PURETHAL® Mites Dose Range Finding Study in Patients With Persistent Allergic Rhinitis/Rhinoconjunctivitis

Study Overview
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Brief Summary
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The objective of the present study is to characterize the dose-response relationship of PURETHAL® Mites with a nasal provocation test in order to support the optimal dose in terms of clinical efficacy and safety. For this purpose 5 groups of 50 patients, suffering from rhinitis or rhinoconjunctivitis due to House Dust Mite Allergy will be treated during 1 year. Before start, after 6 months of treatment and at the end of the study patients will be subjected to a nasal provocation test.

Official Title
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A Multi-centre, Randomized, Double-blind, Placebo-controlled, Dose Range Finding Study to Identify the Optimal Dose of PURETHAL® Mites SCIT in Patients With House Dust Mites-induced Persistent Allergic Rhinitis/Rhinoconjunctivitis

Conditions
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Allergic Rhinitis, Allergic Rhinoconjunctivitis

Intervention / Treatment
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* Biological: Placebo
* Biological: PURETHAL Mites 6,667 AU/ml
* Biological: PURETHAL Mites 20,000 AU/ml
* Biological: PURETHAL Mites 50,000 AU/ml
* Biological: PURETHAL Mites 100,000 AU/ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Patients (male or female) must be ≥ 18 and ≤ 60 years at screening Patients with allergic rhinitis or rhinoconjunctivitis for at least 1 year; allergic symptoms related to HDM, with or without concomitant clinically stable controlled mild to moderate asthma (according to GINA classification) Patients with a history of concomitant asthma should have a FEV1 > 70% at inclusion. Patients without a history of asthma should have a FEV1 > 70% or a PEF > 80%. Positive SPT to HDM D. pter and/or D. far Serum specific IgE-test (ssIgE) level for HDM D. pter or D. far at screening Positive nasal provocation test for HDM extract at screening Exclusion Criteria: Current clinically relevant symptoms of seasonal rhinitis/rhinoconjunctivitis caused by other allergen(s) than HDM (with a demonstrated positive SPT for this allergen) at the time of inclusion Patients sensitized to animals should not be included if they are symptomatic upon exposure and regularly exposed to animals Completed allergen-specific immunotherapy (SCIT or SLIT) with HDM within the last 5 years Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the past 5 years Allergen-specific immunotherapy (SCIT or SLIT) with other allergens than HDM during the study period Any vaccination one week before start of therapy and during the up-dosing phase Any anti-IgE therapy within the last 6 months prior to inclusion and during study Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs Active malignancies or any malignant disease in the past 5 years A chronic or acute disease that in the opinion of the investigator might place the patient at an additional risk, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, or haematological disorders Moderate to severe nasal obstructive diseases such as polyps, septal deviations etc. Clinically significant chronic sinusitis or ocular infection Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma) Use of systemic corticosteroids within 4 weeks of screening Treatment with systemic or local b-blockers Participation in a clinical study with a new investigational drug within the last 3 months or a biological within the last 6 months prior to the study or during the study Pregnancy, lactation or inadequate contraceptive measures (contraceptive measures considered as adequate include appropriate use of oral contraception, i.m. contraception or a contraceptive device) Alcohol, drug, or medication abuse within the past year and during study Any abnormal laboratory parameter at screening that in the opinion of the investigator is considered clinically relevant Lack of co-operation or compliance Severe psychiatric, psychological, or neurological disorders Patients who are employees of the department, 1st grade relatives, or partners of the investigator Expected changes in HDM exposure during the study (avoidance measures, move, etc.)

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br> | Biological: Placebo<br>* Increasing volumes of placebo, will be administered by subcutaneous injection (starting with 0.05 ml) at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of placebo, are given at 4-weekly intervals.<br>|
| Experimental: PURETHAL Mites, 6,667 AU/ml<br> | Biological: PURETHAL Mites 6,667 AU/ml<br>* Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.<br>|
| Experimental: PURETHAL Mites, 20,000 AU/ml<br> | Biological: PURETHAL Mites 20,000 AU/ml<br>* Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.<br>|
| Experimental: PURETHAL Mites, 50,000 AU/ml<br> | Biological: PURETHAL Mites 50,000 AU/ml<br>* Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.<br>|
| Experimental: PURETHAL Mites, 100,000 AU/ml<br> | Biological: PURETHAL Mites 100,000 AU/ml<br>* Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity to House Dust Mite (HDM) allergen assessed by a Nasal Provocation Test |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity to HDM allergen assessed by a Nasal Provocation Test |  | 6 months | 
| Average Adjusted daily Symptom Score (AAdSS) |  | last 2 months of treatment | 
| Peak Nasal Inspiratory Flow (PNIF) |  | at each visit during 1 year treatment | 
| Specific serum IgE, IgG, and IgG4 immunoglobulin concentrations to house dust mite |  | 6 and 12 months treatment | 
| Local and systemic reactions after injection as a measure of Safety and Tolerability |  | 24 hours after each injection during 1 year treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-seasonal allergy, house dust mite, immunotherapy, dose response