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

Allergic Asthma Clinical Trial

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05400811
• Other study ID #: MM09-SIT-040
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: December 2022
• Est. completion date: July 2025

Study information

• Verified date: April 2022
• Source: Inmunotek S.L.
• Contact: Miguel Casanovas, MD, PhD
• Phone: 912908942
• Email: mcasanovas[@]inmunotek.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: July 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 60 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Allergic Asthma
• Allergic Rhinoconjunctivitis
• Asthma
• Conjunctivitis
• House Dust Mite Allergy
• Perennial Allergic Rhinitis
• Rhinitis
• Rhinitis, Allergic
• Rhinitis, Allergic, Perennial

Intervention

Biological:
• 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.
• 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.
• 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.
• Placebo subcutaneous
The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.
• Placebo sublingual
The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.

Locations

Country	Name	City	State
Spain	Hospital Universitario A Coruña	A Coruña
Spain	Centro Médico Quiron Salud Alicante	Alicante
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Universitario de Elche	Elche	Alicante
Spain	Hospital Sant Joan de Déu	Esplugues De Llobregat	Barcelona
Spain	Policlínica Nuestra Sra del Rosario	Ibiza	Baleares
Spain	Clinica del Dr.Pérez Estrada Cornejo	Málaga
Spain	Hopital Quirón Salud Málaga	Málaga
Spain	Hospital Universitario Regional de Málaga	Málaga
Spain	Clínica RUSADIR	Melilla
Spain	Hospital Universitario de Navarra	Pamplona	Navarra
Spain	Complexo Hospitalario Universitario de Pontevedra	Pontevedra
Spain	Hospital Universitario de Canarias	San Cristóbal de La Laguna	Santa Cruz De Tenerife
Spain	Hospital de Terrassa	Terrassa	Barcelona
Spain	Hospital Univeristario y Politécnico La Fe	Valencia
Spain	Hospital Universitario de la Plana	Vila-real

Sponsors (3)

Lead Sponsor	Collaborator
Inmunotek S.L.	BioClever 2005 S.L., NTS hub S.L

Country where clinical trial is conducted

Spain, 

References & 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. Review. — View Citation

González JL, Zalve V, Fernández-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. — View Citation

Manzano AI, Javier Cañada F, Cases B, Sirvent S, Soria I, Palomares O, Fernández-Caldas E, Casanovas M, Jiménez-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. — View Citation

Sirvent S, Soria I, Cirauqui C, Cases B, Manzano AI, Diez-Rivero CM, Reche PA, López-Relaño J, Martínez-Naves E, Cañada FJ, Jiménez-Barbero J, Subiza J, Casanovas M, Fernández-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. — View Citation

Soria I, Alvarez J, Manzano AI, López-Relaño J, Cases B, Mas-Fontao A, Cañada FJ, Fernández-Caldas E, Casanovas M, Jiménez-Barbero J, Palomares O, Viñals-Flórez 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. — View Citation

Soria I, López-Relaño J, Viñuela M, Tudela JI, Angelina A, Benito-Villalvilla C, Díez-Rivero CM, Cases B, Manzano AI, Fernández-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Asthma symptom-free days	Number of days that subjects have no symptoms related to asthma	12 months
Secondary	Rhinitis / rhinoconjunctivitis symptom-free days	Number of days that subjects have no symptom related to rhinitis / rhinoconjunctivitis.	12 months
Secondary	Asthma medication-free days	Number of days that subjects need no medication for treatment of asthma.	12 months
Secondary	Rhinitis / rhinoconjunctivitis medication-free days	Number of days that subjects need no medication for treatment of Rhinitis / rhinoconjunctivitis.	12 months
Secondary	Respiratory function_FEV1	Measurement of Forced Expiratory Volume in 1 Second (FEV1) %	Baseline, month 6, month 12
Secondary	Respiratory function_PEF	Peak Expiratory Flow (PEF) [velocity]	Baseline, month 6, month 12
Secondary	Asthmatic exacerbations	Time elapsed until the first appearance of asthmatic exacerbations, number, duration and severity.	12 months
Secondary	Clinical benefit	Time to onset of clinical benefit	12 months
Secondary	Immunological parameters	Analyses of total and specific IgE, specific IgE index / total IgE, specific IgG4 and Anti-Saccharomyces cerevisiae (ASCA) IgA&IgG.	12 months
Secondary	Quality of life associated with asthma (AQLQ)	The quality of life associated with asthma will be measured using the Asthma Quality of Life Questionnaire (AQLQ).; AQLQ consists of 32 items and 4 domains (limitations in activities, symptoms, emotional and environmental). Each item is scored from 1=no impairment to 7=severe impairment.	12 months
Secondary	Quality of life associated with rhinoconjunctivitis (RQLQ)	The quality of life associated with rhinoconjunctivitis will be measured using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ).; RQLQ it consists of 28 items (questions) and 7 domains (Activities, sleep, general symptoms, practical problems, nose symptoms, eye and emotional symptoms).; The score of each item for all domains, except for the emotional one, ranges from "0=Nothing bothered me" to "6=It has bothered me a lot". The emotional domain score ranges from "0=Never" to "6=Always".	Baseline, month 6, month 12
Secondary	Questionnaire for asthma control (ACQ)	Asthma control will be measured following the ACQ questionnaire.; The ACQ questionnaire consists of 7 questions (ACQ-7) or 6 questions (ACQ-6). In questions 1-6, patients recall their experience during the last 7 days and answer using a scale of 7 points (from "0 = fully controlled" to "6 = extremely poorly controlled"). The seventh question, which refers to the% FEV1 of the reference value, must be completed by an employee of the site. The questionnaire score is the mean of the 7 responses (ACQ-7) or 6 responses (ACQ-6).; The interpretation of the scores is as follows: Less than or equal to 0.75: Adequate control of asthma From 0.75 to 1.50: Partially controlled asthma More than 1.50: Inadequate asthma control	12 months
Secondary	Visual Analogue Scale (VAS)	Visual Analogue Scale in which the subject has to indicate in a straight line of 10 cm how he/she feels regarding to his allergy symptoms. Being left side "0 = very bad" and right side "10 = very well".; VAS scale will also be completed by the investigator answering how he/she thinks that the patient feels.	12 months
Secondary	Consumption of health resources	For each patient, the number of times that due to allergy symptoms has done the following will be counted: have visited the family doctor; have made an unscheduled visit to the specialist; has gone to the emergency room; has been hospitalized; have needed to contact the doctor by phone	12 months
Secondary	Safety parameters	Global rate and severity of AE per administration and per subject	12 months
Secondary	Number of Local Adverse Reactions	Local adverse reactions are those that appear at the site of the administration. They are classified into: Immediate (it appears during the first 30 minutes from the administration of investigational product) and Late (it appears after the first 30 minutes from the administration of investigational product)	12 months
Secondary	Number of Systemic Adverse Reactions	Systemic adverse reactions are those that appear in other parts of the body other than the site of administration.Their severity will be classified following the indications proposed by the World Allergy Organization (WAO) in 2010.	12 months