Clinical trial NCT02661854: Dose Finding for the Treatment of Rhinitis/Rhinoconjunctivitis Against Mite Allergy
Official title: Double Blind, Placebo-controlled, Dose Finding, Prospective, Multicenter Clinical Trial for the Treatment of Rhinitis/Rhinoconjunctivitis Against a Mixture of Dermatophagoides Pteronyssinus and Dermatophagoides Farinae Allergen Extract
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rhinitis
Rhinoconjunctivitis
Keywords: Rhinitis / Rhinoconjunctivitis
Vaccine
Immunotherapy
Mite
Allergy
Lead sponsor: Inmunotek S.L.
Sponsor class: INDUSTRY
First posted: 2016-01-25
Enrollment: 186
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: The purpose of the study is to evaluate the more efficient dose for the treatment of rhinitis/rhinoconjunctivitis against mite allergy

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

Eligibility criteria: 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 Dermatophagoides pteronyssinus and/or Dermatophagoides farinae allergy
* Subjects with a positive skin prick-test (wheal sixe \>6 mm diameter)
* Specific immunoglobulin E against house dust mites \>10 kU/L and whose determination does not exceed 6 months prior to the inclusion visit
* Age between 12 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, 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 mites 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 mites allergen extract.
* 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.

Primary outcomes:
measure: Concentration required to elicit a positive response after nasal provocation test (NPT)
timeFrame: 4 months
Secondary outcomes:
measure: Dose finding skin prick test
timeFrame: 4 months
measure: Number of participants with treatment-related adverse events as assessed by MM09-SIT-013
timeFrame: 4 months
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Elche
country: Spain
facility: Hospital Del Vinalopo
state: Alicante
city: Elda
country: Spain
facility: Hospital General Universitario de Elda-Virgen de La Salud
state: Alicante
city: Orihuela
country: Spain
facility: Hospital Vega Baja Orihuela
state: Alicante
city: Castellón de la Plana
country: Spain
facility: Hospital Universitari de Castelló
state: Castellón
city: Vila-real
country: Spain
facility: Hospital de La Plana
state: Castellón
city: Manises
country: Spain
facility: Hospital de Manises
state: Valencia
city: Xátiva
country: Spain
facility: Hospital Lluis Alcanyis de Xátiva
state: Valencia
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Alicante
country: Spain
facility: Hospital Vithas Internacional Medimar
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valencia
country: Spain
facility: HOSPITAL UNIVERSITARI I POLITÈCNIC LA FE Adults
city: Valencia
country: Spain
facility: HOSPITAL UNIVERSITARI I POLITÈCNIC LA FE child
Study officials:
name: Mª Dolores Hernández, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Pilar Alba, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Carmen Pérez, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Javier Montoro, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Antonio de Mateo, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: David El-Qutob, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Javier Fernández, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Vicente Jover, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Isabel Flores, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Mónica Antón, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Carmen Andreu, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Luis Angel Navarro, PhD; MD
role: PRINCIPAL_INVESTIGATOR
name: Ángel Ferrer
role: PRINCIPAL_INVESTIGATOR
name: Antonio Nieto, PhD; MD
role: STUDY_DIRECTOR
References:
citation: Soria I, Lopez-Relano J, Vinuela M, Tudela JI, Angelina A, Benito-Villalvilla C, Diez-Rivero CM, Cases B, Manzano AI, Fernandez-Caldas E, Casanovas M, Palomares O, Subiza JL. Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice. Allergy. 2018 Apr;73(4):875-884. doi: 10.1111/all.13396. Epub 2018 Jan 31.
citation: Manzano AI, Javier Canada F, Cases B, Sirvent S, Soria I, Palomares O, Fernandez-Caldas E, Casanovas M, Jimenez-Barbero J, Subiza JL. Structural studies of novel glycoconjugates from polymerized allergens (allergoids) and mannans as allergy vaccines. Glycoconj J. 2016 Feb;33(1):93-101. doi: 10.1007/s10719-015-9640-4. Epub 2015 Nov 25.
citation: Sirvent S, Soria I, Cirauqui C, Cases B, Manzano AI, Diez-Rivero CM, Reche PA, Lopez-Relano J, Martinez-Naves E, Canada FJ, Jimenez-Barbero J, Subiza J, Casanovas M, Fernandez-Caldas E, Subiza JL, Palomares O. Novel vaccines targeting dendritic cells by coupling allergoids to nonoxidized mannan enhance allergen uptake and induce functional regulatory T cells through programmed death ligand 1. J Allergy Clin Immunol. 2016 Aug;138(2):558-567.e11. doi: 10.1016/j.jaci.2016.02.029. Epub 2016 Apr 13.
citation: Soria I, Alvarez J, Manzano AI, Lopez-Relano J, Cases B, Mas-Fontao A, Canada FJ, Fernandez-Caldas E, Casanovas M, Jimenez-Barbero J, Palomares O, Vinals-Florez LM, Subiza JL. Mite allergoids coupled to nonoxidized mannan from Saccharomyces cerevisae efficiently target canine dendritic cells for novel allergy immunotherapy in veterinary medicine. Vet Immunol Immunopathol. 2017 Aug;190:65-72. doi: 10.1016/j.vetimm.2017.07.004. Epub 2017 Jul 23.