Efficacy and Safety Study of a Sublingual Immunotherapy Solution to Treat Patients Suffering From Birch Pollen Allergic Rhinoconjunctivitis

Study Overview
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Brief Summary
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The purpose of this 2-year study is to assess the sustained clinical efficacy and safety of 300 IR/day of a sublingual solution of birch pollen allergen extract starting 4 months prior to the birch pollen season and continuing over the birch pollen season compared with placebo for reduction of rhinoconjunctivitis-related symptoms and anti-allergy medication usage.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Multi-national, Phase IIIb Study to Assess the Sustained Clinical Effect and Safety of Sublingual Immunotherapy Administered as Birch Pollen Extract Solution at a Dose of 300 IR Once Daily to Patients Suffering From Birch Pollen-induced Rhinoconjunctivitis

Conditions
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Hypersensitivity, Allergic Rhinitis, Allergic Conjunctivitis, Seasonal Allergy

Intervention / Treatment
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* Biological: Placebo
* Biological: Birch pollen allergen extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic birch pollen-related allergic rhinoconjunctivitis for at least the previous 2 pollen seasons requiring intake of symptomatic treatment. Sensitization to birch pollen demonstrated by a positive Skin Prick Test to birch pollen with wheal diameter > 3 mm and birch pollen allergens specific IgE levels ≥ 0.70 kU/L. RRTSS based on the previous or on the penultimate birch pollen season ≥ 12 out of a maximum possible score of 18. Patients with an FEV1 (Forced Expiratory Volume at one second) ≥ 80% of the predicted value. Patients who are willing to comply with the protocol. Patients having given a signed informed consent before completing any study related procedure. Exclusion Criteria: Patients with symptoms of rhinitis/rhinoconjunctivitis during the birch pollen season due to any other allergens (except alder and hazel). This includes patients with symptomatic allergic rhinitis/rhinoconjunctivitis due to cat or dog allergens, and living with these animals at home or at risk of frequent contacts with these animals (family, friends etc.) during the course of the study. Patient who previously received desensitization treatment to birch pollen and/or another Betulaceae sp. (for example hazel or alder) within the previous 5 years. Patients with ongoing treatment by immunotherapy with another allergen. Pregnancy (positive pregnancy test), breast-feeding. Female patients of childbearing potential planning a pregnancy during this study or not using a medically accepted contraceptive method (hormonal birth control [orally, injectable or by implant, for at least 2 months before enrolment], intrauterine device, spermicide used with a male condom, bilateral tubal ligation, diaphragm with spermicide, female condom, monogamous relationship with a vasectomised partner). Patients planning to move during the study or planning to leave the area during the birch pollen season for more than 1 week (7 consecutive days). Patients with moderate or severe persistent asthma (GINA 3 or 4). Patients with seasonal mild persistent asthma (GINA 2) necessitating treatment with inhaled glucocorticosteroids at a dose level greater than 400 mcg budesonide dose-equivalents. Patients with any nasal or oral condition that could interfere with the efficacy or safety assessments (such as nasal polyposis or oral inflammation). Patients with severe immune deficiency. Patients with a past or current disease, which as judged by the Investigator, may affect the patient's participation in or outcome of this study. Any other disease or condition which would place a patient at undue risk by being included in the study (according to the Investigator's opinion). Usual contra-indications of immunotherapy such as concomitant beta-blocker therapy whatever the route and/or immunosuppressive drugs. Patients treated with inhaled/systemic steroids (whatever the indication) within 4 weeks prior to Visit 1 (Screening), or with long acting systemic corticosteroids 12 weeks before Visit 1 (Screening). Patients under continuous corticotherapy (inhaled or systemic drugs). Patients following a strict low sodium diet as the study treatment contains 590 mg of sodium chloride per vial in a 10 mL solution. Investigators, co-Investigators, as well as their children or spouses and all study collaborators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo sublingual solution | Biological: Placebo<br>* 10 actuations of placebo sublingual solution once daily 5 months a year and during 2 years<br>|
| Experimental: Birch pollen allergen extract<br>Sublingual Solution of Birch pollen allergen extract 300IR once daily 5 months per year and during 2 years | Biological: Birch pollen allergen extract<br>* Sublingual solution of Birch pollen allergen extract 300IR (10 actuations) once daily 5 months per year and during 2 years<br>* Other names: Staloral Birch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Adjusted Symptom Score | Symptom score adjusted on patient's rescue medication usage | Year 2 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Rhinoconjunctivitis Total Symptom Score |  | Year 2 of treatment | 
| Average Rescue Medication Score |  | Year 2 of treatment | 
| Each of Six Individual Average Rhinoconjunctivitis Symptom Scores |  | Year 2 of treatment | 
| Average Combined Score |  | Year 2 of treatment | 
| Average Rhinoconjunctivitis Visual Analogue Scale Score |  | Year 2 of treatment | 
| Average Adjusted Visual Analogue Scale Score |  | Year 2 of treatment | 
| Rescue Medication Usage |  | Year 2 of treatment | 
| Proportion of Symptom-controlled Days |  | Year 2 of treatment | 
| Rhinoconjunctivitis Quality of Life Questionnaire |  | Year 2 of treatment | 
| Global evaluation of the efficacy by the patient |  | Year 2 of treatment | 
| Sensitization profile | sensitization profile (mono- vs poly-sensitized) is derived from the skin prick test results | Before and after each treatment period (over 2 years) | 
| Asthma |  | Before, during and after each pollen season (over 2 years) | 
| Immunological markers specific for birch pollen |  | Before and after each treatment period (over 2 years) | 
| Economical Evaluation | Proportion of days-off due to birch pollen-induced symptoms | Year 2 of treatment | 
| Wheal diameter of the birch allergen Skin prick test |  | Before and after each treatment period (over 2 years) | 
| Oral Provocation Test | Analysis on a subset of patients presenting an Oral Allergy Syndrome at study entry | Year 2 of treatment | 
| Mucosa Local Inflammation | Analysis on a subset of patients | Year 1 of treatment | 
| Safety assessments | adverse events, physical examination including vital signs and laboratory data described by number of patients in each treatment group |  20 months | 
| Average adjusted Symptom score analysis by tertiles |  | Year 2 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sublingual immunotherapy, Birch pollen extract solution, Allergic rhinoconjunctivitis