Efficacy and Safety Evaluation for the Treatment of HDM Induced Allergic Asthma and Rhinitis/Rhinoconjunctivitis

NCT05400811 | Unknown Phase 3

• 1 other identifier: MM09-SIT-040
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 16

Brief Summary

Prospective, randomized, placebo-controlled, multicenter of 3 active treatment groups, compared to 1 placebo group, for the determination of the efficacy and safety of subcutaneous immunotherapy in patients with mild to moderate asthma and rhinitis/rhinoconjunctivitis (intermittent or persistent) allergic to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae.

Conditions

House Dust Mite Allergy; Perennial Allergic Rhinitis; Allergic Rhinoconjunctivitis; Allergic Asthma

Keywords

Rhinitis/ Rhinoconjunctivitis; Allergy; Immunotherapy; Mild to moderate asthma

Outcome Measures

Primary Outcomes (1)

• 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. \- The endpoint for each asthma and rhinitis / rhinoconjunctivitis symptom will be as follows: 0 = No symptoms; 1 = Mild; 2 = Moderate; 3 = Severe Total daily symptom score = 0-3 The asthma medication will be scored based on the therapeutic step in which drugs are included in the GEMA 5 guide. The rhinitis / rhinoconjunctivitis medication score: 0 = No medication; 1 = oral or topical (eyes or nose) non-sedative H1 antihistamines (H1A); 2 = intranasal corticosteroids (INS) with / without H1A; 3 = oral corticosteroids with/without (INS), with/without H1A Total daily medication score = 0-3

  12 months

Secondary Outcomes (17)

• Asthma symptom-free days

  12 months

• Rhinitis / rhinoconjunctivitis symptom-free days

  12 months

• Asthma medication-free days

  12 months

• Rhinitis / rhinoconjunctivitis medication-free days

  12 months

• Respiratory function_FEV1

  Baseline, month 6, month 12

Study Arms (4)

Group I: MM09 allergoid-mannan conjugates SC (3.000 UTm/mL) + sublingual placebo

EXPERIMENTAL

Mixture of allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae conjugated to mannan at 3,000 UTm/mL subcutaneous immunotherapy + sublingual placebo. Subcutaneous active treatment will be administered once a month for 12 months. Sublingual placebo will be administered daily (2 subsequent administrations) for 12 months.

Biological: MM09 allergoid-mannan conjugates subcutaneous (3.000 UTm/mL); Biological: Placebo sublingual

Group II: MM09 allergoid-mannan conjugates SL (3.000 UTm/mL) + subcutaneous placebo

EXPERIMENTAL

Mixture of allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae conjugated to mannan sublingual immunotherapy at 3.000 UTm/mL + subcutaneous placebo. Sublingual active treatment will be administered daily (2 subsequent administrations) for 12 months. Subcutaneous placebo will be administered once a month for 12 months.

Biological: MM09 allergoid-mannan conjugates Sublingual (3.000 UTm/mL); Biological: Placebo subcutaneous

Group III: MM09 allergoid-mannan conjugates SL (9.000 UTm/mL) + subcutaneous placebo

EXPERIMENTAL

Mixture of allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae conjugated to mannan sublingual immunotherapy at 9.000 UTm/mL + subcutaneous placebo. Sublingual active treatment will be administered daily (2 subsequent administrations) for 12 months. Subcutaneous placebo will be administered once a month for 12 months.

Biological: MM09 allergoid-mannan conjugates Sublingual (9.000 UTm/mL); Biological: Placebo subcutaneous

Group IV: Placebo

PLACEBO COMPARATOR

Mixture of sublingual placebo + subcutaneous placebo. Sublingual placebo will be administered daily (2 subsequent administrations) for 12 months. Subcutaneous placebo will be administered once a month for 12 months

Biological: Placebo subcutaneous; Biological: Placebo sublingual

Interventions

MM09 allergoid-mannan conjugates subcutaneous (3.000 UTm/mL) BIOLOGICAL

Mixture of allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae conjugated to mannan at 3.000 UTm/mL for subcutaneous administration.

Group I: MM09 allergoid-mannan conjugates SC (3.000 UTm/mL) + sublingual placebo

MM09 allergoid-mannan conjugates Sublingual (3.000 UTm/mL) BIOLOGICAL

Mixture of allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae conjugated to mannan at 3.000 UTm/mL for sublingual administration.

Group II: MM09 allergoid-mannan conjugates SL (3.000 UTm/mL) + subcutaneous placebo

MM09 allergoid-mannan conjugates Sublingual (9.000 UTm/mL) BIOLOGICAL

Mixture of allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae conjugated to mannan at 9.000 UTm/mL for sublingual administration.

Group III: MM09 allergoid-mannan conjugates SL (9.000 UTm/mL) + subcutaneous placebo

Placebo subcutaneous BIOLOGICAL

The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.

Group II: MM09 allergoid-mannan conjugates SL (3.000 UTm/mL) + subcutaneous placebo; Group III: MM09 allergoid-mannan conjugates SL (9.000 UTm/mL) + subcutaneous placebo; Group IV: Placebo

Placebo sublingual BIOLOGICAL

The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.

Group I: MM09 allergoid-mannan conjugates SC (3.000 UTm/mL) + sublingual placebo; Group IV: Placebo

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed and dated Informed Consent Form (ICF).
• Female or male aged 12 to 60 years, both included.
• Confirmed clinical history of inhalation allergy (mild-moderate controlled intermittent or persistent asthma according to the definition of GEMA 5.0 and GINA 2020 and intermittent or persistent rhinitis / rhinoconjunctivitis according to the ARIA classification, caused by Dermatophagoides pteronyssinus and / or Dermatophagoides farinae). The asthma diagnosis will be valid up to 24 months prior to signing the informed consent.
• Positive skin prick test (wheal major diameter ≥ 5 mm) to a standardized allergen extract of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae.
• Specific IgE against a complete extract of D. pteronyssinus and/or D. farinae or any of the molecular components of allergenic sources with a value ≥ 3.5 kU/L.
• Women of childbearing age must have a urine pregnancy test negative result before enrolling the study.
• Women of childbearing age must commit to using an adequate contraception method.
• Capable of complying with dosage regimen.
• Owning a smartphone to register symptoms and medication consumption.
• A negative skin prick test to other aeroallergens with specific IgE \< 3.5 kU/L with no clinical relevance.

You may not qualify if:

• Previous immunotherapy to any of the tested allergen during the last 5 years or any desensitization process in the last 2 years (ITO, milk, egg, ...) or currently receiving immunotherapy with any other allergen.
• Positive skin prick test to other aeroallergens, except for intermittent symptoms due to temporary exposition to dander.
• Those cases in which AIT would be a contraindication according to the criteria of European Allergy and Clinical Immunology Immunotherapy Subcommittee.
• Uncontrolled or severe asthma and/or FEV1 \<70% despite pharmacological treatment by the time of enrolment.
• Intake of β-blockers.
• Use of immunosuppressive or biological drug.
• Unstable patients by the time of enrolment (acute exacerbation asthma, respiratory infection, fever, acute pruritus, etc).
• Patients who have suffered chronic urticaria during the last 2 years, severe anaphylaxis, or family history of angioedema.
• Having any contraindication for the use of adrenaline (hyperthyroidism, heart disease, high blood pressure).
• Other severe diseases not related to allergic asthma or rhinitis that could interfere in the study treatment or the follow-up (epilepsy, psychomotor agitation, diabetes, malformations, nephropathy) according to medical criteria.
• Autoimmune diseases (thyroiditis, lupus, etc.), tumoral diseases or immunodeficiencies.
• Participants that the investigator believes could not comply with the study protocol or have serious psychiatric disorders.
• Known allergy to any of the ingredients of the study medication except for mites.
• Lower respiratory tract diseases different from asthma as bronchiectasis or chronic obstructive pulmonary disease.
• Breast-feeding or pregnant women.

Sponsors & Collaborators

• Inmunotek S.L.: lead
• BioClever 2005 S.L.: collaborator
• NTS hub S.L: collaborator

Study Sites (16)

Hospital Universitario de Elche

Elche, Alicante, 03203, Spain

Location

Policlínica Nuestra Sra del Rosario

Ibiza Town, Balearic Islands, 07800, Spain

Location

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Hospital de Terrassa

Terrassa, Barcelona, 08227, Spain

Location

Hospital Universitario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Hospital Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Centro Médico Quiron Salud Alicante

Alicante, 03015, Spain

Location

Hopital Quirón Salud Málaga

Málaga, 29004, Spain

Location

Clinica del Dr.Pérez Estrada Cornejo

Málaga, 29005, Spain

Location

Hospital Universitario Regional de Málaga

Málaga, 29010, Spain

Location

Clínica RUSADIR

Melilla, 52006, Spain

Location

Complexo Hospitalario Universitario de Pontevedra

Pontevedra, 36071, Spain

Location

Hospital Univeristario y Politécnico La Fe

Valencia, 46026, Spain

Location

Hospital Universitario de la Plana

Vila-real, 12540, Spain

Location

Related Publications (6)

• Benito-Villalvilla C, Soria I, Subiza JL, Palomares O. Novel vaccines targeting dendritic cells by coupling allergoids to mannan. Allergo J Int. 2018;27(8):256-262. doi: 10.1007/s40629-018-0069-8. Epub 2018 May 18.

  PMID: 30546997 BACKGROUND

• 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.

  PMID: 27177779 BACKGROUND

• 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.

  PMID: 26603537 BACKGROUND

• 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.

  PMID: 29319882 BACKGROUND

• 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.

  PMID: 28778325 BACKGROUND

• Gonzalez JL, Zalve V, Fernandez-Caldas E, Cases B, Subiza JL, Casanovas M. A pilot study of immunotherapy in dogs with atopic dermatitis using a mannan-Dermatophagoides farinae allergoid targeting dendritic cells. Vet Dermatol. 2018 Oct;29(5):449-e152. doi: 10.1111/vde.12679.

  PMID: 30183126 BACKGROUND

MeSH Terms

Conditions

Dust Mite Allergy; Rhinitis, Allergic, Perennial; Hypersensitivity

Condition Hierarchy (Ancestors)

Rhinitis, Allergic; Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Immune System Diseases

Study Officials

• Ana Isabel Tabar Purroy, MD. PhD

  Hospital of Navarra

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miguel Casanovas, MD, PhD

CONTACT

912908942; mcasanovas@inmunotek.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the trial, both the investigator and the included subjects will be unaware of the treatment each subject is receiving. The person in charge of data analysis will also not know the treatment assigned to each subject until the database has been closed. Neither the subject nor the investigator knows what treatment each subject is receiving, all the trial medication is identical in terms of outer packaging and appearance.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, placebo-controlled, double-blind, double-dummy, multi-center trial

Study Record Dates

• First Submitted: May 27, 2022
• First Posted: June 2, 2022
• Study Start: December 1, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2025
• Last Updated: November 18, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (16)