Dose Finding for the Treatment of Rhinitis/Rhinoconjunctivitis Against Grass Pollen Allergy

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the more efficient dose for the treatment of rhinitis/rhinoconjunctivitis against grass pollen allergy

Detailed Description
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Double blind placebo-controlled study. The subjects will receive medication during 4 months.

Official Title
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Double Blind, Placebo-controlled, Dose Finding, Prospective, Multicenter Clinical Trial for the Treatment of Rhinitis/Rhinoconjunctivitis Against Grass Pollen Allergy

Conditions
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Rhinitis, Rhinoconjunctivitis

Intervention / Treatment
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* Biological: MG56 Mannosylated 500 subcutaneous
* Biological: MG56 Mannosylated 1000 subcutaneous
* Biological: MG56 Mannosylated 3000 subcutaneous
* Biological: MG56 Mannosylated 5000 subcutaneous
* Biological: MG56 Mannosylated 500 sublingual
* Biological: MG56 Mannosylated 1000 sublingual
* Biological: MG56 Mannosylated 3000 sublingual
* Biological: MG56 Mannosylated 5000 sublingual
* Biological: Subcutaneous placebo
* Biological: Sublingual placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Positive suggestive clinical history of intermittent or persistent moderate to severe rhinitis /rhinoconjunctivitis, with or without moderate asthma, due to grass pollen allergy Subjects with a positive skin prick-test (wheal sixe >6 mm diameter) Specific immunoglobulin E (IgE, CAP >3) to grass pollen Age between 14 and 65 years Both genders Subjects capable of giving informed consent Subjects capable of complying with the dosing regimen Subjects that have not received immunotherapy in the last 5 years Subjects presenting sensitization to another aeroallergens and or mites, cats or dogs, but that is considered clinically not relevant or no clinical interference with the nasal provocation test. Exclusion Criteria: Subjects outside of the age range. Subjects who have previously received immunotherapy for the treatment of the allergic rhinitis/rhinoconjunctivitis due to grass pollen and other allergens in the last 5 years. Subjects that immunotherapy may be an absolute contraindication according to the criteria of the immunotherapy Committee of the Spanish society of Allergy and Clinical Immunology, and of the European Allergy and Clinical Immunology Immunotherapy Subcommittee may also include. Subjects with important symptoms of rhinoconjunctivitis /bronchial asthma in which the suspension of the systemic antihistamine treatment is contraindicated. Subjects with persistent severe or not controlled asthma , with a forced expiratory volume (FEV) < 70 respect to the reference value in spite of the appropriate pharmacological treatment at the time of the inclusion in the trial. Subjects that have required oral corticosteroids in the 12 weeks previous to the inclusion in the trial. Subjects that have previously submitted a serious secondary reaction during the skin prick test Subjects in treatment with beta blockers. Unstable subjects from the clinical point of view (respiratory infection, febrile, acute urticaria, etc.) at the time of the inclusion in the clinical trial Subject with chronic urticaria in the last 2 years or hereditary angioedema. Subjects that have some pathology (hyperthyroidism, hypertension, heart disease, etc.) is contraindicated. Subjects with any other disease not associated with the rhinitis/rhinoconjunctivitis, but of potential severity and that could interfere with treatment and follow-up (epilepsy, psychomotor deterioration, diabetes, malformations, multi-operated, kidney diseases,...). Subjects with autoimmune disease (lupus, thyroiditis, etc.), tumor or with diagnosis of immunodeficiency diseases. Subject whose status prevents him from providing cooperation and or which present severe psychiatric disorders. Subject with known allergy to other components of the vaccine different from pollen of grasses. Subjects with lower airway diseases other than asthma such as emphysema or bronchiectasis. Direct investigator's relatives. Pregnant or women at risk of pregnancy and 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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MG56 Mannosylated 500 subcutaneous<br>500 mTU/mL of subcutaneous immunotherapy and sublingual placebo. | Biological: MG56 Mannosylated 500 subcutaneous<br>* Mixture of the following pollens: Phleum pratense, Dactylis glomerata, allergen extract with a concentration of 500 mTU (Mannosylated Therapeutic Units)/ml subcutaneous<br>Biological: Sublingual placebo<br>* Comparison between placebo and active group<br>|
| Experimental: MG56 Mannosylated 1000 subcutaneous<br>1000 mTU/mL of subcutaneous immunotherapy and sublingual placebo. | Biological: MG56 Mannosylated 1000 subcutaneous<br>* Mixture of the following pollens: Phleum pratense, Dactylis glomerata, allergen extract with a concentration of 1000 mTU (Mannosylated Therapeutic Units)/ml subcutaneous<br>Biological: Sublingual placebo<br>* Comparison between placebo and active group<br>|
| Experimental: MG56 Mannosylated 3000 subcutaneous<br>3000 mTU/mL of subcutaneous immunotherapy and sublingual placebo. | Biological: MG56 Mannosylated 3000 subcutaneous<br>* Mixture of the following pollens: Phleum pratense, Dactylis glomerata, allergen extract with a concentration of 3000 mTU (Mannosylated Therapeutic Units)/ml subcutaneous<br>Biological: Sublingual placebo<br>* Comparison between placebo and active group<br>|
| Experimental: MG56 Mannosylated 5000 subcutaneous<br>5000 mTU/mL of subcutaneous immunotherapy and sublingual placebo. | Biological: MG56 Mannosylated 5000 subcutaneous<br>* Mixture of the following pollens: Phleum pratense, Dactylis glomerata, allergen extract with a concentration of 5000 mTU (Mannosylated Therapeutic Units)/ml subcutaneous<br>Biological: Sublingual placebo<br>* Comparison between placebo and active group<br>|
| Experimental: MG56 Mannosylated 500 sublingual<br>500 mTU/mL of sublingual immunotherapy and subcutaneous placebo. | Biological: MG56 Mannosylated 500 sublingual<br>* Mixture of the following pollens: Phleum pratense, Dactylis glomerata, allergen extract with a concentration of 500 mTU (Mannosylated Therapeutic Units)/ml sublingual<br>Biological: Subcutaneous placebo<br>* Comparison between placebo and active group<br>|
| Experimental: MG56 Mannosylated 1000 sublingual<br>1000 mTU/mL of sublingual immunotherapy and subcutaneous placebo. | Biological: MG56 Mannosylated 1000 sublingual<br>* Mixture of the following pollens: Phleum pratense, Dactylis glomerata, allergen extract with a concentration of 1000 mTU (Mannosylated Therapeutic Units)/ml sublingual<br>Biological: Subcutaneous placebo<br>* Comparison between placebo and active group<br>|
| Experimental: MG56 Mannosylated 3000 sublingual<br>3000 mTU/mL of sublingual immunotherapy and subcutaneous placebo. | Biological: MG56 Mannosylated 3000 sublingual<br>* Mixture of the following pollens: Phleum pratense, Dactylis glomerata, allergen extract with a concentration of 3000 mTU (Mannosylated Therapeutic Units)/ml sublingual<br>Biological: Subcutaneous placebo<br>* Comparison between placebo and active group<br>|
| Experimental: MG56 Mannosylated 5000 sublingual<br>5000 mTU/mL of sublingual immunotherapy and subcutaneous placebo. | Biological: MG56 Mannosylated 5000 sublingual<br>* Mixture of the following pollens: Phleum pratense, Dactylis glomerata, allergen extract with a concentration of 5000 mTU (Mannosylated Therapeutic Units)/ml sublingual<br>Biological: Subcutaneous placebo<br>* Comparison between placebo and active group<br>|
| Placebo Comparator: Placebo Sublingual Placebo subcutaneous<br>Sublingual and subcutaneous placebo. | Biological: Subcutaneous placebo<br>* Comparison between placebo and active group<br>Biological: Sublingual placebo<br>* Comparison between placebo and active group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration required to elicit a positive response after nasal provocation test (NPT) | Change in the threshold concentration of grass allergen extract, measured in Histamine Equivalent Prick per ml (HEP/ml), needed to trigger a positive response after nasal provocation test (NPT) assessed by acoustic rhinometry. This will be compared between the beginning and end of the trial and among active groups and placebo. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose finding skin prick test | Comparison between the beginning and end of the trial and among active groups and placebo | 4 months | 
| Cytokine production by T cells specific allergen | Comparison between the beginning and end of the trial and among active groups and placebo | 4 months | 
| Immunoglobulin production by B cells specific allergen | Comparison between the beginning and end of the trial and among active groups and placebo | 4 months | 
| Phenotypic and functional analysis of dendritic cells | Will be analyzed changes in the frequency of plasmacytoid dendritic cells, myeloid dendritic cell and Treg cells in peripheral blood, between the beginning and end of the trial and among active groups and placebo The frequencies of peripheral blood mononuclear cells in each of the above populations is determined before and after treatment with mannosylated polymers by flow cytometry after staining with specific antibodies. | 4 months | 
| Number of participants with treatment-related adverse events as assessed by MG56-SIT-012 | Comparison between the beginning and end of the trial and among active groups and placebo | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rhinitis / Rhinoconjunctivitis, Vaccine, Immunotherapy, Grass pollen, Allergy