A Dose-response Evaluation of the SQ Tree SLIT-tablet Using an Environmental Exposure Chamber

Study Overview
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Brief Summary
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The trial is a phase II, randomised, parallel-group, double-blind, placebo-controlled multi-site trial conducted in Canada. Before the start of treatment, the subjects will undergo baseline birch and oak Environmental Exposure Chamber sessions. The treatment duration is 24 weeks. The subjects will undergo birch Environmental Exposure Chamber sessions after 8, 16 and 24 weeks of treatment and an oak Environmental Exposure Chamber session after 24 weeks of treatment.

Official Title
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A Dose-response Evaluation of the SQ Tree SLIT-tablet in Subjects With Moderate to Severe Allergic Rhinoconjunctivitis Induced by Pollens From the Birch Group During Controlled Exposure in an Environmental Exposure Chamber

Conditions
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Allergic Rhinoconjunctivitis

Intervention / Treatment
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* Drug: SQ tree SLIT-tablet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained before any trial related procedures are performed Male or female aged 18 to 65 years Female subjects of child-bearing potential must have a negative urine pregnancy test and be willing to practise contraceptive methods History of moderate-to-severe rhinoconjunctivitis induced by pollens from the birch group with or without asthma despite having received treatment with symptom relieving medication during the previous 2 tree pollen seasons Positive SPT response (wheal diameter ≥ 3 mm) to Betula verrucosa Positive specific IgE against Bet v1 (≥ IgE Class 2; ≥0.70 kU/L) Willing and able to comply with the trial protocol Minimum level of rhinoconjunctivitis symptoms, defined as a TSS of at least 7 (of 18), at one timepoint during birch baseline EEC session. Exclusion Criteria: Symptoms induced by interfering allergens that are expected to be present during the periods where the subject attends the EEC sessions Rhinoconjunctivitis caused by animal hair and dander to which the subject is regularly exposed. Allergic symptoms induced by perennial allergens such as house dust mites, and moulds A clinical history of uncontrolled asthma within 3 months prior to screening Reduced lung function FEV1 (< 70% of predicted value after adequate pharmacological treatment) Asthma requiring treatment with inhaled corticosteroid within the past 3 months prior to screening Previous treatment with any allergy immunotherapy product with tree pollen allergens or a cross-reacting allergen within the past 5 years Ongoing treatment with any allergy immunotherapy product Immunosuppressive treatment within 3 months prior to the screening visit Treatment with tricyclic antidepressants, catecholamine-O-methyltransferase inhibitors, mono amine oxidase inhibitors and beta-blockers Treatment with antidepressant medication with antihistaminic effect Treatment with antipsychotic medications with antihistaminic effect Treatment with anti-IgE drugs within 130 days/5 half-lives of the drug (which ever longest) Treatment with an investigational drug within 30 days/5 half-lives of the drug (which ever longest) prior to screening Severe oral inflammation or oral wounds at randomisation Symptoms of or treatment for upper respiratory tract infection, acute sinusitis, acute otitis media or other relevant infections that have not resolved 1-week prior to the baseline birch and oak Environmental Exposure Chamber sessions and at the randomisation visit Clinically relevant nasal polyps A history of paranasal sinus surgery A history of surgery of nasal turbinates A history of anaphylaxis with cardiorespiratory symptoms A history of recurrent (defined as two or more episodes) generalised urticaria during the last 2 years A history of drug-induced (incl. Allergy Immunotherapy) facial angioedema or a family (parents and siblings) history of hereditary angioedema Any clinically relevant chronic disease (≥3 months duration) that in the opinion of the investigator would interfere with the trial assessments or the safety of the subject An uncontrolled systemic disease affecting the immune system (e.g. insulin-dependent diabetes, autoimmune disease, immune complex disease, or immune deficiency disease whether acquired or not) A history of allergy, hypersensitivity or intolerance to the investigational medicinal product (except Betula verrucosa) or any of the symptomatic medications provided in this trial Being immediate family of the investigator or trial staff, defined as the investigator's/staff's spouse, parent, child, grandparent or grandchild.

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 |
| --- | --- |
| Experimental: 12 DU SQ tree SLIT-tablet<br>Betula verrucosa, allergen extract, Oral lyophilisate | Drug: SQ tree SLIT-tablet<br> <br> |
| Experimental: 7 DU SQ tree SLIT-tablet<br>Betula verrucosa, allergen extract, Oral lyophilisate | Drug: SQ tree SLIT-tablet<br> <br> |
| Experimental: 2 DU SQ tree SLIT-tablet<br>Betula verrucosa, allergen extract, Oral lyophilisate | Drug: SQ tree SLIT-tablet<br> <br> |
| Placebo Comparator: Placebo<br>No active ingredient, Oral lyophilisate | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average total rhinoconjunctivitis symptom score | The total rhinoconjunctivitis symptom score will measured during a birch pollen challenge in the Inflamax Environmental Exposure Chamber | After 24 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average total rhinoconjunctivitis symptom score | The total rhinoconjunctivitis symptom score will measured during a birch pollen challenge in the Inflamax Environmental Exposure Chamber | After 8 and 16 weeks of treatment | 
| Average total rhinoconjunctivitis symptom score | The total rhinoconjunctivitis symptom score will measured during an oak pollen challenge in the Inflamax Environmental Exposure Chamber | After 24 weeks of treatment | 
| Adverse events | Adverse events will be grouped by number of treatment-emergent AEs and IMP-related AEs and will further summarised by treatment group and MedDRA SOC, MedDRA PT and broken down by severity, seriousness, action taken, time from first intake to AE and re-occurence after IMP administration | During the 24-weeks treatment period | 
| Vital signs |  | During the 24-weeks treatment period | 
| Lung function measures | Forced expiratory volume in 1 second and peak flow measurements will be performed. | During the 24-weeks treatment period | 
| Changes in significant clinical safety laboratory values | Standard haematology, biochemistry, urinalysis analysis will be performed for each subject before and after the 24-weeks treatment period. | Before and after the 24-weeks treatment period |