Dose Finding for the Treatment of Rhinitis/Rhinoconjunctivitis Against Mite Allergy

Rhinitis Clinical Trial

— MM09  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02661854
• Other study ID #: MM09-SIT-013
• Secondary ID: 2015-000820-27
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 21, 2016
• Est. completion date: July 2020

Study information

• Verified date: March 2020
• Source: Inmunotek S.L.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 186
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Conjunctivitis
• Rhinitis
• Rhinoconjunctivitis

Intervention

Biological:
• MM09 Mannosylated 5.000 subcutaneous
Mixture of the following mites: Dermatophagoides pteronyssinus and Dermatophagoides farinae, allergen extract with a concentration of 5.000 MTU (Mannosylated Therapeutic Units)/ml subcutaneous
• MM09 Mannosylated 10.000 subcutaneous
Mixture of the following mites: Dermatophagoides pteronyssinus and Dermatophagoides farinae, allergen extract with a concentration of 10.000 MTU (Mannosylated Therapeutic Units)/ml subcutaneous
• MM09 Mannosylated 30.000 subcutaneous
Mixture of the following mites: Dermatophagoides pteronyssinus and Dermatophagoides farinae, allergen extract with a concentration of 30.000 MTU (Mannosylated Therapeutic Units)/ml subcutaneous
• MM09 Mannosylated 50.000 subcutaneous
Mixture of the following mites: Dermatophagoides pteronyssinus and Dermatophagoides farinae, allergen extract with a concentration of 50.000 MTU (Mannosylated Therapeutic Units)/ml subcutaneous
• MM09 Mannosylated 5.000 sublingual
Mixture of the following mites: Dermatophagoides pteronyssinus and Dermatophagoides farinae, allergen extract with a concentration of 5.000 MTU (Mannosylated Therapeutic Units)/ml sublingual
• MM09 Mannosylated 10.000 sublingual
Mixture of the following mites: Dermatophagoides pteronyssinus and Dermatophagoides farinae, allergen extract with a concentration of 10.000 MTU (Mannosylated Therapeutic Units)/ml sublingual
• MM09 Mannosylated 30.000 sublingual
Mixture of the following mites: Dermatophagoides pteronyssinus and Dermatophagoides farinae, allergen extract with a concentration of 30.000 MTU (Mannosylated Therapeutic Units)/ml sublingual
• MM09 Mannosylated 50.000 sublingual
Mixture of the following mites: Dermatophagoides pteronyssinus and Dermatophagoides farinae, allergen extract with a concentration of 50.000 MTU (Mannosylated Therapeutic Units)/ml sublingual
• Subcutaneous placebo
Comparison between placebo and active group
• Sublingual placebo
Comparison between placebo and active group

Locations

Country	Name	City	State
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Vithas Internacional Medimar	Alicante
Spain	Hospital Universitari de Castelló	Castellón de la Plana	Castellón
Spain	Hospital Del Vinalopo	Elche	Alicante
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital General Universitario de Elda-Virgen de La Salud	Elda	Alicante
Spain	Hospital de Manises	Manises	Valencia
Spain	Hospital Vega Baja Orihuela	Orihuela	Alicante
Spain	Hospital Arnau de Vilanova	Valencia
Spain	HOSPITAL UNIVERSITARI I POLITÈCNIC LA FE Adults	Valencia
Spain	HOSPITAL UNIVERSITARI I POLITÈCNIC LA FE child	Valencia
Spain	Hospital Universitario Doctor Peset	Valencia
Spain	Hospital de La Plana	Vila-real	Castellón
Spain	Hospital Lluis Alcanyis de Xátiva	Xátiva	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Inmunotek S.L.

Country where clinical trial is conducted

Spain, 

References & Publications (4)

Manzano AI, Javier Cañada F, Cases B, Sirvent S, Soria I, Palomares O, Fernández-Caldas E, Casanovas M, Jiménez-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. — View Citation

Sirvent S, Soria I, Cirauqui C, Cases B, Manzano AI, Diez-Rivero CM, Reche PA, López-Relaño J, Martínez-Naves E, Cañada FJ, Jiménez-Barbero J, Subiza J, Casanovas M, Fernández-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. — View Citation

Soria I, Alvarez J, Manzano AI, López-Relaño J, Cases B, Mas-Fontao A, Cañada FJ, Fernández-Caldas E, Casanovas M, Jiménez-Barbero J, Palomares O, Viñals-Flórez 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. — View Citation

Soria I, López-Relaño J, Viñuela M, Tudela JI, Angelina A, Benito-Villalvilla C, Díez-Rivero CM, Cases B, Manzano AI, Fernández-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration required to elicit a positive response after nasal provocation test (NPT)	Change in the threshold concentration of mite 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	Dose finding skin prick test	Comparison between the beginning and end of the trial and among active groups and placebo	4 months
Secondary	Number of participants with treatment-related adverse events as assessed by MM09-SIT-013	Comparison between the beginning and end of the trial and among active groups and placebo	4 months