Clinical Trial to Evaluate the Efficacy and Safety of Polymerized, Mannan-Conjugated Dermatophagoides Allergen Extract

NCT05641272 | Not Yet Recruiting Phase 2

• 1 other identifier: MM09-SLG-056
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of polymerized and mannan conjugated allergen extract of Dermatophagoides for the treatment of allergic rhinitis/rhinoconjunctivitis with or without asthma. The main objective of the clinical trial is to evaluate the clinical efficacy of the investigational medicinal product, administered sublingually, compared to placebo for the treatment of moderate-severe rhinitis/rhinoconjunctivitis with or without mild to moderate asthma and controlled using the Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (R-CSMS).

Conditions

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

Keywords

Allergy; Mites; Hypersensitivity; Rhinitis; Rhinoconjunctivitis

Outcome Measures

Primary Outcomes (1)

• Rhinitis/rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS)

  Assessment of the number of rhinitis/rhinoconjunctivitis symptoms and medication consumption required to control these symptoms for each subject during the trial, for each group compared to the others, and compared to placebo. Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score will be based on the work done by Pfaar et al. The score for each rhinitis/rhinoconjunctivitis symptom will be 0 = No symptoms; 1 = Mild; 2 = Moderate; 3 = Severe. Total daily symptom score = 0-3 The score for Rhinitis/rhinoconjunctivitis medication will be: 0 = No medication; 1 = Oral or topical (eye or nose) non-sedating 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

  6 months

Secondary Outcomes (28)

• Rhinitis/ Rhinoconjunctivitis Symptom Score (RSS)

  6 months

• Rhinitis/Rhinoconjunctivitis Medication Score (RMS)

  6 months

• Asthma Combined Symptom and Medication Score (ACSMS)

  6 months

• Asthma Symptom Score (ASS)

  6 months

• Asthma Medication Score (AMS)

  6 months

Study Arms (3)

Group I: sublingual allergoid-mannan conjugates (MM09 at 3.000 UTm/mL)

EXPERIMENTAL

Allergoid (Dermatophagoides pteronyssinus and Dermatophagoides farinae)-mannan conjugates (MM09) at 3.000 UTm/mL for sublingual immunotherapy. The dose is 2 sprays daily applied to the sublingual mucosa for 6 months.

Biological: 3,000 MM09

Group II: sublingual allergoid-mannan conjugates (MM09 at 9.000 UTm/mL)

EXPERIMENTAL

Allergoid (Dermatophagoides pteronyssinus and Dermatophagoides farinae)-mannan conjugates (MM09) at 9.000 UTm/mL for sublingual immunotherapy.. The dose is 2 sprays daily applied to the sublingual mucosa for 6 months.

Biological: 9,000 MM09

Group III: sublingual placebo

PLACEBO COMPARATOR

The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.The dose is 2 sprays daily applied to the sublingual mucosa for 6 months.

Other: Placebo sublingual

Interventions

3,000 MM09 BIOLOGICAL

Allergoid (Dermatophagoides pteronyssinus and Dermatophagoides farinae)-mannan conjugates (MM09) at 3.000 UTm/mL for sublingual immunotherapy.

Group I: sublingual allergoid-mannan conjugates (MM09 at 3.000 UTm/mL)

9,000 MM09 BIOLOGICAL

Allergoid (Dermatophagoides pteronyssinus and Dermatophagoides farinae)-mannan conjugates (MM09) at 9.000 UTm/mL for sublingual immunotherapy.

Group II: sublingual allergoid-mannan conjugates (MM09 at 9.000 UTm/mL)

Placebo sublingual OTHER

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

Group III: sublingual 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 Informed Consent Form.
• Male or female, aged between 12 and 60 years, both included.
• Confirmed clinical history of inhalation allergy with moderate-severe rhinitis/rhinoconjunctivitis according to the ARIA classification with or without controlled mild-moderate intermittent or persistent asthma according to the definition of GEMA 5.0 y GINA caused by allergy to mites (D. pteronyssinus and/or D. farinae). The asthma diagnostic will be valid up to 24 months prior to signing the informed consent form.
• Combined Symptom and Medication Score for moderate to severe rhinitis/rhinoconjunctivitis (RCSMS) ≥ 1,8 out of 3.
• Positive skin prick test (wheal major diameter ≥ 5 mm) to a standardized allergen extract of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The results will be valid up to 12 months prior to signing the informed consent form.
• Specific IgE against a complete extract of Dermatophagoides pteronyssinus and/or D. farinae or any the molecular components of allergenic sources with a value ≥ 3.5 kU/L. The results will be valid up to 12 months prior to signing the informed consent form.
• Subjects shall preferably be monosensitised to the study allergens. In case of subjects sensitised to other aeroallergens, only those with the following characteristics may be included in the study (results will be valid up to 12 months prior to signing the informed consent form):
• Subjects with a positive skin prick test to Blomia tropicalis and Lepidoglyphus destructor, whose wheal major diameter and specific IgE values do not exceed or equal the values for the study allergens.
• Subjects with a positive skin prick test for dander if they have occasional exposure and symptoms.
• Subjects with positive skin prick test to pollens, whose specific IgE values do not exceed or equal the values for the study allergens and who also do not have exacerbations during pollen season. The maximum specific IgE value to theses allergens is 17.5 kU/L.
• Subjects with negative skin prick test to mold. In case specific IgE determination have been performed, the result must be \<0.35 kU/L.
• Women of childbearing age (since menarche) must present a negative urine pregnancy test at the time of trial enrollment.
• Women of childbearing age must commit to using and adequate contraception method.
• Subjects capable of complying with a dosage regimen.
• Subjects owning a smartphone to register symptoms and medication consumption.

You may not qualify if:

• Subjects polysensitized to other aeroallergens with clinically relevant symptoms.
• Subjects who have received previous immunotherapy in the preceding 5 years to any of the tested allergens or a cross-reactive allergen or are currently receiving immunotherapy with any allergen.
• Patients in whom 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 may not be included.
• Subjects with uncontrolled severe asthma, and/or with FEV1 \<80% of baseline despite adequate pharmacological treatment by the time of the enrolment.
• Subjects on treatment with ß-blockers.
• Subjects on treatment with immunosuppressive or biological drugs.
• Subjects who are unstable by the time of enrolment (respiratory infection, febrile process, acute pruritus, etc.).
• Subjects with chronic urticaria during the last 2 years, severe anaphylaxis or with hereditary angioedema history.
• Subjects with any pathology in which the administration of adrenaline is contraindicating (hyperthyroidism, hypertension, heart disease, etc.) according to the investigator discretion.
• Subjects with any other disease not related to moderate rhinoconjunctivitis or asthma, but potentially serious and that could interfere with treatment and follow-up (epilepsy, psychomotor disorders, diabetes, malformations, multi-surgery, nephropathy, etc.), according to the investigator discretion.
• Subjects with severe autoimmune disease (thyroiditis, lupus, etc.), tumour diseases or diagnosed with immunodeficiencies.
• Subject whose condition prevents him/her from offering cooperation and/or who presents severe psychiatric disorders, according to the investigator discretion.
• Subjects with known allergy to the other components of the investigational product other than allergen study.
• Subjects with lower airway diseases other than asthma such as emphysema or bronchiectasis.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Inmunotek S.L.: lead
• LAT Research: collaborator
• Xolomon Tree S.L.: collaborator

Study Sites (1)

Fundación CIDEA

Buenos Aires, Paraguay, 2035, Argentina

Location

Related Publications (7)

• Malling HJ. The position of immunotherapy in the European Academy of Allergology and Clinical Immunology. J Investig Allergol Clin Immunol. 1997 Sep-Oct;7(5):356-7. No abstract available.

  PMID: 9416545 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

• 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

• Nieto A, Mazon A, Nieto M, Ibanez E, Jang DT, Calaforra S, Alba P, Perez-Frances C, Llusar R, Montoro J, de Mateo A, Alamar R, El-Qutob D, Fernandez J, Moral L, Toral T, Anton M, Andreu C, Ferrer A, Flores IM, Cerda N, Del Pozo S, Caballero R, Subiza JL, Casanovas M. First-in-human phase 2 trial with mite allergoids coupled to mannan in subcutaneous and sublingual immunotherapy. Allergy. 2022 Oct;77(10):3096-3107. doi: 10.1111/all.15374. Epub 2022 May 27.

  PMID: 35570712 BACKGROUND

• Pfaar O, Klimek L, Gerth van Wijk R. Clinically relevant outcome measures for new pharmacotherapy, allergen avoidance and immunotherapy trials in allergic rhinoconjunctivitis. Curr Opin Allergy Clin Immunol. 2015 Jun;15(3):197-203. doi: 10.1097/ACI.0000000000000164.

  PMID: 25899694 BACKGROUND

• Caballero R, Grau A, Javaloyes G, Del Pozo S, Leon MA, Romero M, Casanovas M. Combination of Allergic Asthma Symptom and Medication Scores in Allergen Immunotherapy Trials: A Proposal. Int Arch Allergy Immunol. 2021;182(7):571-573. doi: 10.1159/000513543. Epub 2021 Jan 26. No abstract available.

  PMID: 33498057 BACKGROUND

• Passalacqua G, Baena-Cagnani CE, Bousquet J, Canonica GW, Casale TB, Cox L, Durham SR, Larenas-Linnemann D, Ledford D, Pawankar R, Potter P, Rosario N, Wallace D, Lockey RF. Grading local side effects of sublingual immunotherapy for respiratory allergy: speaking the same language. J Allergy Clin Immunol. 2013 Jul;132(1):93-8. doi: 10.1016/j.jaci.2013.03.039. Epub 2013 May 15.

  PMID: 23683513 BACKGROUND

MeSH Terms

Conditions

Rhinitis, Allergic; Dust Mite Allergy; Hypersensitivity; Rhinitis

Condition Hierarchy (Ancestors)

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

Study Officials

• Jorge Fernando Maspero, MD, PhD

  Fundación CIDEA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miguel Casanovas, MD, PhD

CONTACT

(+34) 691490175; mcasanovas@inmunotek.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the trial, both the investigator and the subjects included will be unaware of the treatment each subject is receiving. Blinding is intended to minimize potential biases resulting from differences in treatment or assessment of subjects. It is also intended to reduce as much as possible the interpretation of the results that could arise as a consequence of the investigator or the subject knowing the assigned treatment. The person in charge of data analysis will also not know the treatment assigned to each subject until the database has been closed. So that neither the subject nor the investigator will know which treatment each subject is receiving, all trial medication will be identical in outer packaging and appearance.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, randomised, double-blind, placebo-controlled clinical trial.

Study Record Dates

• First Submitted: November 17, 2022
• First Posted: December 7, 2022
• Study Start: November 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 23, 2023

Record last verified: 2022-11

Locations

AR (1)