farinae
Allergic Asthma Due to Dermatophagoides Pteronyssinus
Allergic Rhinitis Due to House Dust Mite
Keywords: Allergic asthma, allergic rhinitis, HDM, pediatric
Lead sponsor: ALK-Abelló A/S
Sponsor class: INDUSTRY
First posted: 2018-08-31
Enrollment: 533
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel-group
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Annualized Rate of Clinically Relevant Asthma Exacerbations
timeFrame: Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)
Secondary outcomes:
measure: Proportion of Days With Nocturnal Awakenings Due to Asthma Requiring SABA Rescue Medication
timeFrame: Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)
measure: Proportions of Days With SABA Use
timeFrame: Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)
measure: Percentage Predicted FEV1
timeFrame: Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)
measure: Global Evaluation of Allergic Asthma as Having an Improved Outcome
timeFrame: Assessment done at the end of trial visit (after 24-30 months of treatment)
measure: Global Evaluation of Allergic Rhinitis as Having an Improved Outcome
timeFrame: Assessment done at the end of trial visit (after 24-30 months of treatment)
Other outcomes:
measure: Allergic Rhinitis Symptoms
timeFrame: The efficacy assessment period for the endpoint started 4 months after treatment initiation and lasted until the end of the trial or discontinuation of treatment (up to 24-30 months of treatment).
measure: Allergic Rhinitis Medication Use
timeFrame: The efficacy assessment period for the endpoint started 4 months after treatment initiation and lasted until the end of the trial or discontinuation of treatment (up to 24-30 months of treatment).
Locations:
city: Miami
country: United States
facility: Miami Clinical Research
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Georgia
city: Ypsilanti
country: United States
facility: Respiratory Medicine Research Institute of MI
state: Michigan
city: Bangor
country: United States
facility: Private Clinic
state: Pennsylvania
city: Verona
country: United States
facility: Allergy Consultants
state: Pennsylvania
city: Boerne
country: United States
facility: TTS research
state: Texas
city: San Antonio
country: United States
facility: STAAMP Research
state: Texas
city: Plovdiv
country: Bulgaria
facility: MHAT
city: Plovdiv
country: Bulgaria
facility: UMBAL "St. Georgy"
city: Ruse
country: Bulgaria
facility: SHATPPD
city: Sevlievo
country: Bulgaria
facility: Medical Center-1-Sevlievo EOOD
city: Sofia
country: Bulgaria
facility: Alitera-Med-Medical Center EOOD
city: Sofia
country: Bulgaria
facility: MBAL Tokuda Hospital Sofia
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior
city: Stara Zagora
country: Bulgaria
facility: DCC Ritam 2010
city: Brest
country: France
facility: Hopital Augustin Morvan
city: Caen
country: France
facility: Centre Hospitalier Universitaire de Caen
city: Créteil
country: France
facility: Centre hospitalier intercommunal
city: Lille Cedex
country: France
facility: Hôpital Jeanne de Flandre
city: Paris
country: France
facility: Groupe hospitalier Armand Trousseau - La Roche Guyon
city: Bramsche
country: Germany
facility: Kinderarzt-Praxis Bramsche
city: Ludwigsfelde
country: Germany
facility: Kinderarztpraxis Ludwigsfelde
city: Wuppertal
country: Germany
facility: Kinderarztpraxis
city: Baja
country: Hungary
facility: Bajai Szent Rókus Kórház
city: Budapest
country: Hungary
facility: Heim Pal Children's Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Korhaz
city: Ráckeve
country: Hungary
facility: Szent István Rendelő és Patika
city: Szeged
country: Hungary
facility: Aranyklinika Kft
city: Białystok
country: Poland
facility: NZOZ E-Vita
city: Białystok
country: Poland
facility: Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny
city: Katowice
country: Poland
facility: Specjalistyczna Praktyka Lekarska
city: Krakow
country: Poland
facility: Centrum Medyczne PROMED
city: Kraków
country: Poland
facility: Centrum Nowoczesnych Terapii
city: Lublin
country: Poland
facility: ALERGOTEST s.c. Specjalistyczne Centrum Medyczne
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Lublinie
city: Ostrowiec Świętokrzyski
country: Poland
facility: Ostrowieckie Centrum Medyczne S.C.
city: Rzeszów
country: Poland
facility: Prywatny Gabinet Lekarski
city: Skarżysko-Kamienna
country: Poland
facility: NSZOZ Puls
city: Skierniewice
country: Poland
facility: ETG Skierniewice
city: Tarnów
country: Poland
facility: ALERGO-MED Specjalistyczna
city: Wrocław
country: Poland
facility: Dobrostan
city: Zabrze
country: Poland
facility: Specjalist.
city: Łódź
country: Poland
facility: WWCOiT
city: Kazan
country: Russian Federation
facility: Kazan State Medical University 138
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University
city: Rostov-on-Don
country: Russian Federation
facility: Clinical and Diagnostic Centre "Zdorovie"
city: Ryazan
country: Russian Federation
facility: Rayzan Regional Children Hospital
city: Saint Petersburg
country: Russian Federation
facility: LLC Kurator
city: Saint-Petersburg
country: Russian Federation
facility: City children's polyclinic #35
city: Saint-Petersburg
country: Russian Federation
facility: GBUZ "Children Municipal Polyclinic #45"
city: Saint-Petersburg
country: Russian Federation
facility: LLC ArsVite Severo-Zapad
city: Samara
country: Russian Federation
facility: GBUZ "Samarskiy oblastnoy detskiy sanatoriy "Yunost" 9-proseka
city: Samara
country: Russian Federation
facility: LLC 'ArsVitae Samara'
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Sagunto
country: Spain
facility: Hospital de Sagunto
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Santiago De Compostela
country: Spain
facility: Hospital de Conxo
city: Villarreal
country: Spain
facility: Hospital de la Plana
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital - Paediatrics Oxford Road
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: University Hospital Southampton NHS Foundation
name: Graham Roberts, MD
role: PRINCIPAL_INVESTIGATOR
References: