Mite Asthma Pediatric Immunotherapy Trial

Allergic Rhinitis Due to House Dust Mite Clinical Trial

— MAPIT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03654976
• Other study ID #: MT-11
• Secondary ID: 2016-004363-39
• Status: Completed
• Phase: Phase 3
• Start date: February 22, 2018
• Est. completion date: May 31, 2022

Study information

• Verified date: October 2023
• Source: ALK-Abelló A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 533
• Est. completion date: May 31, 2022
• Est. primary completion date: May 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• HDM SLIT-tablet
Sublingual allergy immunotherapy tablet, for daily administration (1 tablet per day)

Other:
• Placebo
Placebo sublingual tablet, for daily administration (1 tablet per day)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
ALK-Abelló A/S

Countries where clinical trial is conducted

United States,  Bulgaria,  France,  Germany,  Hungary,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Allergic Rhinitis Symptoms	Allergic rhinitis symptoms were entered in an eDiary by the participant/caregiver in a 2-week period every 4 months, for up to 24-30 months.	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).
Other	Allergic Rhinitis Medication Use	Allergic rhinitis medication use were entered in an eDiary by the participant/caregiver in a 2-week period every 4 months, for up to 24-30 months.	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).
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)