Clinical trial NCT05400811: Efficacy and Safety Evaluation for the Treatment of HDM Induced Allergic Asthma and Rhinitis/Rhinoconjunctivitis
Official title: Prospective, Randomised, DBPC, Double-dummy, Multicenter CT of Efficacy and Safety With IT in Patients With Controlled Mild to Moderate Allergic Asthma and Rhinitis/Rhinoconjunctivitis, Allergic to D. Pteronyssinus and/or D. Farinae.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: House Dust Mite Allergy
Perennial Allergic Rhinitis
Allergic Rhinoconjunctivitis
Allergic Asthma
Keywords: Rhinitis/ Rhinoconjunctivitis
Allergy
Immunotherapy
Mild to moderate asthma
Lead sponsor: Inmunotek S.L.
Sponsor class: INDUSTRY
Collaborators: name: BioClever 2005 S.L.
name: NTS hub S.L
First posted: 2022-06-02
Enrollment: 400
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, randomized, placebo-controlled, double-blind, double-dummy, multi-center trial
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: CSMS: Combined Symptoms and Medication Score
timeFrame: 12 months
Secondary outcomes:
measure: Asthma symptom-free days
timeFrame: 12 months
measure: Rhinitis / rhinoconjunctivitis symptom-free days
timeFrame: 12 months
measure: Asthma medication-free days
timeFrame: 12 months
measure: Rhinitis / rhinoconjunctivitis medication-free days
timeFrame: 12 months
measure: Respiratory function_FEV1
timeFrame: Baseline, month 6, month 12
measure: Respiratory function_PEF
timeFrame: Baseline, month 6, month 12
measure: Asthmatic exacerbations
timeFrame: 12 months
measure: Clinical benefit
timeFrame: 12 months
measure: Immunological parameters
timeFrame: 12 months
measure: Quality of life associated with asthma (AQLQ)
timeFrame: 12 months
measure: Quality of life associated with rhinoconjunctivitis (RQLQ)
timeFrame: Baseline, month 6, month 12
measure: Questionnaire for asthma control (ACQ)
timeFrame: 12 months
measure: Visual Analogue Scale (VAS)
timeFrame: 12 months
measure: Consumption of health resources
timeFrame: 12 months
measure: Safety parameters
timeFrame: 12 months
measure: Number of Local Adverse Reactions
timeFrame: 12 months
measure: Number of Systemic Adverse Reactions
timeFrame: 12 months
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital Universitario de Elche
state: Alicante
city: Ibiza
country: Spain
facility: Policlínica Nuestra Sra del Rosario
state: Baleares
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital de Terrassa
state: Barcelona
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: San Cristóbal de La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Santa Cruz De Tenerife
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Alicante
country: Spain
facility: Centro Médico Quiron Salud Alicante
city: Melilla
country: Spain
facility: Clínica RUSADIR
city: Málaga
country: Spain
facility: Hopital Quirón Salud Málaga
city: Málaga
country: Spain
facility: Clinica del Dr.Pérez Estrada Cornejo
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Pontevedra
country: Spain
facility: Complexo Hospitalario Universitario de Pontevedra
city: Valencia
country: Spain
facility: Hospital Univeristario y Politécnico La Fe
city: Vila-real
country: Spain
facility: Hospital Universitario de la Plana
Study officials:
affiliation: Hospital of Navarra
name: Ana Isabel Tabar Purroy, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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: 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.
citation: 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.
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: 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.