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

Sponsor

Inmunotek S.L. (Industry)

Overall Status

Completed

CT.gov ID

NCT02654223

Collaborator

(none)

180

Enrollment

Locations

Arms

70.1

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Rhinitis Rhinoconjunctivitis	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	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Screening

Official Title:

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

Actual Study Start Date :

Dec 30, 2015

Actual Primary Completion Date :

Nov 1, 2021

Actual Study Completion Date :

Nov 1, 2021

Arms and Interventions

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: 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 Biological: Sublingual placebo Comparison between placebo and active group
Experimental: MG56 Mannosylated 3000 subcutaneous 3000 mTU/mL of subcutaneous immunotherapy and sublingual placebo.	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 Biological: Sublingual placebo Comparison between placebo and active group
Experimental: MG56 Mannosylated 5000 subcutaneous 5000 mTU/mL of subcutaneous immunotherapy and sublingual placebo.	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 Biological: Sublingual placebo Comparison between placebo and active group
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: 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 Biological: Subcutaneous placebo Comparison between placebo and active group
Experimental: MG56 Mannosylated 3000 sublingual 3000 mTU/mL of sublingual immunotherapy and subcutaneous placebo.	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 Biological: Subcutaneous placebo Comparison between placebo and active group
Experimental: MG56 Mannosylated 5000 sublingual 5000 mTU/mL of sublingual immunotherapy and subcutaneous placebo.	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 Biological: Subcutaneous placebo Comparison between placebo and active group
Placebo Comparator: Placebo Sublingual Placebo subcutaneous Sublingual and subcutaneous placebo.	Biological: Subcutaneous placebo Comparison between placebo and active group Biological: Sublingual placebo Comparison between placebo and active group

Outcome Measures

Primary Outcome Measures

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

Dose finding skin prick test [4 months]
Comparison between the beginning and end of the trial and among active groups and placebo
Cytokine production by T cells specific allergen [4 months]
Comparison between the beginning and end of the trial and among active groups and placebo
Immunoglobulin production by B cells specific allergen [4 months]
Comparison between the beginning and end of the trial and among active groups and placebo
Phenotypic and functional analysis of dendritic cells [4 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.
Number of participants with treatment-related adverse events as assessed by MG56-SIT-012 [4 months]
Comparison between the beginning and end of the trial and among active groups and placebo

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clínica Atlas	Aranjuez	Madrid	Spain	28300
2	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid	Spain	28222
3	Hospital Universitario Infanta Elena	Valdemoro	Madrid	Spain	28342
4	Hospital Nisa Aljarafe	Castilleja De La Cuesta	Sevilla	Spain	41950
5	Hospital San Agustín	Dos Hermanas	Sevilla	Spain	41703
6	CLÍNICA Dr. SUBIZA	Madrid		Spain	28006
7	Clínica Ojeda	Madrid		Spain	28006
8	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
9	HOSPITAL UNIVERSITARIO 12 de OCTUBRE	Madrid		Spain	28041
10	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
11	Hospital Viamed Santa Angola de la Cruz	Sevilla		Spain	41013
12	Clínica Alianza Médica	Valladolid		Spain	47001

Sponsors and Collaborators

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, Clínica 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 Ramón y Cajal
Principal Investigator: Antonio Moreno, Clínica Atlas
Principal Investigator: Pedro Guardia, Hospital Universitario Virgen Macarena
Principal Investigator: Agustín Orovigt, Hospital Viamed Santa Ángela 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