AllergyPhase 3TreeTopNCT04878354
A Study in Children and Adolescents With Birch Pollen-induced Rhinoconjunctivitis
A Phase 3 study testing Tree SLIT-tablet in people with Allergy, run by ALK-Abelló A/S at 80 sites in 11 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Allergy
- What is being tested?
- Tree SLIT-tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 952 participants
- Where
- 80 sitesin 11 countries
- Study dates
- 7 Apr 2021to 31 Jul 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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:
- Sleep disturbance
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- Impairment of daily activities, leisure and/or sport
- Impairment of school or work
- Troublesome symptoms
Who cannot join
- 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
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- 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
Trial locations and contacts
80 sites in 11 countries.
80 sites in 11 countries
Poland24 sites
NZOZ E-Vita
Bialystok, Podlaskie Voivodeship, 15-879
Centrum Medyczne PRATIA Bydgoszcz
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796
Centrum Medyczne Pratia Czestochowa
Częstochowa, 42-200
Indywidualna Specjalistyczna Praktyka Lekarska lek. med. Elzbieta Matusz
Gryfice, 72-300
Specjalist. Praktyka Lek. dr n.med. Joanna Orlicz-Widawska
Katowice, Silesian Voivodeship, 40-338
ETG Kielce
Kielce, 25-355
Centrum Medyczne ALL-MED
Krakow, Lesser Poland Voivodeship, 30-033
Centrum Medyczne PROMED
Krakow, Lesser Poland Voivodeship, 31-411
Malopolskie Centrum Alergologii
Krakow, Lesser Poland Voivodeship, 31-411
Centrum Medyczne Plejady
Krakow, 30-363
SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. N.Barlickiego
Lodz, 90-141
WWCOiT im. M. Kopernika w Lodzi, Osrodek Pediatryczny im. dr J.Korczaka
Lodz, 90-329
Centrum Alergologii Prof. K. Buczyłko Spółka z o.o.
Lodz, 90-553
Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna
Lublin, Lublin Voivodeship, 20-552
Alergotest s.c. Specjalistyczne Centrum Medyczne
Lublin, 20-095
NSZOZ Puls - Med Anna Bogusz, Agnieszka Musielak Sp.J.
Skarżysko-Kamienna, Świętokrzyskie Voivodeship, 26-110
ETG Skierniewice
Skierniewice, Łódź Voivodeship, 96-100
Gabinet Lekarski Pediatryczno-Alergologiczny Zenon Bukowczan
Sucha Beskidzka, 34-200
Niepubliczny Zaklad Opieki Zdrowotnej "ALERGOLOGIA", Poradnia Alergologiczna
Szczecin, West Pomeranian Voivodeship, 70-382
ALERGO-MED Spolka z o.o.
Tarnów, Lesser Poland Voivodeship, 33-100
"All-Med" Specjalistyczna Opieka Medyczna
Wroclaw, 53-201
Michal Bogacki DOBROSTAN
Wroclaw, 53-201
Michal Bogacki DOBROSTAN
Wroclaw, 53-301
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Uslug Medycznych "PROXIMUM" Sp. z o.o.
Wroclaw, 53-428
Germany17 sites
Praxis Dr. Yury Yarin
Dresden, Saxony, 01139
HNO Praxis Dr. Uta Thieme
Duisburg, 40225
Evangelisches Krankenhaus Düsseldorf - Klinik für Kinder- und Jugendmedizin
Düsseldorf, North Rhine-Westphalia, 40217
ENT Research GmbH
Essen, North Rhine-Westphalia, 15355
Hautarztpraxis Dr. med. Daniela Kasche
Hamburg, 22549
Kinder- u. Jugendmedizin
Heidelberg, Baden-Wurttemberg, 69126
HNO-Praxis am Neckar
Heidelberg, 69120
Praxis Dr. med. Karsten Jünger
Herxheim, Rhineland-Palatinate, 76863
Kinder- und Jugendärzte
Hürth, North Rhine-Westphalia, 50354
Universitätsmedizin der JGU
Mainz, Rhineland-Palatinate, 55131
Gemeinschaftspraxis für Kinder und Jugendmedizin
Mannheim, Baden-Wurttemberg, 68161
Universitätsklinikum Gießen und Marburg GmbH - Klinik für Hals-, Nasen- und Ohrenheilkunde Sektion Rhinologie und Allergologie
Marburg, Hesse, 35043
Klinikum rechts der Isar der TUM
Munich, Bavaria, 80802
Universitätsklinikum Münster
Münster, North Rhine-Westphalia, 48149
Praxis Dr.J. Funck
Neuss, North Rhine-Westphalia, 41469
KliFOs - Klinische Forschung Osnabrück
Osnabrück, Lower Saxony, 49074
Kinderarztpraxis Dr. med. Siegfried Simmet und Simon Traub
Schweigen-Rechtenbach, Rhineland-Palatinate, 76889
Lithuania9 sites
JSC Ausros Medicinos Centras
Kaunas, Kaunas County, 49387
"CD8 Klinika" JSC
Kaunas, Kaunas County, LT-44269
Hospital of University of Health Sciences Kauno Klinikos
Kaunas, LT-50161
"Medicum centrum" JSC
Tauragė, Tauragė County, LT-72250
"Seimos gydytojas" JSC
Vilnius, Vilnius County, LT-01118
"Inlita" JSC Santara CTC
Vilnius, Vilnius County, LT-08406
Allergy clinic "Perspektyvos" JSC
Vilnius, Vilnius County, LT-08465
Alerginiu susirgimu diagnostikos ir gydymo centras
Vilnius, 8109
"Center of Innovative Allergology" JSC
Vilnius, LT-06256
Slovakia8 sites
ALERGO H2B s.r.o.
Komárno, Nitra Region, 945 01
DANIMED, spol. s.r.o.
Levice, 935-31
Univerzitna Nemocnica Martin
Martin, 03601
MedKol, s.r.o.
Nové Zámky, 940 01
EMED s.r.o.
Prešov, 080 01
Zoll-Med s.r.o., Ambulancia klinickej imunologie a alergologie
Rimavská Sobota, 979 01
Ambulancia klinickej imunologie a alergologie
Šurany, 942 01
SIMIDA s.r.o.
Vráble, 952 01
Hungary5 sites
Svábhegy Plusz Kft
Budapest, 1037
Semmelweis Egyetem
Budapest, 1083
Heim Pál Gyermekkórház
Budapest, 1089
Kispesti Egeszsegugyi Intezet
Budapest, 1195
Aranyklinika Kft
Szeged, Csongrád megye, 6720
Russia5 sites
LLC "Olla-Med"
Moscow, Moscow, 105554
NRPC Pediatric Hematology, Oncology, Immunology n.a. Dmitriya Rogacheva - Multispecialty
Moscow, Moscow, 117198
FGBU "Scientific center of children health" of RAMS
Moscow, Moscow, 119333
Public Enterprise State Scient
Moscow, 115478
FGBUN" Federal Research Center for Nutrition and Biotechnology "
Moskva, 115446
Belgium3 sites
Practice Dr Jean-Benoit Martinot
Erpent, Namur, 5101
Universitair Ziekenhuis Gent
Ghent, Oost-Vlandeeren, 9000
UZ Leuven
Leuven, Vlaams Brabant, 3000
Denmark3 sites
Aarhus Universitetshospital, Astma, Allergi- og Lungeklinikken for Born
Aarhus, 8200
Astma, Allergi- og Lungeklinik
Copenhagen, 1364
Gentofte Hospital Allergy Clinic
Hellerup, 2900
Austria2 sites
Allergy Center Vienna West
Vienna, 1150
Medical University of Vienna
Vienna, A-1090
Canada2 sites
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
Clinique specialisee en allergie de la capitale
Québec, G1V 4W2
Netherlands2 sites
Medisch Spectrum Twente
Enschede, Overijssel, 7500KA
Erasmus MC - Sophia Childrens Hospital
Rotterdam, South Holland, 3015 CN
About this study
Official title: 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?.
Read the 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.
- Conditions
- Allergy
- Being tested
- Tree SLIT-tablet, Placebo SLIT-tablet
- Keywords
- Allergic rhinoconjunctivitis, Children, Adolescents, Birch
- Medical subject headings
- Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tree SLIT-tabletDrug
Sublingual allergy immunotherapy tablets
Placebo SLIT-tabletDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Gelatine (fish source), mannitol and sodium hydroxide Receives: Drug: Placebo SLIT-tablet |
| Intervention/treatment | Experimental | Sublingual allergy immunotherapy tablet, for daily administration SQ tree SLIT-tablet Receives: Drug: Tree SLIT-tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Total Combined Score (TCS) During the Birch Pollen Season (BPS)
The primary endpoint of the trial was the average allergic rhinitis and/or conjunctivitis TCS during the BPS. The average TCS evaluates the treatment effect based on reduction in daily rhinoconjunctivitis symptoms and medication use (on a scale of 0-38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Secondary outcomes (32)
Average Total Combined Score (TCS) During the Tree Pollen Season (TPS)
Average TCS measured in the TPS. TPS includes hazel, alder, birch and oak pollen seasons. The average TCS evaluates the treatment effect based on reduction in daily rhinoconjunctivitis symptoms and medication use (on a scale of 0-38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the TPS (mean duration of approximately 11 weeks)
Average Daily Symptoms Score (DSS) During the Birch Pollen Season (BPS)
Average rhinoconjunctivitis DSS during the BPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Average Daily Symptoms Score (DSS) During the Tree Pollen Season (TPS)
Average rhinoconjunctivitis DSS during the TPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). TPS includes hazel, alder, birch and oak pollen seasons. Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the TPS (mean duration of approximately 11 weeks).
Average Daily Medication Score (DMS) During the Birch Pollen Season (BPS)
Average rhinoconjunctivitis DMS during the BPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Average Daily Medication Score (DMS) During the Tree Pollen Season (TPS)
Average rhinoconjunctivitis DMS during the TPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). TPS includes hazel, alder, birch and oak pollen seasons. Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the TPS (mean duration of approximately 11 weeks)
Average Total Combined Score (TCS) During the Alder Hazel Pollen Season (AHPS)
Average TCS during the AHPS evaluates the treatment effect based on reduction in daily rhinoconjunctivitis symptoms and medication use (on a scale of 0-38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the AHPS (mean duration of approximately 6-7 weeks)
Average Daily Symptoms Score (DSS) During the Alder Hazel Pollen Season (AHPS)
Average rhinoconjunctivitis DSS during the AHPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the AHPS (mean duration of approximately 6-7 weeks)
Average Daily Medication Score (DMS) During the Alder Hazel Pollen Season (AHPS)
Average rhinoconjunctivitis DMS during the AHPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the AHPS (mean duration of approximately 6-7 weeks)
Average Total Combined Score (TCS) During the Oak Pollen Season (OPS)
Average TCS measured in the OPS evaluates the treatment effect based on reduction in daily rhinoconjunctivitis symptoms and medication use (on a scale of 0-38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the OPS (mean duration of approximately 3 weeks)
Average Daily Symptoms Score (DSS) During the Oak Pollen Season (OPS)
Average rhinoconjunctivitis DSS during the OPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the OPS (mean duration of approximately 3 weeks)
Average Daily Medication Score (DMS) During the Oak Pollen Season (OPS)
Average rhinoconjunctivitis DMS during the OPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the OPS (mean duration of approximately 3 weeks)
Number of Severe Days During the Birch Pollen Season (BPS)
The disease burden for participants was analyzed in terms of proportion of severe days.
A severe day was a day with a daily symptom score (DSS) ≥6 and ≥2 moderate symptoms or 1 severe symptom. The DSS ranged from 0 to 18 and was the sum of the 6 allergic rhinoconjunctivitis symptom scores, each scored on a scale from 0 to 3 (0 = no symptoms, 1= mild symptoms, 2= moderate symptoms and 3 = severe symptoms).
The proportion of severe days was the number of severe days divided by the number of days in the season.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Number of Severe Days During the Tree Pollen Season (TPS)
The disease burden for participants was analyzed in terms of proportion of severe days.
A severe day was a day with a daily symptom score (DSS) ≥6 and ≥2 moderate symptoms or 1 severe symptom. The DSS ranged from 0 to 18 and was the sum of the 6 allergic rhinoconjunctivitis symptom scores, each scored on a scale from 0 to 3 (0 = no symptoms, 1= mild symptoms, 2= moderate symptoms and 3 = severe symptoms).
The proportion of severe days was the number of severe days divided by the number of days in the season.
Measured: During the TPS (mean duration of approximately 11 weeks)
Number of Well Days During the Birch Pollen Season (BPS)
A well day was defined as a day with no use of allergic rhinitis and/or conjunctivitis (AR/C) rescue medication (daily medication score =0) and daily symptom score ≤2.
The proportion of well days was the number of well days divided by the number of days in the season.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Number of Well Days During the Tree Pollen Season (TPS)
A well day was defined as a day with no use of allergic rhinitis and/or conjunctivitis (AR/C) rescue medication (daily medication score =0) and daily symptom score ≤2.
The proportion of well days was the number of well days divided by the number of days in the season.
Measured: During the TPS (mean duration of approximately 11 weeks)
Number of Symptom-free Days During the Birch Pollen Season (BPS)
A a symptom-free day was defined as a day with no symptoms and with no use of rescue medication (Total Combined Score = 0). The proportion of symptom-free days was the number of symptom-free divided by the number of days in the season.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Number of Symptom-free Days During the Tree Pollen Season (TPS)
A a symptom-free day was defined as a day with no symptoms and with no use of rescue medication (Total Combined Score = 0).
The proportion of symptom-free days was the number of symptom-free divided by the number of days in the season.
Measured: During the TPS (mean duration of approximately 11 weeks)
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS)
A symptom-free day was defined as a day with no symptoms and with no use of rescue medication, i.e. total combined score (TCS) =0. Thus, the endpoint was categorized as a binary variable with a subject being a responder if he/she had no symptoms and had not used rescue medication during the season
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS)
A symptom-free day was defined as a day with no symptoms and with no use of rescue medication, i.e. total combined score (TCS) = 0. Thus, the endpoint was categorized as a binary variable with a subject being a responder if he/she had no symptoms and had not used rescue medication during the tree pollen season.
Measured: During the TPS (mean duration of approximately 11 weeks)
Average Total Combined Score (TCS) (EAACI Scoring) During Birch Pollen Season (BPS)
The TCS European Academy of Allergy and Clinical Immunology (EAACI) scoring was calculated using the medication score proposed by EAACI and was the sum of the DSS/6 and the daily EAACI medication score (DMSEAACI) (values 0,1,2), and thus ranged 0-5 with higher scores indicating more combined allergy symptoms and medication use. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Average Total Combined Score (TCS) (EAACI Scoring) During Tree Pollen Season (TPS)
The TCS European Academy of Allergy and Clinical Immunology (EAACI) scoring was calculated using the medication score proposed by EAACI and was the sum of the DSS/6 and the daily EAACI medication score (DMSEAACI) (values 0,1,2), and thus ranged 0-5 with higher scores indicating more combined allergy symptoms and medication use. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the TPS (mean duration of approximately 11 weeks).
Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Birch Pollen Season (BPS) (12-17 Years Only)
The RQLQ measured the rhinoconjunctivitis quality of life. The RQLQ (for participants 12-17 years only) comprised 28 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall RQLQ score was the mean of the 28 item scores.
The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Tree Pollen Season (TPS) (12-17 Years Only)
The RQLQ measured the rhinoconjunctivitis quality of life. The RQLQ (for participants 12-17 years only) comprised 28 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall RQLQ score was the mean of the 28 item scores.
The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the TPS (mean duration of approximately 11 weeks)
Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score During the Birch Pollen Season (BPS) (5-11 Years Only)
The PRQLQ measured the paediatric rhinoconjunctivitis quality of life. The PRQLQ consisted of 23 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall PRQLQ score was the mean of the 23 item scores.
The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: During the BPS (mean duration of approximately 3-4 weeks)
Treatment Satisfaction (TSQM-9)
Treatment satisfaction was measured using the 9-item treatment satisfaction questionnaire for medication (TSQM-9 questionnaire). After ending treatment, participants completed the TSQM-9 questionnaire which consisted of 9 items covering 3 domains. Each item was scored on a 5 point (ranging 1-5) or 7 point (ranging 1-7) scale. For each domain, item scores were summed and normalised to a 0-100 scale, with higher scores indicating better satisfaction.
Measured: After ending treatment (after approximately 52 weeks of treatment)
Patient-rated Global Evaluation of Treatment Efficacy
The global evaluation measured patient treatment satisfaction. After ending treatment, participants were asked: 'Compared to your rhinitis and/or conjunctivitis symptoms in the previous birch/tree pollen season, how have you felt overall in this birch/tree pollen season?'. The endpoint was evaluated as a binary endpoint; answer options 'much better' and 'better' were categorised as improved (taking value 1), while answer options 'the same', 'worse', and 'much worse' were categorised as not improved (taking value 0).
The primary estimand for the endpoint was he trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Measured: End of treatment (after approximately 52 weeks of treatment)
Change From Baseline in Birch Specific IgE
Birch specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation
Measured: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Birch Specific IgG4
Birch specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Measured: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF)
The IgE-blocking factor assesses the effect of serum components (including IgE-blocking antibodies known to be induced by allergy immunotherapy) competing with IgE for binding to allergen. IgE-blocking factor is calculated as 1-(S/T), where S is the amount of allergen-specific IgE bound to allergen in the (possible) presence of competing components, and where T is the total amount of allergen-specific IgE capable of binding to allergen when all competing antibodies/components have been washed off. IgE-blocking factor values closer to 0 indicate the presence of fewer IgE-blocking components and values closer to 1 indicate that more IgE is blocked from binding to the allergen.
Measured: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Alder, Hazel and Oak Specific IgE
Change in alder, hazel and oak specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Measured: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Alder, Hazel and Oak Specific IgG4
Change in alder, hazel and oak specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Measured: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF)
The IgE-blocking factor assesses the effect of serum components (including IgE-blocking antibodies known to be induced by allergy immunotherapy) competing with IgE for binding to allergen. IgE-blocking factor is calculated as 1-(S/T), where S is the amount of allergen-specific IgE bound to allergen in the (possible) presence of competing components, and where T is the total amount of allergen-specific IgE capable of binding to allergen when all competing antibodies/components have been washed off. IgE-blocking factor values closer to 0 indicate the presence of fewer IgE-blocking components and values closer to 1 indicate that more IgE is blocked from binding to the allergen.
Measured: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks treatment, on average)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2021
- Study start7 Apr 2021
- Primary completion31 Jul 2023
- Study completion31 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AllergyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 952 participants (actual)
Sponsor and investigators
- Lead sponsor
- ALK-Abelló A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Monika Gappa, Prof. MD, Principal investigator, Evangelisches Krankenhaus Düsseldorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04878354
- Sponsor's protocol ID
- TT-06
- Other IDs
- 2020-004372-17
- Acronym
- TreeTop
- Status last verified
- Jan 2025
- First submitted
- 24 Mar 2021
- Last updated
- 22 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gagnon R, Dalgaard T, Ortving GS, Gappa M, Nolte H. Efficacy and safety of the tree sublingual immunotherapy tablet in the subpopulation of Canadian children with allergic rhinitis and/or conjunctivitis: phase III trial results. Allergy Asthma Clin Immunol. 2026 Jul 11. doi: 10.1186/s13223-026-01054-w. Online ahead of print.
PubMed 42432760
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04878354
- Acronym / sponsor ID
- TreeTop / TT-06
- Conditions
- Allergy
- Keywords
- Allergic rhinoconjunctivitis, Children, Adolescents, Birch
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 952 participants (actual)
- Lead sponsor
- ALK-Abelló A/SIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 7 Apr 2021 (actual)
- Primary completion
- 31 Jul 2023 (actual)
- Study completion
- 31 Jul 2023 (actual)
- First posted
- 7 May 2021 (actual)
- Results
- Posted 22 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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?.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo SLIT-tabletGelatine (fish source), mannitol and sodium hydroxide |
| Intervention/treatment | Experimental | Drug: Tree SLIT-tabletSublingual allergy immunotherapy tablet, for daily administration SQ tree SLIT-tablet |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tree SLIT-tabletSublingual allergy immunotherapy tablets | Drug | Intervention/treatment |
| Placebo SLIT-tabletPlacebo | Drug | Placebo |
Primary outcome
Average Total Combined Score (TCS) During the Birch Pollen Season (BPS)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
The primary endpoint of the trial was the average allergic rhinitis and/or conjunctivitis TCS during the BPS. The average TCS evaluates the treatment effect based on reduction in daily rhinoconjunctivitis symptoms and medication use (on a scale of 0-38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
32 secondary outcomes
Average Total Combined Score (TCS) During the Tree Pollen Season (TPS)
Time frame: During the TPS (mean duration of approximately 11 weeks)
Average Daily Symptoms Score (DSS) During the Birch Pollen Season (BPS)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Average Daily Symptoms Score (DSS) During the Tree Pollen Season (TPS)
Time frame: During the TPS (mean duration of approximately 11 weeks).
Average Daily Medication Score (DMS) During the Birch Pollen Season (BPS)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Average Daily Medication Score (DMS) During the Tree Pollen Season (TPS)
Time frame: During the TPS (mean duration of approximately 11 weeks)
Average Total Combined Score (TCS) During the Alder Hazel Pollen Season (AHPS)
Time frame: During the AHPS (mean duration of approximately 6-7 weeks)
Average Daily Symptoms Score (DSS) During the Alder Hazel Pollen Season (AHPS)
Time frame: During the AHPS (mean duration of approximately 6-7 weeks)
Average Daily Medication Score (DMS) During the Alder Hazel Pollen Season (AHPS)
Time frame: During the AHPS (mean duration of approximately 6-7 weeks)
Average Total Combined Score (TCS) During the Oak Pollen Season (OPS)
Time frame: During the OPS (mean duration of approximately 3 weeks)
Average Daily Symptoms Score (DSS) During the Oak Pollen Season (OPS)
Time frame: During the OPS (mean duration of approximately 3 weeks)
Average Daily Medication Score (DMS) During the Oak Pollen Season (OPS)
Time frame: During the OPS (mean duration of approximately 3 weeks)
Number of Severe Days During the Birch Pollen Season (BPS)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Number of Severe Days During the Tree Pollen Season (TPS)
Time frame: During the TPS (mean duration of approximately 11 weeks)
Number of Well Days During the Birch Pollen Season (BPS)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Number of Well Days During the Tree Pollen Season (TPS)
Time frame: During the TPS (mean duration of approximately 11 weeks)
Number of Symptom-free Days During the Birch Pollen Season (BPS)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Number of Symptom-free Days During the Tree Pollen Season (TPS)
Time frame: During the TPS (mean duration of approximately 11 weeks)
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS)
Time frame: During the TPS (mean duration of approximately 11 weeks)
Average Total Combined Score (TCS) (EAACI Scoring) During Birch Pollen Season (BPS)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Average Total Combined Score (TCS) (EAACI Scoring) During Tree Pollen Season (TPS)
Time frame: During the TPS (mean duration of approximately 11 weeks).
Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Birch Pollen Season (BPS) (12-17 Years Only)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Tree Pollen Season (TPS) (12-17 Years Only)
Time frame: During the TPS (mean duration of approximately 11 weeks)
Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score During the Birch Pollen Season (BPS) (5-11 Years Only)
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Treatment Satisfaction (TSQM-9)
Time frame: After ending treatment (after approximately 52 weeks of treatment)
Patient-rated Global Evaluation of Treatment Efficacy
Time frame: End of treatment (after approximately 52 weeks of treatment)
Change From Baseline in Birch Specific IgE
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Birch Specific IgG4
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF)
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Alder, Hazel and Oak Specific IgE
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Alder, Hazel and Oak Specific IgG4
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF)
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks treatment, on average)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42432760Gagnon R, Dalgaard T, Ortving GS, Gappa M, Nolte H. Efficacy and safety of the tree sublingual immunotherapy tablet in the subpopulation of Canadian children with allergic rhinitis and/or conjunctivitis: phase III trial results. Allergy Asthma Clin Immunol. 2026 Jul 11. doi: 10.1186/s13223-026-01054-w. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Monika Gappa, Prof. MD principal investigator
Evangelisches Krankenhaus Düsseldorf
80 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tree SLIT-tablet in people with Allergy, run by ALK-Abelló A/S at 80 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 80 sites in Poland, Germany, Lithuania, Slovakia, Hungary and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Total Combined Score (TCS) During the Birch Pollen Season (BPS) (time frame: During the BPS (mean duration of approximately 3-4 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04878354, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025.