Clinical trial NCT05641272: Clinical Trial to Evaluate the Efficacy and Safety of Polymerized, Mannan-Conjugated Dermatophagoides Allergen Extract
Official title: Prospective, Randomised, DBPC 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Allergic Rhinitis
Allergic Asthma
Allergic Rhinoconjunctivitis
Allergy to House Dust Mite
Keywords: Allergy
Mites
Hypersensitivity
Rhinitis
Rhinoconjunctivitis
Lead sponsor: Inmunotek S.L.
Sponsor class: INDUSTRY
Collaborators: name: LAT Research
name: Xolomon Tree S.L.
First posted: 2022-12-07
Enrollment: 90
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomised, double-blind, placebo-controlled clinical trial.
Primary purpose: PREVENTION

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).

Detailed description: Allergen-specific immunotherapy (AIT) has been shown to be effective in relieving symptoms, reducing medication use, and improving quality of life in patients with respiratory allergies). This is thought to be due to the induction of a state of tolerance to specific allergens with long-lasting effects after discontinuation of treatment. And it is accepted that immunotherapy is the only available method for allergists to improve or cure, partially or definitely, an allergic process The study population of this clinical trial will comprise subjects allergic to mites (Dermatophagoides pteronyssinus and/or D. farinae) with symptoms of moderate-severe rhinitis/rhinoconjunctivitis with or without mild to severe controlled asthma, suitable to allergen immunotherapy.

The primary efficacy endpoint will be the combined rhinitis/rhinoconjunctivitis symptom and medication score.

Every single day from the beginning of the administration of the investigational drug (V2-VF), the subject will be asked to score and register his/her symptoms and record medication consumption in an electronic diary following the instructions of the application. This diary will provide the symptom score and medication consumption for each subject during the trial.

Eligibility criteria: Inclusion Criteria:

1. Signed Informed Consent Form.
2. Male or female, aged between 12 and 60 years, both included.
3. 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.
4. Combined Symptom and Medication Score for moderate to severe rhinitis/rhinoconjunctivitis (RCSMS) ≥ 1,8 out of 3.
5. 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.
6. 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.
7. 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.
8. Subjects with negative skin prick test to mold. In case specific IgE determination have been performed, the result must be \<0.35 kU/L.
9. Women of childbearing age (since menarche) must present a negative urine pregnancy test at the time of trial enrollment.
10. Women of childbearing age must commit to using and adequate contraception method.
11. Subjects capable of complying with a dosage regimen.
12. Subjects owning a smartphone to register symptoms and medication consumption.

Exclusion Criteria:

1. Subjects polysensitized to other aeroallergens with clinically relevant symptoms.
2. 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.
3. 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.
4. Subjects with uncontrolled severe asthma, and/or with FEV1 \<80% of baseline despite adequate pharmacological treatment by the time of the enrolment.
5. Subjects on treatment with ß-blockers.
6. Subjects on treatment with immunosuppressive or biological drugs.
7. Subjects who are unstable by the time of enrolment (respiratory infection, febrile process, acute pruritus, etc.).
8. Subjects with chronic urticaria during the last 2 years, severe anaphylaxis or with hereditary angioedema history.
9. Subjects with any pathology in which the administration of adrenaline is contraindicating (hyperthyroidism, hypertension, heart disease, etc.) according to the investigator discretion.
10. 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.
11. Subjects with severe autoimmune disease (thyroiditis, lupus, etc.), tumour diseases or diagnosed with immunodeficiencies.
12. Subject whose condition prevents him/her from offering cooperation and/or who presents severe psychiatric disorders, according to the investigator discretion.
13. Subjects with known allergy to the other components of the investigational product other than allergen study.
14. Subjects with lower airway diseases other than asthma such as emphysema or bronchiectasis.
15. Pregnant or breastfeeding women.
16. Subjects who are immediate family members of researchers.
17. Concurrent participation in other clinical trials or previous participation within 30 days prior to inclusion.
18. History of severe systemic reactions, including food, hymenoptera venom, etc.
19. Subjects who have suffered a respiratory tract infection and/or asthma exacerbation within 4 weeks prior to screening.
20. Subjects with a history of significant renal disease or chronic liver disease.

Primary outcomes:
measure: Rhinitis/rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS)
timeFrame: 6 months
Secondary outcomes:
measure: Rhinitis/ Rhinoconjunctivitis Symptom Score (RSS)
timeFrame: 6 months
measure: Rhinitis/Rhinoconjunctivitis Medication Score (RMS)
timeFrame: 6 months
measure: Asthma Combined Symptom and Medication Score (ACSMS)
timeFrame: 6 months
measure: Asthma Symptom Score (ASS)
timeFrame: 6 months
measure: Asthma Medication Score (AMS)
timeFrame: 6 months
measure: Asthma and Rhinitis/Rhinoconjunctivitis Symptom Score (ARSS)
timeFrame: 6 months
measure: Asthma and Rhinitis/Rhinoconjunctivitis Medication Score (ARMS)
timeFrame: 6 months
measure: Asthma and Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (ARCSMS)
timeFrame: 6 months
measure: Symptom free-days (rhinitis/rhinoconjunctivitis, asthma)
timeFrame: 6 months
measure: Medication free days (rhinitis/rhinoconjunctivitis, asthma)
timeFrame: 6 months
measure: Asthma exacerbations
timeFrame: 4 months
measure: Clinical benefit
timeFrame: 6 months
measure: Respiratory function
timeFrame: 6 months
measure: Number of eosinophil
timeFrame: 6 months
measure: Immunological parameters in blood
timeFrame: 6 months
measure: Immunological parameters in nasal mucosa.
timeFrame: Month 2 and month 7
measure: Asthma Quality of Life Questionnaire (AQLQ)
timeFrame: Month 2 and month 7
measure: Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
timeFrame: 6 months
measure: Asthma Control Questionnaire (ACQ 6)
timeFrame: 4 months
measure: Asthma Control Questionnaire (ACQ 7)
timeFrame: 6 months
measure: Visual Analogue Scales (VAS)
timeFrame: 7 months
measure: Consumption of health resources
timeFrame: 7 months
measure: Security parameters
timeFrame: Month 2 and month 7
measure: Number of Local Adverse Reactions
timeFrame: 6 months
measure: Number of Systemic Adverse Reactions
timeFrame: 6 months
measure: Number of Adverse Reactions to any medication
timeFrame: 7 months
measure: Treatment adherence
timeFrame: 6 months
measure: Compliance of the electronic diary
timeFrame: 6 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Fundación CIDEA
state: Paraguay
Study officials:
affiliation: Fundación CIDEA
name: Jorge Fernando Maspero, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.