Study With High Dose PURETHAL Mites in Allergic Rhinitis/Rhinoconjunctivitis Patients

Study Overview
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Brief Summary
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The aim of the study is to establish the maximum tolerated dose of PURETHAL Mites that is achieved by 90% of the patients with less than 20% of the injections giving rise to a swelling of > 5 cm and the optimal regimen to reach this maximum dose will be determined.

Detailed Description
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The tolerability and safety of three different initial treatment regimens PURETHAL mites in patients with allergic rhinitis / rhinoconjunctivitis induced by house dust mites will be evaluated and the optimal regimen to reach the maximum tolerated dose will be determined. The maximum intended dose is a 4-fold dosage compared to the currently used maintenance dose of PURETHAL Mites. The tolerability and safety of the injections will be examined by means of determining the early and late local and systemic reactions. In addition, short-term efficacy of this high dose PURETHAL mites will be determined by means of the Clinical index score (CIS) and two surrogate efficacy markers; the conjunctival provocation test (CPT) and serum levels of allergen specific immunoglobulins (IgG and IgE). These efficacy parameters are purely indicative and not decisive for the further clinical development of PURETHAL Mites.

Official Title
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Dose Tolerability Study With High Dose PURETHAL Mites in Allergic Rhinitis / Rhinoconjunctivitis Patients

Conditions
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Allergic Rhinitis, Allergic Rhinoconjunctivitis

Intervention / Treatment
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* Drug: PURETHAL Mites 20,000 AUeq/ml
* Drug: PURETHAL Mites 20,000 AUeq/ml
* Drug: PURETHAL Mites 20,000 AUeq/ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with perennial rhinitis or rhinoconjunctivitis, with or without mild asthma (FEV1 > 70%) for at least 2 years. with allergic symptoms related to HDM Positive CPT test to HDM Der p, dose ≤10,000 AUeq/ml Positive SPT to HDM Der p or Der f (mean wheal diameter ≥ 3mm) Specific serum IgE-test (ssIgE > 0.7 U/ml) for HDM Age ≥ 18 years Written informed consent given Exclusion Criteria: Patients with concomitant sensitization i.e. positive SPT (mean wheal diameter ≥ 3 mm) to other allergens than HDM should not be included if they have clinical symptoms at the time of inclusion, related to the other allergen Patients sensitized to pets should not be included if they live together with these pets or have clinical symptoms Immunotherapy (including sublingual) with HDM within the last 5 years Immunotherapy (including sublingual) during the study period Chronic asthma or emphysema, particularly with a FEV1 ≤ 70% of predicted value or use of inhalation corticosteroids Serious immuno-pathologic diseases or malignancies (including auto-immune diseases, tuberculosis) Symptomatic coronary heart diseases or severe (even under treatment) arterial hypertension Diseases with a contra-indication for the use of adrenaline Patients who are using other aluminium preparations, e.g. antacids Severe kidney disease Use of systemic steroids Treatment with systemic and local Beta-blockers or immunosuppressive drugs Active infection of the target organs (nose or eyes) Severe atopic dermatitis in case systemic immunosuppressive medication is used Participation in a clinical study with a new investigational drug within the last 3 months Pregnancy, lactation or inadequate contraceptive measures (adequate contraceptive measures will be the use of a contraceptive device or -pill) Alcohol- or drug abuse Lack of co-operation or severe psychological disorders Institutionalisation by official or judicial order

Ages Eligible for Study
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Minimum Age: 18 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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Slow regimen<br> | Drug: PURETHAL Mites 20,000 AUeq/ml<br>* Group 1: slow regimen (12+2 injections) Initial treatment: incremental weekly dose of 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1.0, 1.2*, 1.6* and 2.0* ml Additional maintenance: 2 two-weekly injections 2.0* ml *Injection volumes larger than 1 ml will be given as 2 separate injections of equal volume within an area of 1 cm.<br>* Other names: Immunotherapy for house dust mites allergy;|
| Other: Intermediate regimen<br> | Drug: PURETHAL Mites 20,000 AUeq/ml<br>* Group 2: intermediate regimen (9+2 injections) Initial treatment: incremental weekly dose of 0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2*, 1.6* and 2.0* ml. Additional maintenance: 2 two-weekly injections 2.0* ml *Injection volumes larger than 1 ml will be given as 2 separate injections of equal volume within an area of 1 cm.<br>* Other names: Immunotherapy for house dust mites allergy;|
| Other: Fast regimen<br> | Drug: PURETHAL Mites 20,000 AUeq/ml<br>* Group 3: fast initial treatment (6+2 injections) Initial treatment: incremental weekly dose of 0.2, 0.4, 0.8, 1.2*, 1.6* and 2.0*ml. Additional maintenance: 2 two-weekly injections 2.0* ml *Injection volumes larger than 1 ml will be given as 2 separate injections of equal volume within an area of 1 cm.<br>* Other names: Immunotherapy for house dust mites allergy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Local Reactions (ELR) occurring 15 minutes after injection. Less than 20% of the injections should give rise to swelling at the injection site of > 5 cm in diameter occurring 15 minutes after injection. |  | 17, 14 or 11 weeks per patient for the respective groups | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late Local Reactions (LLR) occurring within 24 hours after injection, and systemic reactions (SR). General adverse events will be recorded during complete study period. |  | 17, 14 or 11 weeks per patient for the respective groups | 
| Clinical index score (CIS) during the study compared to baseline score (before treatment). |  | weekly during per patient treatment periods of 17, 14 or 11 weeks for the respective groups | 
| Conjunctival provocation test one week after reaching 10,000 AUeq, 20,000 AUeq, or 40,000 AUeq for the respective groups compared to baseline. |  | after 7 weeks of treatment | 
| Conjunctival provocation test 2 weeks after the patients have received two maintenance dosages compared to baseline score. |  | 17, 14 or 11 weeks for the respective treatment groups | 
| Specific IgE and IgG measured 2 weeks after the patients have received two maintenance dosages compared to baseline score. |  | 17, 14 or 11 weeks for the respective treatment groups | 

 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 tolerability