Dose Finding for the Treatment of Rhinitis/Rhinoconjunctivitis Against Grass Pollen Allergy (MG56)

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

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

Study Overview

• Status: Completed
• Conditions: Rhinitis; Rhinoconjunctivitis
• Intervention / Treatment: Biological: MG56 Mannosylated 500 subcutaneous; Biological: Sublingual placebo; Biological: MG56 Mannosylated 1000 subcutaneous; Biological: MG56 Mannosylated 3000 subcutaneous; Biological: MG56 Mannosylated 5000 subcutaneous; Biological: MG56 Mannosylated 500 sublingual; Biological: Subcutaneous placebo; Biological: MG56 Mannosylated 1000 sublingual; Biological: MG56 Mannosylated 3000 sublingual; Biological: MG56 Mannosylated 5000 sublingual

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28006
    • CLÍNICA Dr. SUBIZA
  • Madrid, Spain, 28006
    • Clinica Ojeda
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Sevilla, Spain, 41013
    • Hospital Viamed Santa Angola de la Cruz
  • Valladolid, Spain, 47001
    • Clínica Alianza Médica
  • Madrid
    • Aranjuez, Madrid, Spain, 28300
      • Clínica Atlas
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
    • Valdemoro, Madrid, Spain, 28342
      • Hospital Universitario Infanta Elena
  • Sevilla
    • Castilleja De La Cuesta, Sevilla, Spain, 41950
      • Hospital Nisa Aljarafe
    • Dos Hermanas, Sevilla, Spain, 41703
      • Hospital San Agustín

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Inmunotek S.L.
• Investigators: Principal Investigator: Javier Subiza, PhD; MD, Clinica Subliza; Principal Investigator: Carmen Diéguez, PhD; MD, Hospital Universitario 12 de Octubre; Study Director: Pedro Ojeda, PhD; MD, Clinica Ojeda; Principal Investigator: Javier Ruiz Hornillos, PhD; MD, Hospital Universitario Infanta Elena; Principal Investigator: Matilde Domínguez, PhD; MD, Hospital Universitario Puerta de Hierro; Principal Investigator: Emilio Solano, MD, Hospital Universitario Ramon Y Cajal; Principal Investigator: Antonio Moreno, Clínica Atlas; Principal Investigator: Pedro Guardia, Hospital Universitario Virgen Macarena; Principal Investigator: Agustín Orovigt, Hospital Viamed Santa Angela De la Cruz; Principal Investigator: Alberto Caso, Hospital San Agustín; Principal Investigator: Alicia Alonso, Clínica Alianza Médica; Principal Investigator: Amparo Conde, Hospital Nisa Sevilla Aljarafe

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2015
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: December 22, 2015
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (Estimate): January 13, 2016

Study Record Updates

• Last Update Posted (Actual): January 27, 2022
• Last Update Submitted That Met QC Criteria: January 12, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Allergy; Vaccine; Immunotherapy; Grass pollen; Rhinitis / Rhinoconjunctivitis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Nose Diseases; Conjunctival Diseases; Rhinitis, Allergic; Hypersensitivity; Rhinitis; Rhinitis, Allergic, Seasonal; Conjunctivitis
• Other Study ID Numbers: MG56-SIT-012; 2014-005471-88 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No