Efficacy and Safety Evaluation for the Treatment of Allergy Against Grass and Olive Pollen

Study Overview
=================
Brief Summary
-----------------
Prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial of efficacy and safety with subcutaneous immunotherapy in patients with mild to moderate rhinitis / rhinoconjunctivitis with or without mild to moderate asthma sensitized to grasses and olive

Detailed Description
-----------------
Double blind, multicenter, parallel, placebo controlled study. It includes 180 subjects sensitised to olea and grass pollen with mild to moderate rhinitis / rhinoconjunctivitis with or without mild to moderate asthma, from 12 to 65 years of age. Medication treatment during 1 year. The main outcome: CSMS

Official Title
-----------------
A Randomized, Double-Blinded, Placebo-Controlled, Prospective, Multicenter CT to Evaluate Efficacy and Safety of Subcutaneous Immunotherapy in Subjects With Rhinitis With/Without Mild to Moderate Asthma Sensitized to Olive and Grass Pollen

Conditions
-----------------
Rhinitis, Allergic, Rhinoconjunctivitis, Asthma, Allergic

Intervention / Treatment
-----------------
* Biological: 10,000 MG01 + 10,000 T517
* Biological: 30,000 MG01 + 10,000 T517
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject who has signed the informed consent. Subjects of both sexes aged between 12 and 65 years. Subjects with confirmed clinical history of inhalational allergy (rhinitis and / or moderate-severe intermittent or persistent rhinoconjunctivitis according to the ARIA classification with or without intermittent or persistent controlled mild-moderate asthma according to the GEMA 5.0 classification caused by grass and olive allergy. The diagnosis of asthma will be valid from 12 months prior to signing the informed consent Subjects with a positive prick test (higher papule diameter ≥ 5 mm) to a standardized extract of pollen from grasses (Phleum pratense, Holcus lanatus, Dactylis glomerata, Poa pratensis, Festuca elatior, Lolium perenne), or one of the components of the mixture and an olive extract. Specific IgE (CAP or Immulite) against a mixture of grasses or against one of the components of the mixture of grasses, preferably Phleum pratense and olive or one of the molecular components of allergenic sources with a value > 3,5 KU / L. Women of childbearing age (from menarche) should submit a urine pregnancy test with a negative result at the time of joining the trial. Women of childbearing potential, and men participating in the trial, should commit to using an appropriate method of contraception. Medically acceptable methods of contraception are intrauterine devices placed at least 3 months in advance, surgical sterilization (for example, tubal ligation), barrier methods, or the use of oral contraceptives. Subjects capable of complying with the dosage regimen. Subjects who have a smartphone to record symptoms and medication. Subjects with a negative prick test to coestational pollens. In the case specific IgE is available, the result should be <3,5 kU/L and without relevant symptomatology Subjects with a negative prick test to other aeroallergens (dust mites, epitheliums and fungus). In the case specific IgE is available, the result should be <3,5 kU/L and without relevant symptomatology Exclusion Criteria: Subjects polysensitized to other aeroallergens with the exception of epithelia with occasional exposure and symptoms Subjects polysensitized to other aeroallergens with the exception non-seasonal pollens with grasses and olive Subjects who have received prior immunotherapy in the preceding 5 years to any aeroallergens. 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 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 ß-blockers. Clinically unstable subjects at the time of enrolment in the trial (acute asthma exacerbation, respiratory infection, feverish process, acute urticaria, etc.). Subjects with active chronic urticaria, severe dermographism, severe atopic dermatitis, sunburns, active psoriasis with lesions in areas where skin tests will be performed, or a history of hereditary angioedema. Subjects who have any pathology in which the administration of adrenaline is contraindicated (hyperthyroidism, HT, 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 condition prevents him / her from offering cooperation and who has severe psychiatric disorders. Subjects with a known allergy to other investigational drug components other than the allergen. Subjects with diseases of the lower respiratory tract other than asthma such as emphysema or bronchiectasis. Subjects who are direct relatives of the researchers. Pregnant or lactating women.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized, double-blind, placebo-controlled, multicentre, parallel-group study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10,000 MG01 + 10,000 T517<br>10,000 TU/mL of MG01 + 10,000 TU/mL of T517 of subcutaneous immunotherapy | Biological: 10,000 MG01 + 10,000 T517<br>* Purified and polymerized with glutaraldehyde allergen extract, from a mixture of grasses (Phleum pratense, Holcus lanatus, Poa pratensis, Festuca pratensis, Lolium perenne and Dactylis glomerata) and Olea (Olea europaea), adsorbed on aluminum hydroxide. The other ingredients are: sodium chloride (0.9%), phenol (0.4%) and water for injections<br>* Other names: Grasses and olea 10,000;|
| Experimental: 30,000 MG01 + 10,000 T517<br>30,000 TU/mL of MG01 + 10,000 TU/mL of T517 of subcutaneous immunotherapy | Biological: 30,000 MG01 + 10,000 T517<br>* Purified and polymerized with glutaraldehyde allergen extract, from a mixture of grasses (Phleum pratense, Holcus lanatus, Poa pratensis, Festuca pratensis, Lolium perenne and Dactylis glomerata) and Olea (Olea europaea), adsorbed on aluminum hydroxide. The other ingredients are: sodium chloride (0.9%), phenol (0.4%) and water for injections<br>* Other names: Grasses and olea;|
| Placebo Comparator: Placebo subcutaneous<br>The same solution and presentation as the active treatment, but without active ingredients. | Other: Placebo<br>* The same solution and presentation as the active treatment, but without active ingredients<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSMS: Combined Symptoms and Medication Score | Overall score of symptoms and medication throughout the trial. The minimum score is cero and maximum six, per day | 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 | 
| Asthmatic exacerbations | Time elapsed until the first appearance of asthmatic exacerbations | 12 months | 
| Visual Analogue Scale (VAS) | Visual Analogue Scale in which the subject has to indicate in a straight line of 10cm how he/she feels regarding to his allergy symptoms. Being left side very bad and right side very well | 12 months | 
| Quality of life rhinitis test | Quality of life rhinitis test (ESPRINT-15) | 12 months | 
| Quality of life asthma test | Control of asthma by Asthma Control Quality questionnaire | 12 months | 
| Health resources | For each patient, the number of times that due to allergy symptoms has done the following will be counted: Have visited the GP, Have made an unscheduled visit to the specialist, Has gone to the emergency room, Has been hospitalized, Have needed to contact the doctor by phone | 12 months | 
| Immunological parameters | Analyses of total and specific IgE, specific Ig G4 | 12 months | 
| Security parameters | Global rate and severity of AE per administration and per subject | 12 months | 
| Adverse Reactions | Local and systemic reactions and any medication administered for the treatment of AR | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Allergy, Rhinitis/ Rhinoconjunctivitis, Mild to moderate asthma, Grasses, Olea