Efficacy and Safety Evaluation of the Treatment of Allergy Against Cupressaceae and Grasses.

Study Overview
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Brief Summary
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A Randomized, Double-Blinded, Placebo-Controlled, Prospective, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Immunotherapy in Patients With Rhinitis With or Without Mild to Moderate Asthma Sensitized to cupressaceae and grasses.

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

Official Title
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A RDPC, Prospective, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of SCIT in Patients With Rhinitis With or Without Mild to Moderate Asthma Sensitized to Cupressaceae and Grasses.

Conditions
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Rhinitis, Allergic, Rhinoconjunctivitis, Asthma, Allergic

Intervention / Treatment
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* Biological: 10,000 MG01 +10,000 T521
* Biological: 30,000 MG01 +10,000 T521
* Other: Placebo subcutaneous


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Aged between 12 and 65, both genders Positive suggestive clinical history of intermittent or persistent moderate to severe rhinitis /rhinoconjunctivitis according to ARIA classification, with or without moderate intermittent or persistent asthma,according to GEMA 5.0, due to grass and cupressaceae pollen. Subjects with a positive skin prick-test (wheal size >5 mm diameter) to a standardized grass pollen extract (Phleum pratense, Holcus lanatus, Dactylis glomerata, Poa pratensis, Festuca elatior, Lolium perenne) or to a one extract of the mixture and to a cupressaceae extract. Specific IgE ≥ 3,5 KU/L , against grass (preferably Phleum pratense) and cupressaceae pollen (InmunoCAP® o Immulite). Women of childbearing age (from menarche) must present a urine pregnancy test with a negative result at the time of joining the trial. Women of childbearing potential 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 dosing regimen. Subjects who own a smartphone for symptom registration 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 with positive prick test to other aeroallergens except for sensitisation to epithelia with occasional exposure and symptoms. Subjects with positive prick test to other aeroallergens except for sensitisation to pollen noncoseasonal with cupressus or grasses. Subjects who have received prior immunotherapy in the preceding 5 years for any of the allergens tested or a cross-reactive allergen or are currently receiving immunotherapy with any allergen. 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 had a severe secondary reaction during the prick test diagnostic skin test. Subjects treated with beta-blockers. Clinically unstable subjects at the time of inclusion in the trial (acute asthmatic exacerbation, respiratory infection, febrile process, acute urticaria, etc.). Subjects with active chronic urticaria, severe dermographism, severe atopic dermatitis, sunburn, 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 adrenaline administration is contraindicated (hyperthyroidism, HTN, heart disease, etc.). Subjects with any other disease not related to moderate rhinoconjunctivitis or asthma, but potentially serious and that may interfere with treatment and follow-up (epilepsy, psychomotor disorder, uncontrolled diabetes, malformations, multioperated patients, kidney disease,). Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumor diseases or with a diagnosis of immunodeficiencies. Subject whose condition prevents from offering cooperation and/ or who has severe psychiatric disorders. Subjects with a known allergy to components of the investigational medicinal product other than the allergen. Subjects with lower respiratory diseases other than asthma such as emphysema or bronchiectasis. Subjects who are direct relatives of the researchers. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 12 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, multicentre, parallel-group study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10,000 MG01 + 10,000 T521<br>10,000 TU/mL of MG01 + 10,000 TU/mL of T521 of subcutaneous immunotherapy | Biological: 10,000 MG01 +10,000 T521<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 cupressaceae (Juniperus oxycedrus), adsorbed on aluminum hydroxide. The other ingredients are: sodium chloride (0.9%), phenol (0.4%) and water for injections<br>|
| Experimental: 30,000 MG01 + 10,000 T521<br>30,000 TU/mL of MG01 + 10,000 TU/mL of T521 of subcutaneous immunotherapy | Biological: 30,000 MG01 +10,000 T521<br>* Purified allergen extract polymerized with glutaraldehyde, from a mixture of grasses (Phleum pratense, Holcus lanatus, Poa pratensis, Festuca pratensis, Lolium perenne and Dactylis glomerata) and cupressaceae (Juniperus oxycedrus), adsorbed on aluminum hydroxide. The other ingredients are: sodium chloride (0.9%), phenol (0.4%) and water for injections.<br>|
| Placebo Comparator: Placebo subcutaneous<br>The same solution and presentation as the active treatment, but without active ingredients. | Other: 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, asthma and rhinitis. | 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 | Both rhinitis/rhinoconjunctivitis and asthma | 12 months | 
| Symptom free days | Both rhinitis/rhinoconjunctivitis and asthma | 12 months | 
| Number of participants with treatment-related adverse events as assessed by T521+MG01-SIT026 | 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 ACQ questionnaire. The ACQ questionnaire consists of 6 questions (ACQ-6). In questions 1-6, patients recall their experience during the last 7 days and answer using a scale of 7 points (from 0 = fully controlled to 6 = extremely poorly controlled). The questionnaire score is the mean of the 6 responses (ACQ-6). The interpretation of the scores is as follows: Less than or equal to 0.75: Adequate control of asthma From 0.75 to 1.50: Partially controlled asthma More than 1.50: Inadequate asthma control | 12 months | 
| 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 (0) = very bad and right side (10) = very well | 12 months | 
| Asthmatic exacerbations | Time elapsed until the first appearance of asthmatic exacerbations, number, duration and severity. | 12 months | 
| Health resource consumption | Counting the Health resource consumption: visits to specialists, telephone calls, test and analyses. | 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 | 

 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, Grass, cupressaceae