A Study in Children and Adolescents With Birch Pollen-induced Rhinoconjunctivitis (TreeTop)

Efficacy and Safety of the SQ Tree Sublingual Immunotherapy Tablet in Children and Adolescents With Moderate to Severe Allergic Rhinitis and/or Conjunctivitis Induced by Pollen From Birch and Trees Belonging to the Birch Homologous Group

This is a clinical study in children and adolescents (5-17 years) with allergy to pollen from birch (or related trees). It compares the tree SLIT-tablet with placebo in relieving rhinoconjunctivitis symptoms during the birch/tree pollen season based on the average allergic rhinoconjunctivitis daily total combined score.

The study will also collect health-related quality of life information in the groups treated with the tree SLIT-tablet or with placebo during the pollen season.

The trial medication used is already approved to treat allergic rhinitis caused by birch/tree pollen in adults in several countries?.

Study Overview

• Status: Completed
• Conditions: Allergy
• Intervention / Treatment: Drug: Placebo; Drug: SQ tree SLIT-tablet

Detailed Description

This is a phase III, parallel-group, double-blind, placebo-controlled study to evaluate efficacy and safety of the tree SLIT-tablet in children and adolescents (5-17 years) who have rhinoconjunctivitis (with or without asthma) induced by pollen from birch trees or by trees belonging to the birch homologous group. Approximately 1000 children and adolescents will be enrolled in the trial and will receive either the tree SLIT-tablet or placebo.

The trial consists of 3 periods: a screening period, a treatment period, which includes pre-seasonal and co seasonal treatment, and a follow-up period. The duration is up to 13 months for each participant.

The trial is conducted in several European countries and in Canada.

• Study Type: Interventional
• Enrollment (Actual): 915
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Project Manager; Phone Number: +4545747576; Email: clinicaltrials@alk.net

Study Locations

• Austria
  • Vienna, Austria, A-1090
    • Medical University of Vienna
  • Vienna, Austria, 1150
    • Allergy Center Vienna West
• Belgium
  • Namur
    • Erpent, Namur, Belgium, 5101
      • Practice Dr Jean-Benoit Martinot
  • Oost-Vlandeeren
    • Gent, Oost-Vlandeeren, Belgium, 9000
      • Universitair Ziekenhuis Gent
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
• Canada
  • Québec, Canada, G1V 4W2
    • Clinique Specialisee en Allergie de la Capitale
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus Universitetshospital, Astma, Allergi- og Lungeklinikken for Born
  • Copenhagen, Denmark, 1364
    • Astma, Allergi- og Lungeklinik
  • Hellerup, Denmark, 2900
    • Gentofte Hospital Allergy Clinic
• Germany
  • Duisburg, Germany, 40225
    • HNO Praxis Dr. Uta Thieme
  • Hamburg, Germany, 22549
    • Hautarztpraxis Dr. med. Daniela Kasche
  • Heidelberg, Germany, 69120
    • HNO-Praxis am Neckar
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69126
      • Kinder- u. Jugendmedizin
    • Mannheim, Baden-Württemberg, Germany, 68161
      • Gemeinschaftspraxis für Kinder und Jugendmedizin
  • Bayern
    • Munich, Bayern, Germany, 80802
      • Klinikum rechts der Isar der TUM
  • Hessen
    • Marburg, Hessen, Germany, 35043
      • Universitätsklinikum Gießen und Marburg GmbH - Klinik für Hals-, Nasen- und Ohrenheilkunde Sektion Rhinologie und Allergologie
  • Niedersachsen
    • Osnabrück, Niedersachsen, Germany, 49074
      • Klifos - Klinische Forschung Osnabruck
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40217
      • Evangelisches Krankenhaus Düsseldorf - Klinik für Kinder- und Jugendmedizin
    • Essen, Nordrhein-Westfalen, Germany, 15355
      • ENT Research GmbH
    • Hürth, Nordrhein-Westfalen, Germany, 50354
      • Kinder- und Jugendärzte
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitatsklinikum Munster
    • Neuss, Nordrhein-Westfalen, Germany, 41469
      • Praxis Dr.J. Funck
  • Rheinland-Pfalz
    • Herxheim, Rheinland-Pfalz, Germany, 76863
      • Praxis Dr. med. Karsten Jünger
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Universitätsmedizin der JGU
    • Schweigen-Rechtenbach, Rheinland-Pfalz, Germany, 76889
      • Kinderarztpraxis Dr. med. Siegfried Simmet und Simon Traub
  • Sachsen
    • Dresden, Sachsen, Germany, 01139
      • Praxis Dr. Yury Yarin
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, 1037
    • Svábhegy Plusz Kft
  • Budapest, Hungary, 1089
    • Heim Pál Gyermekkórház
  • Budapest, Hungary, 1195
    • Kispesti Egeszsegugyi Intezet
  • Csongrád
    • Szeged, Csongrád, Hungary, 6720
      • Aranyklinika Kft
• Lithuania
  • Kaunas, Lithuania, LT-50161
    • Hospital of University of Health Sciences Kauno Klinikos
  • Vilnius, Lithuania, 8109
    • Alerginiu susirgimu diagnostikos ir gydymo centras
  • Vilnius, Lithuania, LT-06256
    • "Center of Innovative Allergology" JSC
  • Kauno Apskritis
    • Kaunas, Kauno Apskritis, Lithuania, 49387
      • JSC Ausros Medicinos Centras
    • Kaunas, Kauno Apskritis, Lithuania, LT-44269
      • "CD8 Klinika" JSC
  • Tauragės Apskritis
    • Taurage, Tauragės Apskritis, Lithuania, LT-72250
      • "Medicum centrum" JSC
  • Vilniaus Apskritis
    • Vilnius, Vilniaus Apskritis, Lithuania, LT-01118
      • "Seimos gydytojas" JSC
    • Vilnius, Vilniaus Apskritis, Lithuania, LT-08406
      • "Inlita" JSC Santara CTC
    • Vilnius, Vilniaus Apskritis, Lithuania, LT-08465
      • Allergy clinic "Perspektyvos" JSC
• Netherlands
  • Overijssel
    • Enschede, Overijssel, Netherlands, 7500KA
      • Medisch Spectrum Twente
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 CN
      • Erasmus MC - Sophia Childrens Hospital
• Poland
  • Czestochowa, Poland, 42-200
    • Centrum Medyczne Pratia Czestochowa
  • Gryfice, Poland, 72-300
    • Indywidualna Specjalistyczna Praktyka Lekarska lek. med. Elzbieta Matusz
  • Kielce, Poland, 25-355
    • ETG Kielce
  • Kraków, Poland, 30-363
    • Centrum Medyczne Plejady
  • Lublin, Poland, 20-095
    • ALERGOTEST s.c. Specjalistyczne Centrum Medyczne
  • Sucha Beskidzka, Poland, 34-200
    • Gabinet Lekarski Pediatryczno-Alergologiczny Zenon Bukowczan
  • Wroclaw, Poland, 53-201
    • "All-Med" Specjalistyczna Opieka Medyczna
  • Wroclaw, Poland, 53-201
    • Michal Bogacki DOBROSTAN
  • Wroclaw, Poland, 53-301
    • Michal Bogacki DOBROSTAN
  • Wroclaw, Poland, 53-428
    • Niepubliczny Zaklad Opieki Zdrowotnej Centrum Uslug Medycznych "PROXIMUM" Sp. z o.o.
  • Łódź, Poland, 90-141
    • SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. N.Barlickiego
  • Łódź, Poland, 90-329
    • WWCOiT im. M. Kopernika w Lodzi, Osrodek Pediatryczny im. dr J.Korczaka
  • Łódź, Poland, 90-553
    • Centrum Alergologii Prof. K. Buczyłko Spółka z o.o.
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Centrum Medyczne Pratia Bydgoszcz
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-552
      • Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna
  • Malopolskie
    • Tarnów, Malopolskie, Poland, 33-100
      • ALERGO-MED Spolka z o.o.
  • Małopolskie
    • Krakow, Małopolskie, Poland, 31-411
      • Malopolskie Centrum Alergologii
    • Kraków, Małopolskie, Poland, 30-033
      • Centrum Medyczne All-Med
    • Kraków, Małopolskie, Poland, 31-411
      • Centrum Medyczne Promed
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-879
      • Nzoz E-Vita
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-382
      • Niepubliczny Zaklad Opieki Zdrowotnej "ALERGOLOGIA", Poradnia Alergologiczna
  • Łódzkie
    • Skierniewice, Łódzkie, Poland, 96-100
      • Etg Skierniewice
  • Śląskie
    • Katowice, Śląskie, Poland, 40-338
      • Specjalist. Praktyka Lek. dr n.med. Joanna Orlicz-Widawska
  • Świętokrzyskie
    • Skarżysko-Kamienna, Świętokrzyskie, Poland, 26-110
      • NSZOZ Puls - Med Anna Bogusz, Agnieszka Musielak Sp.J.
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Public Enterprise State Scient
  • Moskva, Russian Federation, 115446
    • FGBUN" Federal Research Center for Nutrition and Biotechnology "
  • Moscow
    • Moskva, Moscow, Russian Federation, 117198
      • NRPC Pediatric Hematology, Oncology, Immunology n.a. Dmitriya Rogacheva - Multispecialty
  • Moskva
    • Moscow, Moskva, Russian Federation, 105554
      • LLC "Olla-Med"
    • Moscow, Moskva, Russian Federation, 119333
      • FGBU "Scientific center of children health" of RAMS
• Slovakia
  • Levice, Slovakia, 935-31
    • DANIMED, spol. s.r.o.
  • Martin, Slovakia, 03601
    • Univerzitna Nemocnica Martin
  • Nové Zámky, Slovakia, 940 01
    • MedKol, s.r.o.
  • Prešov, Slovakia, 080 01
    • EMED s.r.o.
  • Rimavska Sobota, Slovakia, 979 01
    • Zoll-Med s.r.o., Ambulancia klinickej imunologie a alergologie
  • Vráble, Slovakia, 952 01
    • SIMIDA s.r.o.
  • Šurany, Slovakia, 942 01
    • Ambulancia klinickej imunologie a alergologie
  • Nitriansky Kraj
    • Komárno, Nitriansky Kraj, Slovakia, 945 01
      • ALERGO H2B s.r.o.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female of any race/ethnicity aged ≥4 to <18 years on the day informed consent is obtained from the parent/caregiver; the subject must be ≥5 to <18 years old at the randomisation visit
• A documented , physician diagnosed, clinically relevant history of moderate to severe AR/C induced by birch pollen (with or without asthma) despite having received treatment with symptom-relieving medication during at least 1 previous tree pollen season for ages 4 through 6 years at screening or at least 2 previous tree pollen seasons for ages 7 through 17 years at screening
• Positive skin prick test (SPT) to Betula verrucosa at screening
• Positive specific IgE to Bet v at screening

• Presence of 1 or more of the following Allergic Rhinitis Impact on Asthma (ARIA) quality of life items due to AR/C during the previous BPS:

  1. Sleep disturbance
  2. Impairment of daily activities, leisure and/or sport
  3. Impairment of school or work
  4. Troublesome symptoms

Exclusion Criteria:

• A clinically relevant history of symptomatic seasonal AR/C caused by an allergen source, other than tree pollen from the birch homologous group, with a season overlapping the TPS
• A clinically relevant history of symptomatic perennial AR/C caused by an allergen source such as animal hair and dander to which the subject is exposed during the TPS
• Any clinical deterioration of asthma (i.e. asthma exacerbation) that resulted in emergency treatment, hospitalisation or treatment with systemic corticosteroids within 3 months prior to randomisation
• Reduced lung function at randomisation defined as forced expiratory volume in 1 second (FEV1) <70% of predicted value. For subjects with asthma, this is assessed on subject's usual asthma medication following at least a 6-hour wash-out of SABA. This criterion does not need to be fulfilled if the subject is <7 years old, cannot perform reproducible FEV1 manoeuvres despite coaching and is not considered as having a diagnosis of asthma
• Ongoing treatment with any allergy immunotherapy product
• Severe chronic oral inflammation
• A diagnosis of eosinophilic oesophagitis
• A relevant history of systemic allergic reaction e.g. anaphylaxis with cardiorespiratory symptoms, generalised urticaria or severe facial angioedema that in the opinion of the investigator may constitute an increased safety concern
• Immunosuppressive treatment (ATC code L04 or L01) within 3 months prior to the screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Gelatine (fish source), mannitol and sodium hydroxide	Drug: Placebo; Placebo
Experimental: Intervention/treatment; Sublingual allergy immunotherapy tablet, for daily administration SQ tree SLIT-tablet	Drug: SQ tree SLIT-tablet; Sublingual allergy immunotherapy tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average total combined score (rhinoconjunctivitis symptoms and medication use) during the birch pollen season	European Academy of Allergy and Clinical Immunology - values 0,1,2 (The higher score means more symptoms and more rescue medication used)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average total combined score (rhinoconjunctivitis symptoms and medication use) during the tree pollen season	European Academy of Allergy and Clinical Immunology - values 0,1,2 (The higher score means more symptoms and more rescue medication used)	6 months
Average daily symptom score during the birch pollen season	Sum of the 6 allergic rhinoconjunctivitis symptom scores; No symptoms (0), Mild symptoms (1), Moderate symptoms (2), Severe symptoms (3). Total scores will be between 0-18 (higher scores means more symptoms)	3 months
Average daily symptom score during the tree pollen season	Sum of the 6 allergic rhinoconjunctivitis symptom scores; No symptoms (0), Mild symptoms (1), Moderate symptoms (2), Severe symptoms (3). Total scores will be between 0-18 (higher scores means more symptoms)	6 months
Average daily medication score during the birch pollen season	The type and dose of rescue medication will be scored. Scores between 0-20 (the higher value means the most rescue medication used)	3 months
Average daily medication score during the tree pollen season	The type and dose of rescue medication will be scored. Scores between 0-20 (the higher value means the most rescue medication used)	6 months

Collaborators and Investigators

• Sponsor: ALK-Abelló A/S
• Collaborators: Parexel
• Investigators: Principal Investigator: Monika Gappa, Prof. MD, Evangelisches Krankenhaus Düsseldorf

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Adolescents; Children; Allergic rhinoconjunctivitis; Birch
• Other Study ID Numbers: TT-06; 2020-004372-17 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No