SUBLIVAC FIX Birch Dose Tolerability/Dose Range Finding

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to determine the optimal effective dose of SUBLIVAC FIX Birch based on reduction of upper airways reactivity after 5 months of treatment with different dosages of SUBLIVAC FIX Birch compared to placebo. Furthermore, safety and tolerability will be assessed by the number of related Adverse Events of different dosages of SUBLIVAC FIX Birch compared to placebo.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled Study to Determine Safety, Tolerability and the Optimal Effective Dose of SUBLIVAC FIX Birch in Patients With Allergic Rhinitis/Rhinoconjunctivitis Caused by Birch Pollen

Conditions
-----------------
Allergic Rhinitis, Allergic Rhinoconjunctivitis

Intervention / Treatment
-----------------
* Drug: SUBLIVAC FIX Birch


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent Age ≥ 18 ≤ 60 years Allergic rhinitis/rhinoconjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma FEV1 > 70% for patients with a history of asthma, FEV > 70% or PEF > 80% for patients without a history of asthma A positive SPT (mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) for birch pollen assessed within 1 year before randomization. Positive serum specific anti-birch IgE-test (> 0.7 U/mL) A positive TNPT for birch pollen at screening (Lebel score ≥ 6) at 10,000 AU/mL Exclusion Criteria: Patients with (expected) clinically relevant symptoms during the course of the trial due to concomitant sensitization i.e. positive SPT (mean wheal diameter ≥ 3mm) to allergens other than birch pollen Patients sensitized to pets should not be included if they are regularly exposed to pets and are symptomatic upon exposure to pets Completed immunotherapy (SCIT or SLIT) with birch pollen allergens within the past 5 years Completed unsuccessful specific immunotherapy in the past Vaccination within one week before start of therapy or during the initiation phase Anti-IgE therapy within the 6 months prior to inclusion and during the study Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs Active malignancies or any malignant disease during the previous 5 years Severe uncontrolled diseases that could increase the risk for patients participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or haematological disorders Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study Moderate to severe nasal obstructive diseases that preclude a TNPT (septal deviation, nasal polyps, recent nasal surgery, etc.) Diseases with a contraindication for the use of Adrenaline (e.g. hyperthyroidism, glaucoma) Use of systemic steroids within 4 weeks before start of the study and during the study Treatment with systemic and local β-blockers Participation in a clinical study with a new investigational drug within the last 3 months or for a biological within the last 6 months prior to or during the study Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or -pill) Alcohol, drug or medication abuse within the past year Any clinically significant abnormal laboratory parameter at screening Lack of cooperation or compliance Severe psychiatric, psychological, or neurological disorders Patients who are employees of the institution or 1st grade relatives or partners of the investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SUBLIVAC FIX Birch 0 AUN/ml<br> | Drug: SUBLIVAC FIX Birch<br>* Comparison of different dosages to placebo<br>|
| Active Comparator: SUBLIVAC FIX Birch 3,333 AUN/ml<br> | Drug: SUBLIVAC FIX Birch<br>* Comparison of different dosages to placebo<br>|
| Active Comparator: SUBLIVAC FIX Birch 10,000 AUN/ml<br> | Drug: SUBLIVAC FIX Birch<br>* Comparison of different dosages to placebo<br>|
| Active Comparator: SUBLIVAC FIX Birch 20,000 AUN/ml<br>Evaluation of the SUBLIVAC FIX Birch 20,000 AUN/ml by an independent safety committee | Drug: SUBLIVAC FIX Birch<br>* Comparison of different dosages to placebo<br>|
| Active Comparator: SUBLIVAC FIX Birch 40,000 AUN/ml<br>Start of SUBLIVAC FIX Birch 40,000 AUN/ml arm depends on safety in the SUBLIVAC FIX Birch 20,000 AUN/ml arm evaluated by an independent safety committee | Drug: SUBLIVAC FIX Birch<br>* Comparison of different dosages to placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasal Provocation Test (NPT) |  | 5 months | 
| Number of related AEs |  | First ten days of study medication intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum specific immunoglobulin levels (IgE, IgG, IgG4) |  | 5 months | 
| Number of local and systemic reactions |  | Duration of study medication intake (approximately 5 months) | 
| Peak Nasal Inspiratory Flow (PNIF) |  | 5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sublingual immunotherapy, Dose range finding, Dose tolerability, Birch pollen, Allergic rhinitis/rhinoconjunctivitis, Safety, Immunogenicity