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

Sponsor

Inmunotek S.L. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05400811

Collaborator

BioClever 2005 S.L. (Other), NTS hub S.L (Other)

400

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
House Dust Mite Allergy Perennial Allergic Rhinitis Allergic Rhinoconjunctivitis Allergic Asthma	Biological: MM09 allergoid-mannan conjugates subcutaneous (3.000 UTm/mL) Biological: MM09 allergoid-mannan conjugates Sublingual (3.000 UTm/mL) Biological: MM09 allergoid-mannan conjugates Sublingual (9.000 UTm/mL) Biological: Placebo subcutaneous Biological: Placebo sublingual	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, randomized, placebo-controlled, double-blind, double-dummy, multi-center trialProspective, randomized, placebo-controlled, double-blind, double-dummy, multi-center trial

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Treatment

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.

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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. Biological: Placebo sublingual The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.
Experimental: 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.	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. Biological: Placebo subcutaneous The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.
Experimental: 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.	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. Biological: Placebo subcutaneous The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.
Placebo Comparator: 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	Biological: Placebo subcutaneous The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients. Biological: Placebo sublingual The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.

Outcome Measures

Primary Outcome Measures

CSMS: Combined Symptoms and Medication Score [12 months]
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

Secondary Outcome Measures

Asthma symptom-free days [12 months]
Number of days that subjects have no symptoms related to asthma
Rhinitis / rhinoconjunctivitis symptom-free days [12 months]
Number of days that subjects have no symptom related to rhinitis / rhinoconjunctivitis.
Asthma medication-free days [12 months]
Number of days that subjects need no medication for treatment of asthma.
Rhinitis / rhinoconjunctivitis medication-free days [12 months]
Number of days that subjects need no medication for treatment of Rhinitis / rhinoconjunctivitis.
Respiratory function_FEV1 [Baseline, month 6, month 12]
Measurement of Forced Expiratory Volume in 1 Second (FEV1) %
Respiratory function_PEF [Baseline, month 6, month 12]
Peak Expiratory Flow (PEF) [velocity]
Asthmatic exacerbations [12 months]
Time elapsed until the first appearance of asthmatic exacerbations, number, duration and severity.
Clinical benefit [12 months]
Time to onset of clinical benefit
Immunological parameters [12 months]
Analyses of total and specific IgE, specific IgE index / total IgE, specific IgG4 and Anti-Saccharomyces cerevisiae (ASCA) IgA&IgG.
Quality of life associated with asthma (AQLQ) [12 months]
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.
Quality of life associated with rhinoconjunctivitis (RQLQ) [Baseline, month 6, month 12]
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".
Questionnaire for asthma control (ACQ) [12 months]
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
Visual Analogue Scale (VAS) [12 months]
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.
Consumption of health resources [12 months]
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
Safety parameters [12 months]
Global rate and severity of AE per administration and per subject
Number of Local Adverse Reactions [12 months]
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)
Number of Systemic Adverse Reactions [12 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario de Elche	Elche	Alicante	Spain	03203
2	Policlínica Nuestra Sra del Rosario	Ibiza	Baleares	Spain	07800
3	Hospital Sant Joan de Déu	Esplugues De Llobregat	Barcelona	Spain	08950
4	Hospital de Terrassa	Terrassa	Barcelona	Spain	08227
5	Hospital Universitario de Navarra	Pamplona	Navarra	Spain	31008
6	Hospital Universitario de Canarias	San Cristóbal de La Laguna	Santa Cruz De Tenerife	Spain	38320
7	Hospital Universitario A Coruña	A Coruña		Spain	15006
8	Hospital General Universitario de Alicante	Alicante		Spain	03010
9	Centro Médico Quiron Salud Alicante	Alicante		Spain	03015
10	Clínica RUSADIR	Melilla		Spain	52006
11	Hopital Quirón Salud Málaga	Málaga		Spain	29004
12	Clinica del Dr.Pérez Estrada Cornejo	Málaga		Spain	29005
13	Hospital Universitario Regional de Málaga	Málaga		Spain	29010
14	Complexo Hospitalario Universitario de Pontevedra	Pontevedra		Spain	36071
15	Hospital Univeristario y Politécnico La Fe	Valencia		Spain	46026
16	Hospital Universitario de la Plana	Vila-real		Spain	12540