Birch Pollen-induced Allergic Rhinoconjunctivitis MedDRA version: 20.0 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853
Conditions
Interventions
Trade Name: STALORAL BIRCH
Pharmaceutical Form: Sublingual spray, solution
INN or Proposed INN: Birch pollen allergen extract
Other descriptive name: BETULA
Concentration unit: BAU/ml Bioequivalent Al
Sponsors
STALLERGENES
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to sign and date the informed consent/assent prior to any trial-specific procedure. (Parents and/or authorised legal representatives will have to give written informed consent for minors in their custody. Children and adolescents will be asked to sign an assent form, dependent on country-specific requirements and Investigator assessment.) 2. Covered by a health insurance system as per local regulation. Demographics and Medical History 3. Aged =5 to =17 years old at the randomisation visit. 4. Documented, physician diagnosed, clinically relevant history of moderate to severe ARC induced by birch pollen (with or without asthma) despite having received treatment with symptom-relieving medication during at least 1 previous birch pollen season for ages 4 through 6 or at least 2 previous birch pollen seasons for ages 7 through 17 years at screening. 5. A Retrospective ARC Total Symptom Score based on the previous birch pollen season = 12 out of a maximum possible score of 18 as evaluated by the patient or by the parent/authorised legal representative AND a retrospective score of at least 30 on a general VAS (0-100) on the severity of symptoms as evaluated by the patient or by the parent/authorised legal representative if the patient is not able to perform the assessment. Screening Tests and Evaluations 6. Positive Skin Prick Test (SPT) to Betula pendula at screening visit (The SPT is considered positive if it results in a wheal diameter = 3.0 mm [with positive control (histamine) = 3.0 mm and negative control =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Medical history 1. Any clinical deterioration of asthma (i.e., asthma exacerbation) that resulted in emergency procedure/treatment or treatment with systemic corticosteroids within 3 months prior to randomisation. 2. For patients =7 years old: Reduced lung function at randomisation defined as Forced Expiratory Volume in 1 second (FEV1) < 70% of the predicted value. For patients with asthma, this is assessed on the patient’s usual asthma medication following at least a 6-hour wash-out of Short-Acting Beta Agonists (SABAs), a 12-hour wash-out of Long-Acting Beta Agonists (LABA) and 24 h wash-out for ultra-long acting LABAs. 3. Uncontrolled asthma with asthmatic therapies consistent with steps 4 or 5 as defined by Global Initiative for Asthma (GINA 2022) received within 12 months prior to entry in the trial. 4. Oral inflammations such as oral lichen planus, oral ulcerations or oral mycosis. 5. Acute or chronic inflammatory or infectious upper airway diseases (excepted mild to moderate asthma) including recurrent acute or chronic sinusitis. 6. History of eosinophilic oesophagitis. 7. 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. 8. Any disease that prohibits the use of adrenaline (e.g., hyperthyroidism). 9. Any severe, uncontrolled disease that, upon investigator judgment, could increase the risk for trial patients (including but not limited to cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, haematological disorders, diseases of the immune system including autoimmune diseases and immune deficiencies of current clinical relevance, active malignancies). Screening Tests and Evaluations 10. Immunodetection with ImmunoCAP ISAC of specific antigen(s) of allergen(s) other than birch pollen (whether seasonal or perennial allergens), associated with clinically relevant symptoms confirming that patients are allergic to this/these allergen(s) seasonal/ perennial allergen(s) based on clinical judgment and medical records, and anticipated exposure to this/these allergen(s) during the two study treatment periods. Relevant clinical symptoms of respiratory allergy are 4 nasal symptoms (runny nose, blocked nose, sneezing, itchy nose), associated or not to 2 eye related items (itchy eyes, watery eyes), associated or not to asthma (mainly cough, wheezing, shortness of breath) 11. Any significant abnormal laboratory parameter or alteration in vital signs that could increase the risk for the patient, in the opinion of the Investigator. Medication 12. Ongoing treatment with any allergy immunotherapy product including Specific Immunotherapy (SIT), or past full courses of SIT against birch pollen terminated for less than 5 years or past courses of SIT for other allergens terminated for less than 6 months prior to start of randomisation. 13. Patients requiring continuous treatment with systemic corticosteroids for any indications. 14. Patients requiring continuous treatment with ß-blockers or with Monoamine Oxidase Inhibitors (MAOIs). 15. Treatment with an immunosuppressive (ATC code L04 or L01) within 3 months prior to the screening visit. 16. Hypersensitivity to the IMP or contraindication to the use of rescue medications (i.e., antihistamine and nasal corticosteroids). 17. Patients f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: End of the study;Main Objective: To demonstrate clinical efficacy of STALORAL® Birch 300 IR on Allergic Rhino-Conjunctivitis (ARC) symptoms and rescue medication use during the second birch pollen season of the trial, in children and adolescents with birch pollen-induced ARC;Secondary Objective: Key secondary objective: To assess the effect of STALORAL® Birch 300 IR on symptoms and medications along with rhinoconjunctivitis-associated quality of life during the second birch pollen season. Other objectives: • To assess combined ARC symptoms and medications score during the worst birch pollen period, each year and over two consecutive pollen seasons. • To assess changes in the ARIA classification. • To assess individual symptoms and medication scores, asthma status and control, Oral Allergy Syndrome (OAS), quality of life of patients, patient immunological status, health-economic parameters, patient medication compliance over two consecutive pollen seasons. • To assess biomarkers in future research (e.g., IgG2, IgA). • To assess an exploratory symptom and medication score over two consecutive birch pollen seasons. • To evaluate the safety and clinical tolerability of STALORAL® Birch 300 IR in children and adolescents 5 to 17 years old with birch pollen associated ARC.;Primary end point(s): The average ARC Total Combined Score (TCS0-38) is defined as the average of the daily (non-missing) ARC TCS0-38. The daily ARC TCS0-38 is the sum of the ARC Daily Symptom Score (0-18) (DSS0-18) and the ARC Daily Medication Score (0-20) (DMS0-20) and thus ranges from 0 to 38 points: TCS0-38 = DSSS0-18 + DMS0-20. • The DSS0-18 is the sum of 6 ARC symptoms scores with 4 rhinitis related items (runny nose, blocked nose, sneezing, itchy nose) and 2 eye related items (itchy eyes, watery eyes): each symptom is rated on a 4- point scale from 0 to 3: - 0 = No symptom; - 1 = Mild symptoms, i.e., sign/symptom clearly present, but minimal awarenes | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary Efficacy variables: • The average ARC Combined Symptom Medication Score (CSMS0-6) is defined as the average of the daily (non-missing) ARC CSMS0-6 with CSMS0-6 defined as: CSMS0-6= DSS0-3 +DMS0-3 - The DSS0-3 is calculated as the average of the 6 scores for each individual ARC symptom (runny nose, blocked nose, sneezing, itchy nose, itchy eyes, watery eyes) rated on a 4- point scale from 0 to 3 (0 = None; 1 = Mild; 2 = Moderate; 3 = Severe). - The DMS0-3 is based on rescue medication intake and ranges from 0 to 3 (0=No rescue medication taken; 1=antihistamine as eye drops and/or oral form; 2=nasal corticosteroid; 3= oral corticosteroid as a concomitant treatment to manage asthma exacerbation, if the case arises). • The average DSS0-18 calculated as the average of the daily (non-missing) DSS0-18 • The average DMS0-20 calculated as the average of the daily (non-missing) DMS0-20. • The overall RQLQ(S) score and the overall PRQLQ score, calculated as the mean of responses. Other secondary Efficacy variables: • The average ARC TCS0-38 and the average CSMS0-6 will also be analysed to answer other secondary efficacy endpoints. • The Proportion of Symptom-Controlled Days (PSCD2-0) calculated as the proportion of days during the birch pollen season with no rescue medication intake (DMS0-20=0) and controlled symptoms (DSS0-18 =2). • Controlled patient (CP), i.e., patient with 25%, 50% or 75% of symptom-controlled days (CP25, CP50 and CP75 based on PSCD2-0) during the birch pollen season • The Proportion of Not-Controlled Days (PNCD) calculated as the proportion of days during the birch pollen season with one of the following: - at least one individual symptom score = 2 and DMS0-20>0, or - at least two individual symptom scores = 2 whatever the DMS0-20, or - at least one individual symptom score = 3 whatever the DMS0-20. • The 6 average individual ARC symptom scores (scale 0-3) for runny nose, blocked nose, sneezing, itchy nose, itch | — |
Countries
Austria, Bulgaria, Finland, France, Germany, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Sweden
Contacts
Public ContactAurélie ETRINGER
ICTA PM
Outcome results
None listed