Efficacy and Safety Evaluation for the Treatment of Allergy Against Mites

Study Overview
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Brief Summary
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A double-blinded, placebo-controlled, prospective, multicenter randomized of 2 active treatment groups, compared to 1 placebo group, for the determination of the efficacy and safety of subcutaneous immunotherapy in patients with rhinitis/rhinoconjunctivitis with mild to moderate asthma, sensitised to Dermatophagoides pteronyssinus and /or Dermatophagoides farinae.

Detailed Description
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Double blind, multicenter, parallel placebo controlled study. It includes 150 subjects sensitised to mites, from 14 to 65 years of age. Medication treatment of 1 year. The main outcome: CSMS

Official Title
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Randomized, Double-blinded, Placebo-controlled, Prospective, Multicenter Trial to Evaluate the Efficacy and Safety of SIC in Subjects With Mild/Moderate Asthma and Rhinitis/Rhinoconjunctivitis Sensitized to D.Pteronyssinus and/or D. Farinae

Conditions
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Rhinitis, Allergic, Rhinoconjunctivitis, Asthma, Allergic

Intervention / Treatment
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* Biological: 10,000 MM09
* Biological: 30,000 MM09
* Biological: Placebo subcutaneous


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Age between 14 and 65, both genders. Positive suggestive clinical history of controlled intermittent or persistent asthma with intermittent or persistent moderate to severe rhinitis /rhinoconjunctivitis, due to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The diagnosis of asthma will be valid from 12 months prior to signing the informed consent form Subjects with a positive skin prick-test wheal size >5 mm higher diameter due to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The positive and negative control of the test should give consistent results Specific immunoglobulin E against house dust mites >3,5 KU/mL (InmunoCAP® o Immulite), for the complete extract of Dermatophagoides pteronyssinus and / or for Dermatophagoides farinae or for some of the molecular components of these allergenic sources Subjects should preferably be monosensitized to the study allergens. In case of subjects sensitized to other aeroallergens, only those with the following characteristics may be included in the study: Subjects with positive skin test to Blomia tropicalis and Lepidoglyphus destructor, whose specific IgE values do not exceed or equal the values for the study allergens. The maximum specific IgE value for these allergens is 3.5 KU/L. Subjects with positive skin tests to epithelia, as long as they present occasional exposure and symptomatology. Subjects with positive skin tests to pollens, whose specific IgE values do not exceed or equal the values of the allergens in the study and who do not present exacerbations during the pollen season. The maximum value of specific IgE for these allergens is 17.5 KU/L. Women of childbearing age (from menarche) must present a urine pregnancy test with a negative result at the time of joining the trial, before the first administration of the IMP. Women of childbearing age participating in the trial must agree to use an appropriate method of contraception, meaning any act, device, or medication to prevent conception or viable pregnancy, during the trial if they are sexually active. Subjects with a diagnosis of asthma according to the GEMA 5.0 guideline. Subjects capable of complying with the dosing regimen. Subjects who own an smartphone for symptom registration and medication Exclusion Criteria: Subjects with positive prick test to fungus, whose specific IgE is <0,35 KU/L Subjects with positive prick test to epiteliums, whose specific IgE is <0,35 KU/L Subjects who have received prior immunotherapy in the preceding 5 years for any of the epiteliums, fungus and dust mites. Subjects in which immunotherapy may be subject to an absolute general contraindication according to the criteria of the Immunotherapy Committee of the Spanish Society of Allergy and Clinical Immunology and the European Allergy and Clinical Immunology Immunotherapy Subcommittee. Subjects with severe or uncontrolled intermittent or persistent asthma, with an FEV1 <70% with respect to the reference value despite adequate pharmacological treatment at the time of inclusion in the trial. Likewise, subjects with intermittent or persistent rhinitis / rhinoconjunctivitis with severe symptoms in which the suspension of oral or systemic antihistamine treatment is contraindicated. Subjects who have previously presented a serious secondary reaction during the performance of diagnostic skin tests using the prick test. Subjects under treatment with β-blockers. Clinically unstable subjects at the time of inclusion in the trial (acute asthma exacerbation, respiratory infection, feverish process, acute urticaria, etc.). Subjects with active chronic urticaria, severe dermography, severe atopic dermatitis, sunburn, active psoriasis with lesions in areas where skin tests are performed, or a history of hereditary angioedema. Subjects that have some pathology in which the administration of adrenaline is contraindicated (hyperthyroidism, hypertension, heart disease, etc.). Subjects with some other disease not related to moderate rhinoconjunctivitis or asthma, but of potential severity and that may interfere with treatment and follow-up (epilepsy, psychomotor disorder, uncontrolled diabetes, malformations, multiple operations, kidney disease,). Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumor diseases or with a diagnosis of immunodeficiencies. Subject whose status prevents him from offering cooperation and or who has severe psychiatric disorders. Subjects with a known allergy to other components of the investigational medicinal product other than the allergen. Subjects with diseases of the lower respiratory tract other than asthma such as emphysema or bronchiectasis. Direct investigator's relatives. Pregnant women or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 14 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
Interventional Model Description: Randomized, double-blind, placebo-controlled, multi centre, parallel-group study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental:10,000 MM09<br>10,000 TU/mL of subcutaneous immunotherapy | Biological: 10,000 MM09<br>* Purified allergenic extract, and adsorbed in aluminum hydroxide and polymerized with glutaraldehyde, mite mixture (Dermatophagoides pteronyssinus and Dermatophagoides farinae) with a concentration of 10,000 UT / mL<br>|
| Experimental: Experimental: 30,000 MM09<br>30,000 TU/mL of subcutaneous immunotherapy | Biological: 30,000 MM09<br>* Purified allergenic extract, and adsorbed in aluminum hydroxide and polymerized with glutaraldehyde, mite mixture (Dermatophagoides pteronyssinus and Dermatophagoides farinae). The concentration is 30,000 UT / mL<br>|
| Placebo Comparator: Placebo subcutaneous<br>The same solution and presentation as the active treatment, but without any active ingredients. | Biological: Placebo subcutaneous<br>* The same solution and presentation as the active treatment, but without active ingredients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSMS: Combined Symptoms and Medication Score | Evaluation of the number of symptoms and the consumption of medication necessary for the control of such symptoms in asthma and rhinitis / rhinoconjunctivitis of each subject during the trial, of the groups with each other and with respect to placebo. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication-free days | Number of days that the subjects need no medication | 12 months | 
| Symptom-free days | Number of days that the subjects have no symptom | 12 months | 
| Number of participants with treatment-related adverse events as assessed by MM09-SIT-023 | Comparison between the beginning and end of the trial and among active groups and placebo | 12 months | 
| Quality of life associated with asthma | The quality of life associated with asthma will be measured following the GINA questionnaire. The GINA questionnaire consists of 4 questions. In questions 1-4, patients recall their experience during the last 4 weeks and answer using YES or NO. The interpretation of the answers is as follows: Well-controlled: None of the answers are YES Partly controlled: 1 - 2 answers are YES Uncontrolled: 3-4 answers are YES | 12 months | 
| Quality of life associated with rhinitis | The quality of life associated with rhinitis will be measured following the test ESPRINT-15. The scoring of the questionnaire will be carried out as follows: The global sum of the scores (ranging from 0 = nothing has bothered me to 6 = it has bothered me a lot) of the 14 items plus the score given in the general questionnaire (ranging from 0 = Excellent to 4 = Bad). This sum is divided by the total number of items (15 items). The interpretation of the scores is between 0 (low impact) and 6 (high impact). | 12 months | 
| Visual Analogue Scale (VAS) | Visual Analogue Scale in which the subject has to indicate how he/she feels regarding to his allergy symptoms at the moment from 1 to 10. Being 1 very bad and 10 very well. | 12 months | 
| Immunological parameters | Analyses of total Ig3 and specific IgA,IgG and IgG4 | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rhinitis/ Rhinoconjunctivitis, Mild to moderate asthma, Allergy, Immunotherapy, Mites