Seasonal allergic rhinitis and/or rhinoconjunctivitis with or without intermittent asthma due to birch pollen allergy MedDRA version: 20.0 Level: LLT Classification code 10066093 Term: Birch pollen allergy System Organ Class: 100000004870
Conditions
Interventions
Product Name: Depigoid Birch 5.000 DPP/ml
Product Code: Depigoid Birch 5000
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Not Applicable
CAS Number: N. A.
Current Sponsor code: De
Sponsors
LETI Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be eligible for inclusion into the study only if all of the following criteria are met: 1. Availability of an appropriately signed and dated informed consent before any study-specific examination, 2. Aged 12 to 70 years at the screening visit (V0-SCR), 3. Clinical history of at least 2 years of seasonal allergic rhinitis and/or rhinoconjunctivitis with or without intermittent asthma due to birch pollen allergy that has required repeated use of symptomatic treatment, 4. Patients must have a minimum level of perception of symptoms from previous seasons defined as at least a moderate symptom level (i.e. a score of 2 on the 4-point Likert scale) in at least 2 symptom categories prior to randomization, 5. Lung function = 80% of the predicted normal value, 6. IgE-mediated sensitization has to be verified by: • suggestive medical history, and • specific IgE reactivity to birch pollen (CAP-RAST = 2), and • a positive SPT to birch pollen at screening or within 1 month of the screening visit. An SPT is considered positive if it results in a wheal diameter of at least 3.0 mm 7. Internet access so that patients can complete the eDiary daily via internet during all 5 pollen seasons covered by the study protocol. Special criteria for patients with co-allergies: For all patients with co-allergies as a result of sensitization against grass and/or weed pollen and/or perennial allergens (e.g. house dust mites, animal dander), all of the following inclusion criteria must be fulfilled: 8. Patients do not suffer from typical symptoms against co-allergens, 9. Specific CAP-RAST result to co-allergens less than the CAP-RAST result to birch pollen. The difference has to be = 2. Alternatively, a curently performed (up to 1 month prior to screening visit) negative CPT or NPT is acceptable and outweighs a high CAP-RAST test results against the respective co-allergen. Patients with co-allergens against animal dander may be randomized even if the CAP-RAST difference is =65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1. History of significant clinical manifestations of allergy as a result of sensitization against co-allergies, particularly—but not limited to—grass or weed pollen and perennial allergens (e.g. house dust mites, cat or dog). 2. History of anaphylactic reaction 3. Moderate or severe persistent asthma (GINA 3 or 4). 4. Mild persistent asthma (GINA 2), according to the Global Initiative for Asthma Guidelines, necessitating treatment with inhaled glucocorticoids at a daily dose level of > 400 µg budesonide dose equivalents. 5. Lung function 40 in the past or at screening. 11. Any severe, uncontrolled disease or diseases that could increase the risk for patients participating in the study, which include but are not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or hematological disorders. 12. Active malignant disease during the 5 years prior to study enrollment. 13. Any significant abnormal laboratory parameter or alteration in vital signs that could increase the risk for the study patient. 14. Abuse of alcohol, drugs, or medication within 1 year prior to study enrollment. 15. Severe psychiatric, psychological, or neurological disorders. 16. Ongoing or past full courses of specific immunotherapy (SIT) against birch pollen within the last 5 years. 17. Topical and systemic treatment with ß-blockers. 18. Concomitant treatment with substances interfering with the immune system beginning 1 week prior to Visit 1-1. 19. Specific immunotherapy courses against other allergens (must be terminated at least 6 months prior to start of treatment). 20. Use of tranquillizers or psychoactive drugs that have an effect on (nor-)adrenaline within 1 week prior to Visit 1-1. 21. Use of systemic corticosteroids within 3 months prior to Visit 1-1. 22. Immunization with vaccines within 7 days prior to Visit 1-1. 23. Treatment with antihistamines for any reason other than allergic symptoms due to birch pollen allergy. 24. Patients with hypersensitivity to excipients of the IMP. 25. Changed residence between geographical regions since the last birch pollen season or not staying in the geographical region during the pre-determined birch pollen season. 26. Patients expected to be non-compliant and/or uncooperative. 27. Exposure to any investigational drug within one month or 6 half lives of the drug (whichever is longer). 28. Patients who have already participated in this study. 29. Patients who are employees of the study site, first-degree relatives, or partners of the investigator(s). 30. Any donation of germ cells, blood, organs, or bone marrow during the course of the study. 31. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. 32. Nursing (lactating) women or women with a positive pregnancy test at the screenin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is the proof of efficacy (superiority versus placebo) by means of the combined Symptom and Medication score (SMS) on nasal and ocular symptoms and their respective Rescue Medication score (RMS) for the perennial treatment regimen of Depigoid Birch 5000 DPP/mL versus placebo after 2 years (yrs) of treatment and after 5 years comprising 3 years of treatment plus 2 years treatment-free follow-up.;Secondary Objective: Difference in SMS+RMS in eDiary only for 3rd year data Differences in Symptoms score (SS),RMS,SMS during 1.,3.,4. pollen season (futility&Interim analysis(FA, IA). Changed after 2nd-year IA; 3rd-year FA will not be performed Difference in SMS incl. pulmonary symptoms Differences in SMS,SS,RMS concern. asthmatic&non-asthm. pts. Difference in the RQLQ/AdolRQLQ scores Difference in nos. of well days & hell days Differences in immunol. param. within pts/between treatm. groups Disease-modifying effect after 5 yrs Responder-analysis after 2&5 yrs Differences in laboratory param. (hemat./clinical chem.) Differences in AEs through. whole study duration incl. differences between treatm. groups in severity levels of SRs, immediate and local reactions,incl.calc. of ratios per injection Differences in vital signs, physical exam., global evaluation Differences between sympt. in the pat. diaries Differencies between sympt. reported in the pat. diaries Exam. of pharmacokinet. of AI(OH)3;Primary end point(s): The primary analysis variable is the mean integrated combined Symptom and Rescue Medication score (SMS) standardized to the total duration of the yearly pollen exposition time. It will be calculated separately for each year (resp. pollen season) after start of treatment. The SMS represents the sum of the mean daily Symptom score (SS) of rhinitis/ rhinoconjunctivitis/asthma symptoms plus the mean daily Rescue Medication score (RMS). The following 6 symptoms for allergic rhinoconjunctivitis will be scored: nasal itc | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Symptom score (SS) • Rescue medication score (MS) • Combined symptom and rescue medication score (SMS) including pulmonary symptoms: breathlessness, wheezing, cough, tightness in chest captured according to the same scoring system like the nasal/ocular symptoms. • Rhinitis QoL scores (AdolRQLQ + RQLQ) • IgE, IgG1 and IgG4 levels • Number of well days and hell days • Subjects (%) suffering from different severity levels of systemic reactions • Subjects (%) suffering from immediate local reactions (= 5 cm in diameter) • Subjects (%) suffering from delayed local reactions (= 10 cm in diameter) • Ratio of systemic reactions per injection • Ratio of local reactions per injection • Pharmacokinetics of Aluminiumhydroxid (subgroup of 24 patents only): Aluminium concentrations in plasma and urine • Investigators and patients global evaluation • Disease modifying effect (% of patients who develop asthma or allergic symptoms against allergens other than birch pollen) • Number of responders • Adverse Events ;Timepoint(s) of evaluation of this end point: Symptoms and rescue medication score, well days, hell days: : during birch pollen seasons (country-spec. approx. 2-3 months between Feb.-Jun) in the years pertaining to both the treatment and follow-up periods (years 1 to 5). Rhinitis QoL: once per birch pollen season (mid-season) IgE, IgG1 and IgG4 levels: at baseline and at the visit after the expected end of the birch pollen seasons during the treatment and follow-up periods. Pharmacokinetics of Aluminiumhydroxid: before immunotherapy, after the 1st maintenance dose and after 1 year of treatment Investigators and patients global evaluation: after 5 years Disease modifying effect: after 5 years Number of responders : once per birch pollen season Adverse events, systemic reactions, local reaction: throughout the study | — |
Countries
Czech Republic, Finland, Germany, Latvia, Lithuania, Poland, Russian Federation
Contacts
Public ContactMedical Department
LETI Pharma GmbH
Outcome results
None listed