Birch Pollen-induced Allergic Rhinoconjunctivitis MedDRA version: 20.0 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853
Conditions
Sponsors
STALLERGENES
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The patient must fulfil the following inclusion criteria to be eligible for the trial: 1. Able to sign and date the informed consent/assent form prior to any trial-specific procedure. Patients may check a box on the assent form if they are unable to provide a signature. (Parents and/or authorised legal representative(s) will have to give written informed consent for minors in their custody.) 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 (TSS), based on the previous birch pollen season of at least 12 out of a maximum possible score of 18 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, at screening. Retrospective ARC TSS (TSS0-18) is rated the same way as Daily Symptom Score (DSS) (DSS0-18). 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 = 0 mm]). The Sponsor will accept to include patients who have a documented positive SPT in their medical records if this SPT was performed during the previous 6 months preceding the screening visit at the same investigational site in which they are enrolled. 7. Positive specific Immunoglobulin E (IgE) to pollen allergens of Betula pendula and Bet v 1 at screening (CAP-RAST birch pollen allergens and Bet v 1 specific IgEs = 0.7 kU/L). 8. Negative urine pregnancy test on all female patients of childbearing potential or who have had their first menarche prior to randomisation. Lifestyle Considerations 9. Internet access at home or via a portable device so that patients or the parent/authorised legal representative can complete the e-Diary in a dedicated application on a mobile phone daily via internet. Patients will start scoring at randomisation, i.e., 4 months before the pollen season. Are the trial subjects under 18? yes Number of subjects for this age range: 699 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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 controller medication*. The following wash-out periods apply for as-needed asthma reliever medication at least a 6-hour wash-out of Short-Acting Beta Agonists (SABAs), a 12 hour wash-out of Long-Acting Beta Agonists (LABAs) 24h wash-out for ultra-LABAs and 5 days or 5 half-lives for Inhaled Corticosteroids. *In order to ensure that the asthmatic patients with a mild to moderate asthma status is controlled by treatment steps 1, 2 or 3 in accordance with the Global Initiative for Asthma (GINA 2022), the proper continuous asthma treatment i.e., "controller" is maintained. Only the asthma "reliever" medications must be stopped before performing spirometry. If an asthma medication is used as both 'controller' and 'reliever', such as inhaled corticosteroids (in combination with formoterol (LABA)), it must not be stopped before performing spirometry. 3. Severe or uncontrolled asthma or asthma treated 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. Eligible asthmatic patients will be those with mild and moderate asthma controlled by treatment(s) consistent GINA 2022 treatment with Steps 1, 2 or 3. 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. A documented clinically relevant history of seasonal ARC symptoms caused by an allergen source, other than tree pollen from the birch homologous group, with a season overlapping the BPS. 11. A documented clinically relevant history of perennial ARC symptoms caused by an allergen source such as animal dander to which the patient is exposed during the BPS. 12. 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 13. Ongoing treatment with prohibited treatment as listed in Section 8.2.3 or any allergen immunotherapy product including Specific Immunotherapy (SIT) or past full courses of SIT against birch pollen terminated for less than
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 awareness, easily tolerated; - 2 = Moderate symptoms, i.e., definite aw | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints will be hierarchical endpoints: • The average CSMS (CSMS0-6) over the entire BPS2. • The average ARC DSS (DSS0-18) over the entire BPS2. • The average ARC DMS (DMS0-20) over the entire BPS2 • The rhinoconjunctivitis-associated functional problems as measured with the RQLQ(S) average overall score for adolescents aged between 12 to 17 years over the entire BPS2. The rhinoconjunctivitis-associated functional problems as measured with the PRQLQ average overall score for children between 6 to 11 years over the entire BPS2. Other secondary The average ARC TCS0-38 over the worst birch pollen period during BPS1 and during BPS2. • The average ARC CSMS0-6 over the worst birch pollen period during BPS1 and during BPS2. • The average ARC TCS0-38 over BPS1. • The average ARC CSMS0-6 over BPS1. • The PSCD 2-0 (PSCD2-0) over BPS1 and over BPS2. • Patients reaching 25%, 50% and 75% of PSCD2-0 over BPS1 and over BPS2. The PNCD (PNCD2-0) over BPS1 and over BPS2. • The average ARC symptom score for each of the 6 individual symptoms (runny nose, blocked nose, sneezing, itchy nose, itchy eyes, watery eyes) over BPS1 and over BPS2. • The average ARC DSS0-18 over BPS1. • The average ARC DMS0-20 over BPS1. • The average DSS0-3 over BPS1 and BPS2. • The average DMS0-3 over BPS1 and BPS2. • The average VAS score (range 0-100) of the intensity of rhinoconjunctivitis symptoms over BPS1 and over BPS2. • Patients with rescue medication intake over BPS1 and over BPS2. The proportion of days with rescue medication intake over BPS1 and over BPS2. • Patients with a shift in the ARIA classification from baseline to BPS1 and/or to BPS2. • Patients with asthma (yes/no) over BPS1 and BPS2. • Severity of asthma as per classification by the GINA over BPS1 and BPS2. • ACQ total score over BPS1 and BPS2 in children aged 6-17 years. • ACQ score per dimension over BPS1 and BPS2 in children aged 6-17 years. • Patients with OAS (yes | — |
Countries
Austria, Bulgaria, Finland, France, Germany, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Sweden
Contacts
Public ContactDanuta Kozak
Syneos Health
Outcome results
None listed