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

Inmunotek S.L.400 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

400

Conditions

House Dust Mite Allergy Perennial Allergic Rhinitis

Interventions

MM09 allergoid-mannan conjugates subcutaneous (3.000 UTm/mL)BIOLOGICAL

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)BIOLOGICAL

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)BIOLOGICAL

Mixture of allergen extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae conjugated to mannan at 9.000 UTm/mL for sublingual administration.

Placebo subcutaneousBIOLOGICAL

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

Placebo sublingualBIOLOGICAL

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

Eligibility

Sex: ALLMin age: 12 YearsMax age: 60 Years

Medical Language ↔ Plain English

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.

Locations (16)

Hospital Universitario de Elche

Elche, Alicante, Spain

Policlínica Nuestra Sra del Rosario

Ibiza Town, Balearic Islands, Spain

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona, Spain

Hospital de Terrassa

Terrassa, Barcelona, Spain

Hospital Universitario de Navarra

Pamplona, Navarre, Spain

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain

Hospital Universitario A Coruña

A Coruña, Spain

Hospital General Universitario de Alicante

Alicante, Spain

Centro Médico Quiron Salud Alicante

Alicante, Spain

Hopital Quirón Salud Málaga

Málaga, Spain

...and 6 more locations

Outcomes

Primary Outcomes

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

Time frame: 12 months

Secondary Outcomes

Asthma symptom-free days

Number of days that subjects have no symptoms related to asthma

Time frame: 12 months

Rhinitis / rhinoconjunctivitis symptom-free days

Number of days that subjects have no symptom related to rhinitis / rhinoconjunctivitis.

Time frame: 12 months

Asthma medication-free days

Number of days that subjects need no medication for treatment of asthma.

Time frame: 12 months

Rhinitis / rhinoconjunctivitis medication-free days

Number of days that subjects need no medication for treatment of Rhinitis / rhinoconjunctivitis.

Time frame: 12 months

Respiratory function_FEV1

Measurement of Forced Expiratory Volume in 1 Second (FEV1) %

Time frame: Baseline, month 6, month 12

Respiratory function_PEF

Peak Expiratory Flow (PEF) \[velocity\]

Time frame: Baseline, month 6, month 12

Asthmatic exacerbations

Time elapsed until the first appearance of asthmatic exacerbations, number, duration and severity.

Time frame: 12 months

Clinical benefit

Time to onset of clinical benefit

Time frame: 12 months

Immunological parameters

Analyses of total and specific IgE, specific IgE index / total IgE, specific IgG4 and Anti-Saccharomyces cerevisiae (ASCA) IgA\&IgG.

Time frame: 12 months

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.

Time frame: 12 months

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".

Time frame: Baseline, month 6, month 12

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

Time frame: 12 months

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.

Time frame: 12 months

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

Time frame: 12 months

Safety parameters

Global rate and severity of AE per administration and per subject

Time frame: 12 months

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)

Time frame: 12 months

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.

Time frame: 12 months

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

Overview

Conditions

Interventions

Eligibility

Locations (16)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts