Prospective, randomized, placebo-controlled, multi-center trial comparing the efficacy and safety of subcutaneous immunotherapy with a mixture of grasses and mites at adequate doses versus monotherapy, for the treatment of allergy

INTERVENTION: Product Name: MM09‐MG01(30.000‐30.000) Pharmaceutical Form: Suspension for injection INN or Proposed INN: N/A Current Sponsor code: MG01 Other descriptive name: Mixture of polymerized with glutaraldehyde allergen extracts of Phleum pratense, Dactylis glomerata, Poa pratensis, Holcus lanatus, Festuca elatior and Lolium perenne Concentration unit: AU/ml allergy unit(s)/millilitre Concentration type: equal Concentration number: 30.000‐ INN or Proposed INN: N/A Current Sponsor code: MM09 Other descriptive name: Mixture of polymerized with glutaraldehyde allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae Concentration unit: AU/ml allergy unit(s)/millilitre Concentration type: equal Concentration number: 30.000‐ Pharmaceutical form of the placebo: Suspension for injection Route of administration of the placebo: Subcutaneous use Product Name: MG01(30.000) Pharmaceutical Form: Suspension for injection INN or Proposed INN: N/A Current Sponsor code: MG01 Other descriptive name: Mixture of polymerized with glutaraldehyde allergen extracts of Phleum pratense, Dactylis glomerata, Poa pratensis, Holcus lanatus, Festuca elatior and Lolium perenne Concentration unit: AU/ml allergy unit(s)/millilitre Concentration type: equal Concentration number: 30.000‐ Pharmaceutical form of the placebo: Suspension for injection Route of administration of the placebo: Subcutaneous use Product Name: MM09(30.000) Pharmaceutical Form: Suspension for injection INN or Proposed INN: N/A Current Sponsor code: MM09 Other descriptive name: Mixture of polymerized with glutaraldehyde allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae Concentration unit: AU/ml allergy unit(s)/millilitre Concentration type: equal Concentration number: 30.000‐ Pharmac CONDITION: Mild to moderate asthma and allergic rhinitis / rhinoconjunctivitis (intermittent or persistent) due to hypersensitivity to house dust mites (Dermatophagoides pteronyssinus and / or D. farinae) and grass pollen. ; MedDRA version: 20.0 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853 ; MedDRA version: 21.1 Level: LLT Classification code 10034382 Term: Perennial allergic rhinitis System Organ Class: 100000004855 ; MedDRA version: 20.0 Level: LLT Classification code 10020419 Term: House dust mite allergy System Organ Class: 100000004870 ; MedDRA version: 20.0 Level: LLT Classification code 10036019 Term: Pollen allergy System Organ Class: 100000004870 Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: To evaluate the clinical efficacy of subcutaneously administered polymerized allergenic extracts, compared to placebo, in subjects with controlled intermittent or persistent (mild‐moderate) asthma, with allergic (intermittent or persistent) rhinitis / rhinoconjunctivitis, polysensitized to mites and grasses, using combined score and consumption of medication for asthma and rhinitis / rhinoconjunctivitis for each trial subject. Primary end point(s): Score of symptoms and medication throughout the trial, for both asthma and rhinitis/rhinoconjunctivitis. Secondary Objective: To assess the safety and indirect efficacy of polymerized allergenic extracts administered subcutaneously, under the conditions mentioned above, by comparisons between active groups and placebo, both at the beginning and at the end of the trial, on the secondary variables:; ‐Symptom‐free and medication‐free days for asthma and rhinitis.; ‐FEV1 and PEF measurement; ‐Time elapsed until the first appearance of asthmatic exacerbations, number, duration and severity.; ‐Immunological parameters (total and specific IgE, specific IgE index / total IgE specific IgE for relevant allergens, specific IgG and specific IgG4).; ‐Analog visual scale.; ‐Quality of life using ESPRINT‐15 questionnaires.; ‐Control of asthma by ACT test.; ‐Consumption of health resources.; ‐Global rate and severity of AE per administration and per subject.; ‐Reactions at the administration site and any medication administered for the treatment of AE. Timepoint(s) of evaluation of this end point: Beginning and end of the trial SECONDARY OUTCOME: Secondary end point(s): A quantitative comparison will be made both at the beginning and at the end of the trial for each subject and between the different groups of active treatment and placebo (group treated with extract of mites and group treated with extract of grass pollen compared with group treated with mixture of the two allergens (mites and grasses) and both against placebo) of the following parameters:; ; ‐ In asthma: Symptom‐free days and Medication‐free days; ‐ In rhinitis: Symptom‐free days and medication‐free days; ‐ Measurement of FEV1 and PEF; ‐ Time elapsed until the first appearance of asthmatic exacerbations, number, duration and severity.; ‐ Severity of symptoms of rhinitis / rhinoconjunctivitis and its evolution during the study period; ‐ Immunological parameters:; 1. Total IgE, specific IgE, IgE specific to relevant allergens; 2. Specific IgG and specific IgG4; 3. Specific IgE / total IgE index; ‐ Analog visual scale; ‐ Asthma Control Test (ACT) ; ‐ Quality of life questionnaire for rhinitis ESPRINT‐15; ‐ Consumption of health resources; ‐ Security variables:; 1. Overall rate, severity and ratio of any AE by administration and by subject.; ? 2. Assessment of local tolerability, administration site reactions, and any medications administered for the treatment of AE. Timepoint(s) of evaluation of this end point: Beginning and end of the trial INCLUSION CRITERIA: 1. Subjects who have signed the informed consent 2. Subjects with a confirmed medical history of asthma (intermittent or persistent mild‐moderate, controlled), as defined by GEMA 5 with rhinitis / rhinoconjunctivitis (intermittent or persistent) according to the ARIA classification caused by polysensitization to grass pollen and mites (D. pteronyssinus and / or D. farinae). 3. Subjects with a positive prick test (average diameter of the papule = to 5 mm) to a standardized extract of grass pollen mixture, or to one of the components of the mixture (Dactilys glomerata, Poa pratensis, Holcus lanatus, Festuca elatior, Phleum pratense and Lolium perenne) and to an extract of D. pteronyssinus and / or D. farinae, tested within the 12 months prior to signing the informed consent. 4. Specific IgE (CAP or Immulite) against one of the components of the mixture of grasses, preferably Phleum pratense and mites (D. pteronyssinus and / or D. farinae) or one or more o