Moderate to severe birch pollen induced allergic rhinitis/rhinoconjunctivitis with or without mild to moderate persistent asthma. MedDRA version: 18.0 Level: LLT Classification code 10001726 Term: Allergic rhinitis due to pollen System Organ Class: 100000004870
Conditions
Interventions
Product Name: SUBLIVAC FIX Birch 40.000 AUN/ml
Product Code: SUBLIVAC FIX Birch
Pharmaceutical Form: Oromucosal drops
INN or Proposed INN: Allergen extract of Betula verrucosa
Current Sponsor code: SU
Sponsors
HAL Allergy B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent 2. Age = 18 and =65 years 3. Moderate-to-severe birch pollen induced allergic rhinitis/rhinoconjunctivitis based on ARIA classification for at least 2 consecutive years24 4. FEV1 > 70% (of predicted value) for patients with a history of asthma, FEV1 > 70% or PEF > 80% (of predicted value) for patients without a history of asthma 5. Positive SPT for birch pollen (mean wheal diameter = 3mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter = 3mm)) assessed during screening. 6. Serum specific anti-birch IgE concentration >0.7 U/ml Inclusion criteria to be assessed at Visit 2 before randomisation: 7. Patients should be willing and capable to complete an e-diary daily during the birch pollen season (= 60% compliance in completion between Visit 1 and 2). 8. A positive Nasal Provocation Test to birch pollen (per appendix 3) at Visit 2 (Lebel score = 6)25 or a documented positive test within 1 year before start of treatment Inclusion criteria for Safety-Extension period: 1 Signed updated informed consent including Safety-Extension period details 2 Patients that completed the double blind period of the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 360 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Patients sensitized and symptomatic to pets should not be included if they are regularly exposed to pets 2. Specific immunotherapy (SCIT or SLIT) with birch pollen or a cross-reacting allergen within the last 5 years 3. SPT positive (mean wheal diameter = 3mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter = 3mm)) patients to allergen(s) other than birch pollen, in the absence of a negative provocation test for this allergen(s), who are expected to have clinically relevant symptoms during the birch pollen season 4. Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the last 5 years 5. (Ongoing) allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) during the study period 6. Vaccination one week before start of treatment and/or during the up-dosing phase 7. Treatment with experimental products within the last 3 months or biologicals (including anti-IgE or TNF- a treatment) within the last 6 months or during the study 8. Uncontrolled asthma or other active respiratory diseases 9. Clinically significant chronic sinusitis, ocular infection or severe inflammation of the oral mucosa 10. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs 11. Active malignancies or any malignant disease in the last 5 years 12. Acute or chronic disease that in the opinion of the investigator is an additional risk for the patients, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, or haematological disorders 13. Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma) 14. Use of systemic corticosteroids 4 weeks before the study 15. Treatment with systemic or local ß-blockers 16. Known hypersensitivity to any of the excipients (Disodium phosphate dihydrate, Sodium dihydrogen phosphate dehydrate, Aminocaproic acid, Peppermint oil, Caramel Colorant or Glycerol) 17. A positive urine pregnancy test, lactation or inadequate contraceptive methods (adequate methods: oral contraceptives, IUD, condom use and having no sexual relationship with a man) 18. Alcohol-, drug or medication abuse 19. Lack of co-operation or compliance 20. Severe psychiatric, psychological, or neurological disorders 21. Any physical or mental condition that precludes administration or allergen-specific immunotherapy, compliance or participation in a clinical trial 22. Patients who are employees of the department, 1st grade relatives, or partners of the investigator 23. Patients who have planned holidays outside the country for more than 7 continuous days during the defined pollen season (1st of March till 31st of May)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: To assess clinical efficacy of sublingual immunotherapy with SUBLIVAC FIX Birch (40.000 AUN/ml), compared to placebo, in patients suffering from birch pollen induced rhinitis/rhinoconjunctivitis, measured by a combined rhinoconjunctivitis symptoms score and medication score during the birch pollen season.;Secondary Objective: Secondary objectives: • To assess clinical efficacy of sublingual immunotherapy with SUBLIVAC FIX Birch during the peak pollen season compared to placebo • To assess the effect of sublingual immunotherapy with SUBLIVAC FIX Birch on Quality of Life (QoL) during the pollen season compared to placebo • Changes in serum specific immunoglobulin levels after treatment with sublingual immunotherapy with SUBLIVAC FIX Birch compared to placebo • To assess the effect of sublingual immunotherapy with SUBLIVAC FIX Birch on the percentage of responders compared to placebo Safety objectives: • Safety and tolerability of sublingual immunotherapy with SUBLIVAC FIX Birch compared to placebo •Safety and tolerability of sublingual immunotherapy with SUBLIVAC FIX Birch for 6 months during the Safety-Extension period;Primary end point(s): Primary endpoint: The primary endpoint is the difference in mean Combined Symptom Medication Score (CSMS) between the active vs. placebo treatment group, assessed during birch pollen season.;Timepoint(s) of evaluation of this end point: During Birch pollen season (e-diary) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the study are: 1. Difference in mean CSMS between the active vs. placebo treatment group, assessed during the birch peak pollen season 2. Difference in daily Symptom Score (dSS) assessed during the birch (peak) pollen season between the active vs. placebo treatment group. 3. Difference in daily Medication Score (dMS) assessed during the birch (peak) pollen season in the active vs. placebo treatment group. 4. Difference between active and placebo treatment in Quality of Life (QoL) during the birch pollen season and End Of Treatment (EOT), determined by standardized (rhinoconjunctivitis) QoL questionnaire (RQLQ-S and EQ-5D) for all patients and for patients with birch pollen induced concomitant asthma by an additional asthma control questionnaire (ACQ) 5. Differences in serum specific immunoglobulin levels (IgE, IgG, IgG4) in the active vs. placebo treatment group after treatment. 6. Differences in number of 'well days' and 'severe days' between the active and placebo treatment The exploratory endpoint of the study is: 7. Difference in mean CSMS between the active and placebo treatment group using the placebo score-based period. Safety endpoints: 8. Safety assessed by local and systemic reactions, (serious) adverse events, blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG in the active treatment vs. placebo group before, during and after treatment. 9. Safety and tolerability of sublingual immunotherapy with SUBLIVAC FIX Birch for 6 months during the Safety-Extension period of the study assessed by (serious) adverse events, physical examination and vital;Timepoint(s) of evaluation of this end point: Endpoints no 1, 2, 3: birch peak pollen season Endpoint 4: during the birch pollen season and at the End Of Treatment (EOT), Endpoint 5: after treatment Endpoint 6: during the birch pollen season Endpoint 7: placebo score-based period (four weeks with the | — |
Countries
Belgium, Czech Republic, Germany, Poland, Slovakia
Contacts
Public ContactClinical Trial Management
HAL Allergy B.V.
Outcome results
None listed