Specific immunotherapy for subcutaneous application: Dose finding study to evaluate the correct dose. 4 concentrations of a birch pollen allergen extract are applied in this study. Duration of therapy 20 weeks. Primary criterion is the Conjunctival Provocation Test (CPT), i.e. comparison between treatment arms of increased amount of quantities of allergen to provoke a positive CPT at the end of treatment.
This is a dose finding study and no therapeutic study. Patients will receive in 4-weekly intervals 5x injections of 0,5 ml of a solution of modified birch pollen extract outside the pollen season. The primary endpoint therefore is not the therapeutic effect of the specific immunotherapy (effect on symptoms of allergy during the birch pollen season) but the effect on the CPT. Acc. to the EMEA "Guideline on clinical development of products for specific immunotherapy for the treatment of allergic diseases" provocation tests are accepted as primary outcomes for dose-finding studies. For the CPT increasing doses of birch pollen solutions are applied to the eye and characteristic symptoms (eye redness, weeping, itching or burning and nose dripping/blockage) are assessed: 0 = absent, 1=mild, 2=moderate, 3=severe). At a score value of \>= 5/concentration the test is considered positive and finished. It is expected that at the end of the study higher doses are necessary to provoke a positive CPT. Furthermore comparative evaluation of the safety data (AEs) in the different dosage groups is a very important parameter for the evaluation of the outcome of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
344
Subcutaneous injections Build-up = 1 day: 0,1mL + 0,2mL + 0,2mL s.c. in intervals on 30 minutes; Maintenance = 5 x single injection of 0,5 mL s.c. every 4 weeks
Conjunctival Provocation Test
Comparison between dosage groups of percentage of patients who need an increased amount of allergen to provoke a positive CPT at the end of the treatment (comparison of slope of efficacy) It is expected that at the end of the study higher doses are necessary to provoke a positive CPT. Acc. to the EMEA "Guideline on clinical development of products for specific immunotherapy for the treatment of allergic diseases" provocation tests are accepted as primary outcomes for dose-finding studies.
Time frame: At screening and after approx 22 weeks (EoS)
Laboratory parameters (immunology)
specific IgE (Birch), specific IgG1 and IgG4 (Birch). Comparison pre-post will be evaluated
Time frame: At screening and after approx. 22 weeks (EoS)
Conjunctival Provocation Test
Analysis of individual results for allergen amount
Time frame: after approx. 22 weeks
Laboratory (hematological, clinical chemistry, immunological) as a measure of safety
Clinically relevant changes need to be documented as AE. Comparison pre-post will be displayed descriptively.
Time frame: At screening and after approx. 22 weeks (EoS)
Overall assessment of safety (tolerability)at the end of the study
At the end of the study investigator and patient will give their general overall impression on the safety of the study treatment on the following scale: excellent (no side effects at all), good (some minor local side effects), moderate (major local side effects or mild systemic side effects) or unaccaptable (anaphylactic reaction). Results will be compared between dosage groups
Time frame: after approx. 22 weeks (EoS)
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Dermatology Weber
Augsburg, Germany
Licca Klinik Dermatologie
Augsburg, Germany
Allergie-Centrum-Charité
Berlin, Germany
Klinische Froschung Berlin Mitte
Berlin, Germany
Hippke, Ear-Nose-Throat Specialist and Allergy
Berlin, Germany
Universität Bonn, Klinik und Poliklinik für Dermatologie
Bonn, Germany
Klinikum Carl-Gustav Carus, Klinik+Poliklinik für HNO
Dresden, Germany
Thieme, Ear-Nose-Throat Specialist and Allergology
Duisburg, Germany
Dominicus Hautzentrum
Dülmen, Germany
Spaeth, Ear-Nose-Throat Specialist and Allergy
Düren, Germany
...and 29 more locations
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
AEs are recorded at the study visits (patients are questioned and the patient diary - where allergy specific symptoms should be recorded by the patients during 48 hrs after each injection of IMP - is assessed by the investigator and AEs recorded in the CRF if applicable) and at any time of the study when site becomes aware of an AE/SAE. AE/SAE rate is compared between the treatment groups (safety profile). Also rates of local and systemic reactions will be calculated
Time frame: at 4-weekly intervals (retrospectively at study visits)
Vital signs: Blood pressure and Heart rate as a measure of safety
Vital signs are measured a screening and every study visit. Clinically abnormal values must be assessed by the investigator and - if applicable - documented as AE. Vital signs will be evaluated descriptively
Time frame: At screening and every study visit (4-weekly)
Patient diary: Allergy specific symptoms and concomitant medication (rescue m.) for 48 hrs after application of study medication
Symptoms: urticaria, sneezing, runny nose, cough, dizziness, asthma symptoms, swelling/pain at the injection site. Symptoms documented in the diary will be judged and assessed by the investigator and transcribed as AE into the CRF if applicable Medication: Antihistaminics (Eye drops, nose spray), Sultanol, oral corticosteroids, other Intake of medication documented by the patients has to be transcribed to the CRF (Concomitant medication section)
Time frame: 48 hrs every 4 weeks after each application of study medication
Physical examination acc to local procedures as a measure of safety
A PE has to be performed at screening and end of study visit (22 weeks). Clinically abnormal findings must be assessed by the investigator and documented as AE if applicable. Data will be evaluated descriptively
Time frame: At screening and after approx. 22 weeks (EoS)