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

Phase 2
Completed
Conditions
Rhinitis
Rhinoconjunctivitis
Interventions
Biological: MG56 Mannosylated 500 subcutaneous
Biological: MG56 Mannosylated 5000 sublingual
Biological: MG56 Mannosylated 5000 subcutaneous
Biological: MG56 Mannosylated 500 sublingual
Biological: MG56 Mannosylated 1000 subcutaneous
Biological: MG56 Mannosylated 3000 subcutaneous
Biological: MG56 Mannosylated 3000 sublingual
Biological: MG56 Mannosylated 1000 sublingual
Biological: Subcutaneous placebo
Biological: Sublingual placebo
Registration Number
NCT02654223
Lead Sponsor
Inmunotek S.L.
Brief Summary

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

Detailed Description

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
180
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MG56 Mannosylated 500 sublingualSubcutaneous placebo500 mTU/mL of sublingual immunotherapy and subcutaneous placebo.
MG56 Mannosylated 3000 sublingualSubcutaneous placebo3000 mTU/mL of sublingual immunotherapy and subcutaneous placebo.
MG56 Mannosylated 1000 sublingualSubcutaneous placebo1000 mTU/mL of sublingual immunotherapy and subcutaneous placebo.
MG56 Mannosylated 500 subcutaneousMG56 Mannosylated 500 subcutaneous500 mTU/mL of subcutaneous immunotherapy and sublingual placebo.
MG56 Mannosylated 1000 subcutaneousSublingual placebo1000 mTU/mL of subcutaneous immunotherapy and sublingual placebo.
MG56 Mannosylated 5000 sublingualMG56 Mannosylated 5000 sublingual5000 mTU/mL of sublingual immunotherapy and subcutaneous placebo.
MG56 Mannosylated 5000 subcutaneousMG56 Mannosylated 5000 subcutaneous5000 mTU/mL of subcutaneous immunotherapy and sublingual placebo.
MG56 Mannosylated 500 sublingualMG56 Mannosylated 500 sublingual500 mTU/mL of sublingual immunotherapy and subcutaneous placebo.
MG56 Mannosylated 1000 subcutaneousMG56 Mannosylated 1000 subcutaneous1000 mTU/mL of subcutaneous immunotherapy and sublingual placebo.
MG56 Mannosylated 3000 subcutaneousMG56 Mannosylated 3000 subcutaneous3000 mTU/mL of subcutaneous immunotherapy and sublingual placebo.
MG56 Mannosylated 500 subcutaneousSublingual placebo500 mTU/mL of subcutaneous immunotherapy and sublingual placebo.
MG56 Mannosylated 3000 subcutaneousSublingual placebo3000 mTU/mL of subcutaneous immunotherapy and sublingual placebo.
Placebo Sublingual Placebo subcutaneousSublingual placeboSublingual and subcutaneous placebo.
MG56 Mannosylated 3000 sublingualMG56 Mannosylated 3000 sublingual3000 mTU/mL of sublingual immunotherapy and subcutaneous placebo.
MG56 Mannosylated 5000 subcutaneousSublingual placebo5000 mTU/mL of subcutaneous immunotherapy and sublingual placebo.
MG56 Mannosylated 1000 sublingualMG56 Mannosylated 1000 sublingual1000 mTU/mL of sublingual immunotherapy and subcutaneous placebo.
MG56 Mannosylated 5000 sublingualSubcutaneous placebo5000 mTU/mL of sublingual immunotherapy and subcutaneous placebo.
Placebo Sublingual Placebo subcutaneousSubcutaneous placeboSublingual and subcutaneous placebo.
Primary Outcome Measures
NameTimeMethod
Concentration required to elicit a positive response after nasal provocation test (NPT)4 months

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.

Secondary Outcome Measures
NameTimeMethod
Phenotypic and functional analysis of dendritic cells4 months

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.

Dose finding skin prick test4 months

Comparison between the beginning and end of the trial and among active groups and placebo

Cytokine production by T cells specific allergen4 months

Comparison between the beginning and end of the trial and among active groups and placebo

Immunoglobulin production by B cells specific allergen4 months

Comparison between the beginning and end of the trial and among active groups and placebo

Number of participants with treatment-related adverse events as assessed by MG56-SIT-0124 months

Comparison between the beginning and end of the trial and among active groups and placebo

Trial Locations

Locations (12)

Hospital Nisa Aljarafe

🇪🇸

Castilleja De La Cuesta, Sevilla, Spain

Hospital San Agustín

🇪🇸

Dos Hermanas, Sevilla, Spain

Clínica Atlas

🇪🇸

Aranjuez, Madrid, Spain

Hospital Universitario Puerta de Hierro

🇪🇸

Majadahonda, Madrid, Spain

Hospital Universitario Infanta Elena

🇪🇸

Valdemoro, Madrid, Spain

Hospital Viamed Santa Angola de la Cruz

🇪🇸

Sevilla, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Clínica Alianza Médica

🇪🇸

Valladolid, Spain

CLÍNICA Dr. SUBIZA

🇪🇸

Madrid, Spain

Hospital Universitario Ramón y Cajal

🇪🇸

Madrid, Spain

HOSPITAL UNIVERSITARIO 12 de OCTUBRE

🇪🇸

Madrid, Spain

Clínica Ojeda

🇪🇸

Madrid, Spain

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