A Study in Children and Adolescents With Birch Pollen-induced Rhinoconjunctivitis
- Conditions
- Allergy
- Interventions
- Drug: Placebo SLIT-tabletDrug: Tree SLIT-tablet
- Registration Number
- NCT04878354
- Lead Sponsor
- ALK-Abelló A/S
- Brief 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 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 952
-
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
- Impairment of daily activities, leisure and/or sport
- Impairment of school or work
- Troublesome symptoms
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo SLIT-tablet Gelatine (fish source), mannitol and sodium hydroxide Intervention/treatment Tree SLIT-tablet Sublingual allergy immunotherapy tablet, for daily administration SQ tree SLIT-tablet
- Primary Outcome Measures
Name Time Method Average Total Combined Score (TCS) During the Birch Pollen Season (BPS) 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.
- Secondary Outcome Measures
Name Time Method Average Total Combined Score (TCS) During the Tree Pollen Season (TPS) During the TPS (mean duration of approximately 11 weeks) 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.
Average Daily Symptoms Score (DSS) During the Birch Pollen Season (BPS) During the BPS (mean duration of approximately 3-4 weeks) 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.
Average Daily Symptoms Score (DSS) During the Tree Pollen Season (TPS) During the TPS (mean duration of approximately 11 weeks). 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.
Average Daily Medication Score (DMS) During the Birch Pollen Season (BPS) During the BPS (mean duration of approximately 3-4 weeks) 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.
Average Daily Medication Score (DMS) During the Tree Pollen Season (TPS) During the TPS (mean duration of approximately 11 weeks) 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.
Average Total Combined Score (TCS) During the Alder Hazel Pollen Season (AHPS) During the AHPS (mean duration of approximately 6-7 weeks) 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.
Average Daily Symptoms Score (DSS) During the Alder Hazel Pollen Season (AHPS) During the AHPS (mean duration of approximately 6-7 weeks) 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.
Average Daily Medication Score (DMS) During the Alder Hazel Pollen Season (AHPS) During the AHPS (mean duration of approximately 6-7 weeks) 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.
Average Total Combined Score (TCS) During the Oak Pollen Season (OPS) During the OPS (mean duration of approximately 3 weeks) 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.
Average Daily Symptoms Score (DSS) During the Oak Pollen Season (OPS) During the OPS (mean duration of approximately 3 weeks) 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.
Average Daily Medication Score (DMS) During the Oak Pollen Season (OPS) During the OPS (mean duration of approximately 3 weeks) 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.
Number of Severe Days During the Birch Pollen Season (BPS) During the BPS (mean duration of approximately 3-4 weeks) 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.Number of Severe Days During the Tree Pollen Season (TPS) During the TPS (mean duration of approximately 11 weeks) 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.Number of Well Days During the Birch Pollen Season (BPS) During the BPS (mean duration of approximately 3-4 weeks) 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.Number of Well Days During the Tree Pollen Season (TPS) During the TPS (mean duration of approximately 11 weeks) 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.Number of Symptom-free Days During the Birch Pollen Season (BPS) During the BPS (mean duration of approximately 3-4 weeks) 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.
Number of Symptom-free Days During the Tree Pollen Season (TPS) During the TPS (mean duration of approximately 11 weeks) 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.Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS) During the BPS (mean duration of approximately 3-4 weeks) 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
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS) During the TPS (mean duration of approximately 11 weeks) 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.
Average Total Combined Score (TCS) (EAACI Scoring) During Birch Pollen Season (BPS) During the BPS (mean duration of approximately 3-4 weeks) 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.
Average Total Combined Score (TCS) (EAACI Scoring) During Tree Pollen Season (TPS) During the TPS (mean duration of approximately 11 weeks). 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.
Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Birch Pollen Season (BPS) (12-17 Years Only) During the BPS (mean duration of approximately 3-4 weeks) 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.Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Tree Pollen Season (TPS) (12-17 Years Only) During the TPS (mean duration of approximately 11 weeks) 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.Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score During the Birch Pollen Season (BPS) (5-11 Years Only) During the BPS (mean duration of approximately 3-4 weeks) 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.Treatment Satisfaction (TSQM-9) After ending treatment (after approximately 52 weeks of treatment) 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.
Patient-rated Global Evaluation of Treatment Efficacy End of treatment (after approximately 52 weeks of treatment) 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.Change From Baseline in Birch Specific IgE 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) Birch specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation
Change From Baseline in Birch Specific IgG4 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) Birch specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF) 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) 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.
Change From Baseline in Alder, Hazel and Oak Specific IgE 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 in alder, hazel and oak specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Change From Baseline in Alder, Hazel and Oak Specific IgG4 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 in alder, hazel and oak specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) 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) 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.
Trial Locations
- Locations (79)
Aranyklinika Kft
🇭🇺Szeged, Csongrád, Hungary
"Inlita" JSC Santara CTC
🇱🇹Vilnius, Vilniaus Apskritis, Lithuania
Medical University of Vienna
🇦🇹Vienna, Austria
Praxis Dr. med. Karsten Jünger
🇩🇪Herxheim, Rheinland-Pfalz, Germany
Hautarztpraxis Dr. med. Daniela Kasche
🇩🇪Hamburg, Germany
Erasmus MC - Sophia Childrens Hospital
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Kinder- u. Jugendmedizin
🇩🇪Heidelberg, Baden-Württemberg, Germany
ENT Research GmbH
🇩🇪Essen, Nordrhein-Westfalen, Germany
Universitätsmedizin der JGU
🇩🇪Mainz, Rheinland-Pfalz, Germany
HNO-Praxis am Neckar
🇩🇪Heidelberg, Germany
"Seimos gydytojas" JSC
🇱🇹Vilnius, Vilniaus Apskritis, Lithuania
ALERGO-MED Spolka z o.o.
🇵🇱Tarnów, Malopolskie, Poland
KliFOs - Klinische Forschung Osnabrück
🇩🇪Osnabrück, Niedersachsen, Germany
Praxis Dr. Yury Yarin
🇩🇪Dresden, Sachsen, Germany
Universitätsklinikum Münster
🇩🇪Münster, Nordrhein-Westfalen, Germany
Svábhegy Plusz Kft
🇭🇺Budapest, Hungary
Public Enterprise State Scient
🇷🇺Moscow, Russian Federation
"All-Med" Specjalistyczna Opieka Medyczna
🇵🇱Wroclaw, Poland
Klinikum rechts der Isar der TUM
🇩🇪Munich, Bayern, Germany
Semmelweis Egyetem
🇭🇺Budapest, Hungary
NZOZ E-Vita
🇵🇱Bialystok, Podlaskie, Poland
Univerzitna Nemocnica Martin
🇸🇰Martin, Slovakia
EMED s.r.o.
🇸🇰Prešov, Slovakia
Zoll-Med s.r.o., Ambulancia klinickej imunologie a alergologie
🇸🇰Rimavska Sobota, Slovakia
Astma, Allergi- og Lungeklinik
🇩🇰Copenhagen, Denmark
Gentofte Hospital Allergy Clinic
🇩🇰Hellerup, Denmark
Alerginiu susirgimu diagnostikos ir gydymo centras
🇱🇹Vilnius, Lithuania
Centrum Medyczne ALL-MED
🇵🇱Kraków, Małopolskie, Poland
Michal Bogacki DOBROSTAN
🇵🇱Wroclaw, Poland
"Medicum centrum" JSC
🇱🇹Taurage, Tauragės Apskritis, Lithuania
Allergy clinic "Perspektyvos" JSC
🇱🇹Vilnius, Vilniaus Apskritis, Lithuania
"Center of Innovative Allergology" JSC
🇱🇹Vilnius, Lithuania
Centrum Medyczne PRATIA Bydgoszcz
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Specjalist. Praktyka Lek. dr n.med. Joanna Orlicz-Widawska
🇵🇱Katowice, Śląskie, Poland
Kispesti Egeszsegugyi Intezet
🇭🇺Budapest, Hungary
Medisch Spectrum Twente
🇳🇱Enschede, Overijssel, Netherlands
Hospital of University of Health Sciences Kauno Klinikos
🇱🇹Kaunas, Lithuania
Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna
🇵🇱Lublin, Lubelskie, Poland
Malopolskie Centrum Alergologii
🇵🇱Krakow, Małopolskie, Poland
Centrum Medyczne PROMED
🇵🇱Kraków, Małopolskie, Poland
Indywidualna Specjalistyczna Praktyka Lekarska lek. med. Elzbieta Matusz
🇵🇱Gryfice, Poland
"CD8 Klinika" JSC
🇱🇹Kaunas, Kauno Apskritis, Lithuania
Alergotest s.c. Specjalistyczne Centrum Medyczne
🇵🇱Lublin, Poland
Gabinet Lekarski Pediatryczno-Alergologiczny Zenon Bukowczan
🇵🇱Sucha Beskidzka, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Uslug Medycznych "PROXIMUM" Sp. z o.o.
🇵🇱Wroclaw, Poland
WWCOiT im. M. Kopernika w Lodzi, Osrodek Pediatryczny im. dr J.Korczaka
🇵🇱Łódź, Poland
Centrum Alergologii Prof. K. Buczyłko Spółka z o.o.
🇵🇱Łódź, Poland
ETG Skierniewice
🇵🇱Skierniewice, Łódzkie, Poland
ALERGO H2B s.r.o.
🇸🇰Komárno, Nitriansky Kraj, Slovakia
Niepubliczny Zaklad Opieki Zdrowotnej "ALERGOLOGIA", Poradnia Alergologiczna
🇵🇱Szczecin, Zachodniopomorskie, Poland
SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. N.Barlickiego
🇵🇱Łódź, Poland
NSZOZ Puls - Med Anna Bogusz, Agnieszka Musielak Sp.J.
🇵🇱Skarżysko-Kamienna, Świętokrzyskie, Poland
MedKol, s.r.o.
🇸🇰Nové Zámky, Slovakia
DANIMED, spol. s.r.o.
🇸🇰Levice, Slovakia
CHU Sainte-Justine
🇨🇦Montréal, Quebec, Canada
Allergy Center Vienna West
🇦🇹Vienna, Austria
Practice Dr Jean-Benoit Martinot
🇧🇪Erpent, Namur, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Oost-Vlandeeren, Belgium
UZ Leuven
🇧🇪Leuven, Vlaams Brabant, Belgium
Clinique specialisee en allergie de la capitale
🇨🇦Québec, Canada
Aarhus Universitetshospital, Astma, Allergi- og Lungeklinikken for Born
🇩🇰Aarhus, Denmark
Gemeinschaftspraxis für Kinder und Jugendmedizin
🇩🇪Mannheim, Baden-Württemberg, Germany
Evangelisches Krankenhaus Düsseldorf - Klinik für Kinder- und Jugendmedizin
🇩🇪Düsseldorf, Nordrhein-Westfalen, Germany
HNO Praxis Dr. Uta Thieme
🇩🇪Duisburg, Germany
Universitätsklinikum Gießen und Marburg GmbH - Klinik für Hals-, Nasen- und Ohrenheilkunde Sektion Rhinologie und Allergologie
🇩🇪Marburg, Hessen, Germany
Praxis Dr.J. Funck
🇩🇪Neuss, Nordrhein-Westfalen, Germany
Kinderarztpraxis Dr. med. Siegfried Simmet und Simon Traub
🇩🇪Schweigen-Rechtenbach, Rheinland-Pfalz, Germany
JSC Ausros Medicinos Centras
🇱🇹Kaunas, Kauno Apskritis, Lithuania
Heim Pál Gyermekkórház
🇭🇺Budapest, Hungary
Centrum Medyczne Pratia Czestochowa
🇵🇱Czestochowa, Poland
ETG Kielce
🇵🇱Kielce, Poland
Centrum Medyczne Plejady
🇵🇱Kraków, Poland
LLC "Olla-Med"
🇷🇺Moscow, Moskva, Russian Federation
NRPC Pediatric Hematology, Oncology, Immunology n.a. Dmitriya Rogacheva - Multispecialty
🇷🇺Moskva, Moscow, Russian Federation
FGBU "Scientific center of children health" of RAMS
🇷🇺Moscow, Moskva, Russian Federation
FGBUN" Federal Research Center for Nutrition and Biotechnology "
🇷🇺Moskva, Russian Federation
SIMIDA s.r.o.
🇸🇰Vráble, Slovakia
Ambulancia klinickej imunologie a alergologie
🇸🇰Šurany, Slovakia
Kinder- und Jugendärzte
🇩🇪Hürth, Nordrhein-Westfalen, Germany