Efficacy and Safety Evaluation for the Treatment of Allergy Against Mites

Rhinoconjunctivitis Clinical Trial

— MM09-SIT-023  

Official title:

Randomized, Double-blinded, Placebo-controlled, Prospective, Multicenter Trial to Evaluate the Efficacy and Safety of SIC in Subjects With Mild/Moderate Asthma and Rhinitis/Rhinoconjunctivitis Sensitized to D.Pteronyssinus and/or D. Farinae

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04435990
• Other study ID #: MM09-SIT-023
• Secondary ID: 2018-004262-34
• Status: Recruiting
• Phase: Phase 3
• Start date: October 6, 2020
• Est. completion date: December 2025

Study information

• Verified date: November 2022
• Source: Inmunotek S.L.
• Contact: Francisco Moreno, MD
• Phone: 956292100
• Email: dr.moreno[@]drlobaton.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A double-blinded, placebo-controlled, prospective, multicenter randomized of 2 active treatment groups, compared to 1 placebo group, for the determination of the efficacy and safety of subcutaneous immunotherapy in patients with rhinitis/rhinoconjunctivitis with mild to moderate asthma, sensitised to Dermatophagoides pteronyssinus and /or Dermatophagoides farinae.

Description:

Double blind, multicenter, parallel placebo controlled study. It includes 150 subjects sensitised to mites, from 14 to 65 years of age. Medication treatment of 1 year. The main outcome: CSMS

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2025
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

Inclusion Criteria:

• Written informed consent.
• Age between 14 and 65, both genders.
• Positive suggestive clinical history of controlled intermittent or persistent asthma with intermittent or persistent moderate to severe rhinitis /rhinoconjunctivitis, due to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The diagnosis of asthma will be valid from 12 months prior to signing the informed consent form
• Subjects with a positive skin prick-test wheal size >5 mm higher diameter due to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The positive and negative control of the test should give consistent results
• Specific immunoglobulin E against house dust mites >3,5 KU/mL (InmunoCAP® o Immulite), for the complete extract of Dermatophagoides pteronyssinus and / or for Dermatophagoides farinae or for some of the molecular components of these allergenic sources
• Subjects should preferably be monosensitized to the study allergens. In case of subjects sensitized to other aeroallergens, only those with the following

characteristics may be included in the study:

• Subjects with positive skin test to Blomia tropicalis and Lepidoglyphus destructor, whose specific IgE values do not exceed or equal the values for the study allergens. The maximum specific IgE value for these allergens is 3.5 KU/L.
• Subjects with positive skin tests to epithelia, as long as they present occasional exposure and symptomatology.
• Subjects with positive skin tests to pollens, whose specific IgE values do not exceed or equal the values of the allergens in the study and who do not present exacerbations during the pollen season. The maximum value of specific IgE for these allergens is 17.5 KU/L.
• Women of childbearing age (from menarche) must present a urine pregnancy test with a negative result at the time of joining the trial, before the first administration of the IMP.
• Women of childbearing age participating in the trial must agree to use an appropriate method of contraception, meaning any act, device, or medication to prevent conception or viable pregnancy, during the trial if they are sexually active.
• Subjects with a diagnosis of asthma according to the GEMA 5.0 guideline.
• Subjects capable of complying with the dosing regimen.
• Subjects who own an smartphone for symptom registration and medication

Exclusion Criteria:

• Subjects with positive prick test to fungus, whose specific IgE is <0,35 KU/L
• Subjects with positive prick test to epiteliums, whose specific IgE is <0,35 KU/L
• Subjects who have received prior immunotherapy in the preceding 5 years for any of the epiteliums, fungus and dust mites.
• Subjects in which immunotherapy may be subject to an absolute general contraindication according to the criteria of the Immunotherapy Committee of the Spanish Society of Allergy and Clinical Immunology and the European Allergy and Clinical Immunology Immunotherapy Subcommittee.
• Subjects with severe or uncontrolled intermittent or persistent asthma, with an FEV1 <70% with respect to the reference value despite adequate pharmacological treatment at the time of inclusion in the trial. Likewise, subjects with intermittent or persistent rhinitis / rhinoconjunctivitis with severe symptoms in which the suspension of oral or systemic antihistamine treatment is contraindicated.
• Subjects who have previously presented a serious secondary reaction during the performance of diagnostic skin tests using the prick test.
• Subjects under treatment with ß-blockers.
• Clinically unstable subjects at the time of inclusion in the trial (acute asthma exacerbation, respiratory infection, feverish process, acute urticaria, etc.).
• Subjects with active chronic urticaria, severe dermography, severe atopic dermatitis, sunburn, active psoriasis with lesions in areas where skin tests are performed, or a history of hereditary angioedema.
• Subjects that have some pathology in which the administration of adrenaline is contraindicated (hyperthyroidism, hypertension, heart disease, etc.).
• Subjects with some other disease not related to moderate rhinoconjunctivitis or asthma, but of potential severity and that may interfere with treatment and follow-up (epilepsy, psychomotor disorder, uncontrolled diabetes, malformations, multiple operations, kidney disease,).
• Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumor diseases or with a diagnosis of immunodeficiencies.
• Subject whose status prevents him from offering cooperation and or who has severe psychiatric disorders.
• Subjects with a known allergy to other components of the investigational medicinal product other than the allergen.
• Subjects with diseases of the lower respiratory tract other than asthma such as emphysema or bronchiectasis.
• Direct investigator's relatives.
• Pregnant women or breastfeeding women.

Related Conditions & MeSH terms

• Asthma
• Asthma, Allergic
• Conjunctivitis
• Rhinitis
• Rhinitis, Allergic
• Rhinoconjunctivitis

Intervention

Biological:
• 10,000 MM09
Purified allergenic extract, and adsorbed in aluminum hydroxide and polymerized with glutaraldehyde, mite mixture (Dermatophagoides pteronyssinus and Dermatophagoides farinae) with a concentration of 10,000 UT / mL
• 30,000 MM09
Purified allergenic extract, and adsorbed in aluminum hydroxide and polymerized with glutaraldehyde, mite mixture (Dermatophagoides pteronyssinus and Dermatophagoides farinae). The concentration is 30,000 UT / mL
• Placebo subcutaneous
The same solution and presentation as the active treatment, but without active ingredients.

Locations

Country	Name	City	State
Spain	Clinica Virgen del Rosario	Algeciras	Cadiz
Spain	Clínica Dermatológica y Alergia	Badajoz
Spain	Hospital de Zafra	Badajoz
Spain	Allergocenter	Barcelona
Spain	Cenvi Medic	Barcelona
Spain	Clínica Corachan	Barcelona
Spain	Hospital Universitari Dexeus	Barcelona	Cataluña
Spain	Clinica privada	Bilbao
Spain	Centro Médico ASISA Dr. Lobatón	Cadiz
Spain	Centro Médico Puerto	Cadiz
Spain	Hospital Quiron Salud Córdoba	Córdoba
Spain	IMED Elche	Elche	Alicante
Spain	Hospital HLA Jerez Puerta Sur	Jerez De La Frontera
Spain	Hospital Polusa	Lugo
Spain	Clinica privada	Málaga
Spain	Alergocantabria	Santander
Spain	Clinica IMED	Valencia
Spain	Hospital Rivera Povisa	Vigo

Sponsors (2)

Lead Sponsor	Collaborator
Inmunotek S.L.	BioClever 2005 S.L.

Country where clinical trial is conducted

Spain, 

References & Publications (5)

Bousquet J, Hejjaoui A, Clauzel AM, Guérin B, Dhivert H, Skassa-Brociek W, Michel FB. Specific immunotherapy with a standardized Dermatophagoides pteronyssinus extract. II. Prediction of efficacy of immunotherapy. J Allergy Clin Immunol. 1988 Dec;82(6):971-7. — View Citation

Branco Ferreira M, Spínola Santos A, Pereira Santos MC, Palma Carlos ML, Pereira Barbosa MA, Palma Carlos AG. Efficacy and safety of specific immunotherapy with a modified mite extract. Allergol Immunopathol (Madr). 2005 Mar-Apr;33(2):80-5. — View Citation

Cardona R, Lopez E, Beltrán J, Sánchez J. Safety of immunotherapy in patients with rhinitis, asthma or atopic dermatitis using an ultra-rush buildup. A retrospective study. Allergol Immunopathol (Madr). 2014 Mar-Apr;42(2):90-5. doi: 10.1016/j.aller.2012.07.005. Epub 2012 Dec 20. — View Citation

Piacentini GL, Vicentini L, Mazzi P, Chilosi M, Martinati L, Boner AL. Mite-antigen avoidance can reduce bronchial epithelial shedding in allergic asthmatic children. Clin Exp Allergy. 1998 May;28(5):561-7. — View Citation

Yepes-Núñez JJ, Gómez C, Espinoza Y, Cardona R. [The impact of subcutaneous immunotherapy with Dermatophagoides farinae and Dermatophagoides pteronyssinus on the quality of life of patients with allergic rhinitis and asthma]. Biomedica. 2014 Apr-Jun;34(2):282-90. doi: 10.1590/S0120-41572014000200014. Spanish. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CSMS: Combined Symptoms and Medication Score	Evaluation of the number of symptoms and the consumption of medication necessary for the control of such symptoms in asthma and rhinitis / rhinoconjunctivitis of each subject during the trial, of the groups with each other and with respect to placebo.	12 months
Secondary	Medication-free days	Number of days that the subjects need no medication	12 months
Secondary	Symptom-free days	Number of days that the subjects have no symptom	12 months
Secondary	Number of participants with treatment-related adverse events as assessed by MM09-SIT-023	Comparison between the beginning and end of the trial and among active groups and placebo	12 months
Secondary	Quality of life associated with asthma	The quality of life associated with asthma will be measured following the GINA questionnaire.; The GINA questionnaire consists of 4 questions. In questions 1-4, patients recall their experience during the last 4 weeks and answer using YES or NO.; The interpretation of the answers is as follows: Well-controlled: None of the answers are YES Partly controlled: 1 - 2 answers are YES Uncontrolled: 3-4 answers are YES	12 months
Secondary	Quality of life associated with rhinitis	The quality of life associated with rhinitis will be measured following the test ESPRINT-15.; The scoring of the questionnaire will be carried out as follows: The global sum of the scores (ranging from "0 = nothing has bothered me" to "6 = it has bothered me a lot") of the 14 items plus the score given in the general questionnaire (ranging from "0 = Excellent" to "4 = Bad"). This sum is divided by the total number of items (15 items).; The interpretation of the scores is between 0 (low impact) and 6 (high impact).	12 months
Secondary	Visual Analogue Scale (VAS)	Visual Analogue Scale in which the subject has to indicate how he/she feels regarding to his allergy symptoms at the moment from 1 to 10. Being 1 very bad and 10 very well.	12 months
Secondary	Immunological parameters	Analyses of total Ig3 and specific IgA,IgG and IgG4	12 months