BETULA POLLEN EXTRACT for Allergic rhinitis due to birch pollen | Allergic rhinoconjunctivitis

Inclusion criteria

• {"criterion_text":"-Patients who signed and dated the informed consent form obtained prior to any study-specific examination\n-Female or male patients between 18 and 65 years of age at the time of signing the informed consent form\n-Patients with moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to birch pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, either with well-controlled mild-to-moderate asthma defined in GINA guideline (Global Initiative for Asthma, 2024) or without asthma\n-Forced expiratory volume (FEV1) in one second > 70 % of predicted normal value (only for asthmatic patients)\n-Sensitization to Betula verrucosa pollen, verified by: positive skin prick test (wheal diameter ≥ 3 mm and negative control < 2 mm and positive (histamine) control ≥ 3 mm) and serum allergen-specific IgE to Betula verrucosa ≥ 0.7 kU/L (CAP EAST class ≥ 2) and a Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) ≥ 2 (0-3 scale) based on the most severe days during one of the two BPS preceding enrolment and positive response to nasal provocation with Betula verrucosa pollen allergen extract (at least at the third concentration step)\n-Assumed compliance and ability of the patient to understand the patient’s electronic diary and to follow the instructions of the study staff\n-Compliance and ability of the patient to complete an electronic diary for self-evaluation of the symptoms and rescue medication\n-Safety laboratory results within the normal range or considered to be not clinically significant in any other case"}

Exclusion criteria

• {"criterion_text":"-Previous immunotherapy with birch pollen allergen extracts according to the homologous group of tree pollen of the \"Birch group\" / “Fagales group”, as defined in Annex 1 in the Guideline on allergen products: production and quality issues (EMEA/CHMP/BWP/304831/2008), within the last 5 years\n-Serious systemic reactions to allergen-specific immunotherapy in the past\n-Hypersensitivity to excipients of the IMP\n-Any severe or unstable lung disease e. g. active tuberculosis, cystic fibrosis, COPD\n-Severe, or partly controlled or uncontrolled asthma according to GINA guideline (Global Initiative for Asthma, 2024)\n-Asthmatic patients with FEV1 ≤ 70 % of predicted normal value at screening\n-Chronic or severe acute diseases of nose or eyes\n-Irreversible secondary disorders of the target organs (e. g. emphysema, bronchiectasis)\n-Therapy with immunoglobulins\n-Completed or ongoing treatment with an anti-IgE-antibody (like omalizumab) and/or checkpoint-inhibitor\n-Diseases of the immune system including autoimmune and immune deficiencies (with exception to well-controlled Hashimoto thyroiditis and type-1 diabetes mellitus)\n-Patients with co-sensitizations or co-allergies to any perennial or seasonal allergen (with exception of alder, hazel and hornbeam), which interfere with the conduct of the study (e. g. with the tNPT or the CSMS recording), especially if the result in SPT for this allergen is higher than that for Betula verrucosa\n-Severe acute or chronic inflammatory or infectious diseases\n-Chronic or acute diseases of the heart, kidney or liver with severe impairment of their function\n-Malignancy within the previous 5 years\n-Active chronic urticaria\n-Active severe atopic eczema\n-Alcohol, drug, or medication abuse within the past year and/or during the study\n-Existing or intended pregnancy, lactation or inadequate contraceptive measures for woman with childbearing potential or a positive pregnancy test at screening\n-Use of non-allowed medication\n-Severe psychiatric, psychological, or neurological disorders; completed or ongoing long-term treatment with tranquilizer or psychoactive drugs (including tricyclic anti-depressants)\n-Relationship or dependence with the sponsor and/or investigator\n-Patients with co-sensitizations to any perennial or seasonal allergen overlapping during PBPP or BPS but which are not cross-reactive with Betula verrucosa and, measured at the same time, with specific IgE levels ≥ class 2 CAP/PHADIA (unless the relevance can be excluded by component resolved diagnosis)\n-Legal incapacity\n-Patients who are jurisdictional or governmentally institutionalized\n-Risk of non-compliance by the patient with the study procedures\n-Simultaneous participation in other clinical trials\n-Simultaneous specific immunotherapy with other allergens\n-Participation, meaning randomization, in a trial in the last three months before enrolment\n-Contraindications for SLIT (Pitsios et al., 2015)\n-Contraindications for SPT\n-Contraindications for NPT"}

Primary endpoints

• {"endpoint_text":"-The primary (efficacy) endpoint is defined as the absolute differences in mean CSMS (Combined Symptom and Medication Score) during Peak Birch Pollen Period (PBPP) of each active treatment group compared with placebo treatment group.","definition_or_measurement_approach":"Comparison of absolute differences in mean Combined Symptom and Medication Score (CSMS) during the Peak Birch Pollen Period (PBPP) between each active dose group and placebo."}

Secondary endpoints

• {"endpoint_text":"-Absolute and relative differences in mean CSMS during the Birch Pollen Season (BPS) between active and placebo treatment groups.\n-Absolute and relative differences in mean dSS during PBPP and BPS.\n-bsolute and relative differences in the 6 mean individual symptom scores (4 nasal and 2 ocular) during PBPP and BPS.\n-Absolute and relative differences in mean dMS during PBPP and BPS.\n-Global Rhinoconjunctivitis Discomfort with a 10.0-point Visual Analogue Scale (VAS).\n-Change in Rhinoconjunctivitis quality of life questionnaire (RQLQ) between active and placebo treatment groups comparing basal and post-treatment scoring.\n-Well and severe days: A well day is defined as a day without administration of any rescue medication (dMS = 0) and with dSS < 0.34 (range 0-3). A severe day is defined (acc. to Pfaar et al., 2014) as a day with a single score = 3 in any of the six symptoms. Percentages of well and severe days will be calculated for each subject as the number of well or severe days in the PBPP and BPS in relation to the number of days comprising both periods.\n-Symptom-free days during PBPP and PBP are defined as the days with absence of symptoms, (dSS = 0), and without administration of any rescue medication (dMS = 0), expressed as percentage of days during the PBPP and BPS.\n-tNPT titrated Nasal Provocation Test: To assess the efficacy of each dose of SLI-RX-BET compared to placebo. Defined as percentage of patients with an increased dosing step and the change in number of dosing steps needed to provoke a positive response in the titrated nasal provocation test (tNPT) post-treatment compared with pre-treatment (i. e. any improvement) in each of the four study groups.This is based on the change of the response to nasal provocation (tNPT)\n-To analyse the safety and tolerability of each dose of SLI-RX-BET compared to placebo by Treatment-Emergent Adverse Drug Reactions (TEADR) and patients affected with TEADRs in each group.","definition_or_measurement_approach":"CSMS/dSS/dMS: mean and absolute/relative differences between active and placebo during PBPP and BPS. Individual symptom scores (4 nasal, 2 ocular) compared similarly. Global discomfort measured by 10-point VAS. RQLQ change comparing baseline and post-treatment. Well/severe/symptom-free days defined as per protocol (well day: dMS=0 and dSS<0.34; severe day: single symptom score=3). tNPT: percentage of patients with increased dosing step and change in number of dosing steps post- vs pre-treatment. Safety: TEADRs and number/percentage of patients affected."}

Germany

Earliest CTIS Part Ii Submission Date

05-05-2025

Latest Decision Or Authorization Date

27-05-2025

Processing Time Days

22

Number Of Sites

3

Number Of Participants

30

Primary sponsor

Full Name

ROXALL Medizin GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"MVZ Medizinisches Labor Nord MLN GmbH","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"ICRC-Weyer GmbH","duties_or_roles":"code 10; code 6","organisation_type":"Pharmaceutical company"}