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

NCT ID: NCT05400811

Last Updated: 2022-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-31

Study Completion Date

2025-07-31

Brief Summary

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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.

Detailed Description

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Prospective multicenter randomized double-dummy clinical trial of three active treatment groups compared to one placebo group. The principal objective of the clinical trial is 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.

The primary efficacy endpoint will be the symptom score and medication consumption required for the control of asthma and rhinitis/rhinoconjunctivitis symptoms.

The study design consists of 3 active treatment groups and one placebo group. The trial population will include 400 subjects between the age of 12 and 60 years that will receive the treatment during 12 months.

Conditions

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House Dust Mite Allergy Perennial Allergic Rhinitis Allergic Rhinoconjunctivitis Allergic Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, randomized, placebo-controlled, double-blind, double-dummy, multi-center trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
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.

Study Groups

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

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.

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

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

Placebo sublingual

Intervention Type 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

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.

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

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

Placebo subcutaneous

Intervention Type BIOLOGICAL

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

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

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.

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

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

Placebo subcutaneous

Intervention Type BIOLOGICAL

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

Group IV: Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo subcutaneous

Intervention Type BIOLOGICAL

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

Placebo sublingual

Intervention Type BIOLOGICAL

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

Interventions

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

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

Intervention Type BIOLOGICAL

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

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

Intervention Type BIOLOGICAL

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

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

Intervention Type BIOLOGICAL

Placebo subcutaneous

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

Intervention Type BIOLOGICAL

Placebo sublingual

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Signed and dated Informed Consent Form (ICF).
2. Female or male aged 12 to 60 years, both included.
3. 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.
4. Positive skin prick test (wheal major diameter ≥ 5 mm) to a standardized allergen extract of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae.
5. 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.
6. Women of childbearing age must have a urine pregnancy test negative result before enrolling the study.
7. Women of childbearing age must commit to using an adequate contraception method.
8. Capable of complying with dosage regimen.
9. Owning a smartphone to register symptoms and medication consumption.
10. A negative skin prick test to other aeroallergens with specific IgE \< 3.5 kU/L with no clinical relevance.

Exclusion Criteria

1. 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.
2. Positive skin prick test to other aeroallergens, except for intermittent symptoms due to temporary exposition to dander.
3. Those cases in which AIT would be a contraindication according to the criteria of European Allergy and Clinical Immunology Immunotherapy Subcommittee.
4. Uncontrolled or severe asthma and/or FEV1 \<70% despite pharmacological treatment by the time of enrolment.
5. Intake of β-blockers.
6. Use of immunosuppressive or biological drug.
7. Unstable patients by the time of enrolment (acute exacerbation asthma, respiratory infection, fever, acute pruritus, etc).
8. Patients who have suffered chronic urticaria during the last 2 years, severe anaphylaxis, or family history of angioedema.
9. Having any contraindication for the use of adrenaline (hyperthyroidism, heart disease, high blood pressure).
10. 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.
11. Autoimmune diseases (thyroiditis, lupus, etc.), tumoral diseases or immunodeficiencies.
12. Participants that the investigator believes could not comply with the study protocol or have serious psychiatric disorders.
13. Known allergy to any of the ingredients of the study medication except for mites.
14. Lower respiratory tract diseases different from asthma as bronchiectasis or chronic obstructive pulmonary disease.
15. Breast-feeding or pregnant women.
16. Being immediate family of the investigator.
17. Concurrent participation in other clinical trials or prior participation within 30 days prior to inclusion.
18. History of serious systemic reactions, including food, Hymenoptera venom, medications, etc.
Minimum Eligible Age

12 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BioClever 2005 S.L.

OTHER

Sponsor Role collaborator

NTS hub S.L

UNKNOWN

Sponsor Role collaborator

Inmunotek S.L.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ana Isabel Tabar Purroy, MD. PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital of Navarra

Locations

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Hospital Universitario de Elche

Elche, Alicante, Spain

Site Status

Policlínica Nuestra Sra del Rosario

Ibiza Town, Balearic Islands, Spain

Site Status

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona, Spain

Site Status

Hospital de Terrassa

Terrassa, Barcelona, Spain

Site Status

Hospital Universitario de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital Universitario de Canarias

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

Site Status

Hospital Universitario A Coruña

A Coruña, , Spain

Site Status

Hospital General Universitario de Alicante

Alicante, , Spain

Site Status

Centro Médico Quiron Salud Alicante

Alicante, , Spain

Site Status

Hopital Quirón Salud Málaga

Málaga, , Spain

Site Status

Clinica del Dr.Pérez Estrada Cornejo

Málaga, , Spain

Site Status

Hospital Universitario Regional de Málaga

Málaga, , Spain

Site Status

Clínica RUSADIR

Melilla, , Spain

Site Status

Complexo Hospitalario Universitario de Pontevedra

Pontevedra, , Spain

Site Status

Hospital Univeristario y Politécnico La Fe

Valencia, , Spain

Site Status

Hospital Universitario de la Plana

Vila-real, , Spain

Site Status

Countries

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Spain

Central Contacts

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Miguel Casanovas, MD, PhD

Role: CONTACT

912908942 ext. 0034

Facility Contacts

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Silvia Martínez Blanco, MD, PhD

Role: primary

Adriana Machinena, MD. PhD

Role: primary

Marta Viñas, MD. PhD

Role: primary

Ana Isabel Tabar Purroy, MD. PhD

Role: primary

Inmaculada Sánchez Machin, MD, PhD

Role: primary

Antonio Parra Arrondo, MD, PhD

Role: primary

Luis Moral, MD, PhD

Role: primary

Angel Ferrer, MD, PhD

Role: primary

Leticia Herrero Lifona, MD, PhD

Role: primary

Manuel Pérez Estrada Cornejo, MD. PhD

Role: primary

Carmén Rondón, MD, PhD

Role: primary

Oliver Alexis Muñoz Daga, MD, PhD

Role: primary

Francisco David El-Qutob López, MD. PhD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 30546997 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27177779 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26603537 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29319882 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28778325 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30183126 (View on PubMed)

Other Identifiers

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MM09-SIT-040

Identifier Type: -

Identifier Source: org_study_id

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