Efficacy and Safety Evaluation for the Treatment of Allergy Against Mites (MM09-SIT-023)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Rhinitis, Allergic; Rhinoconjunctivitis; Asthma, Allergic
• Intervention / Treatment: Biological: 10,000 MM09; Biological: 30,000 MM09; Biological: Placebo subcutaneous

Detailed 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

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Francisco Moreno, MD; Phone Number: +34 956292100; Email: dr.moreno@drlobaton.org
• Study Contact Backup: Name: Miguel Casanovas, MD PhD; Phone Number: +34 916510010; Email: mcasanovas@inmunotek.com

Study Locations

• Spain
  • Badajoz, Spain
    • Recruiting
    • Clinica Dermatologica Y Alergia
    • Principal Investigator: Irán Sánchez, DM
  • Badajoz, Spain
    • Not yet recruiting
    • Hospital de Zafra
    • Principal Investigator: Silvia Sánchez, DM
  • Barcelona, Spain
    • Active, not recruiting
    • Allergocenter
  • Barcelona, Spain
    • Active, not recruiting
    • Cenvi Medic
  • Barcelona, Spain
    • Recruiting
    • Clinica Corachan
    • Principal Investigator: César Alías, DM
  • Bilbao, Spain
    • Active, not recruiting
    • Clinica privada
  • Cadiz, Spain
    • Recruiting
    • Centro Médico ASISA Dr. Lobatón
    • Principal Investigator: Francisco Moreno, DM
  • Cadiz, Spain
    • Active, not recruiting
    • Centro Médico Puerto
  • Córdoba, Spain
    • Recruiting
    • Hospital Quiron Salud Córdoba
    • Principal Investigator: Ignacio Garcia Núñez, DM
  • Jerez De La Frontera, Spain
    • Active, not recruiting
    • Hospital HLA Jerez Puerta Sur
  • Lugo, Spain
    • Recruiting
    • Hospital Polusa
    • Principal Investigator: Joaquín Martín, DM
  • Málaga, Spain
    • Recruiting
    • Clinica privada
    • Principal Investigator: Manuel Barceló Muñoz, DM
  • Santander, Spain
    • Active, not recruiting
    • Alergocantabria
  • Valencia, Spain
    • Active, not recruiting
    • Clinica iMED
  • Vigo, Spain
    • Not yet recruiting
    • Hospital Rivera Povisa
    • Principal Investigator: Carmen Mogío, DM
  • Alicante
    • Elche, Alicante, Spain
      • Recruiting
      • IMED Elche
      • Principal Investigator: Eugenia Margarita Campos, DM
  • Cadiz
    • Algeciras, Cadiz, Spain
      • Active, not recruiting
      • Clinica Virgen del Rosario
  • Cataluña
    • Barcelona, Cataluña, Spain, 08028
      • Recruiting
      • Hospital Universitari Dexeus
      • Contact: Elena Botey, DM
      • Sub-Investigator: Begoña Navarro, DM

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.
• 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 β-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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental:10,000 MM09; 10,000 TU/mL of subcutaneous immunotherapy	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
Experimental: Experimental: 30,000 MM09; 30,000 TU/mL of subcutaneous immunotherapy	Biological: 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 Comparator: Placebo subcutaneous; The same solution and presentation as the active treatment, but without any active ingredients.	Biological: Placebo subcutaneous; The same solution and presentation as the active treatment, but without active ingredients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication-free days	Number of days that the subjects need no medication	12 months
Symptom-free days	Number of days that the subjects have no symptom	12 months
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
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
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
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
Immunological parameters	Analyses of total Ig3 and specific IgA,IgG and IgG4	12 months

Collaborators and Investigators

• Sponsor: Inmunotek S.L.
• Collaborators: BioClever 2005 S.L.
• Investigators: Principal Investigator: Daniel Pujadas, MD, Quirón Palma de Mallorca; Principal Investigator: Mario Tubella, MD, Cenvi Medic, Barcelona; Principal Investigator: Alfonso Malet, MD, Allergocentre, Barcelona; Principal Investigator: Miguel Ángel Añó, MD, Alergocantabria, Santander; Principal Investigator: Miguel Herrías, MD, Clinica Privada Bilbao; Principal Investigator: Antonio Letrán, MD, Hospital HLA Jeréz Puerta del Sur; Principal Investigator: Diego Gutiérrez, MD, Clínica Virgen del Rosario, Algeciras; Principal Investigator: Ignacio Garcia, MD, Clinica Quirón Salud, Córdoba; Principal Investigator: Manuel Barceló, MD, Clinica Privada, Málaga.; Principal Investigator: Mº José Pereira, MD, Centro Médico Puerto, Jerez; Principal Investigator: Isabella Raducán, MD, Clínica TECMA, Alzira; Principal Investigator: Noelia Colomer, MD, Clínica IMED, Valencia; Principal Investigator: Eugenia Margarita Campos, MD, Clínica IMED, Elche; Principal Investigator: César Alías, MD, Clínica Corachan, Barcelona; Principal Investigator: Joaquín Martín, MD, Hospital POLUSA, Lugo

Publications and helpful links

General Publications

• 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. doi: 10.1046/j.1365-2222.1998.00260.x.
• Yepes-Nunez JJ, Gomez 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.
• Cardona R, Lopez E, Beltran J, Sanchez 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.
• Bousquet J, Hejjaoui A, Clauzel AM, Guerin 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. doi: 10.1016/0091-6749(88)90133-9.
• Branco Ferreira M, Spinola 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. doi: 10.1157/13072918.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2020
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 21, 2022
• Last Update Submitted That Met QC Criteria: November 18, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Allergy; Immunotherapy; Mites; Rhinitis/ Rhinoconjunctivitis; Mild to moderate asthma
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Eye Diseases; Bronchial Diseases; Otorhinolaryngologic Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Conjunctival Diseases; Asthma; Rhinitis; Rhinitis, Allergic; Conjunctivitis
• Other Study ID Numbers: MM09-SIT-023; 2018-004262-34 (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