Multicenter clinical trial to evaluate efficacy and safety of sublingual immunotherapy in patients allergic to house mites, with rhinitis/rhinoconjunctivitis with or without mild to moderate asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Inmunotek S.L.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

16 Jul 2025 → ongoing

Decision date (initial)

2024-07-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective is to evaluate the efficacy of Sublingual MM09 at dose of 30.000 TU/mL compared to placebo administered for 12 months, in subjects aged 12-65 years with intermittent or persistent moderate-to-severe rhinitis/rhinoconjunctivitis with or without mild-to-moderate controlled intermittent or persistent asthma, allergic to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae.

Secondary objectives 6

1. To evaluate the clinical efficacy of Sublingual MM09 compared to placebo with the mean of the daily scores (RCSMS) adjusted to baseline scores.
2. To assess the clinical efficacy of Sublingual MM09 compared to placebo adjusting to regional values.
3. To estimate the safety and clinical tolerability of Sublingual MM09 compared to placebo.
4. To assess the clinical benefit of Sublingual MM09 with regard to different efficacy parameters in comparison to placebo and baseline. placebo and baseline.
5. To evaluate the impact of Sublingual MM09 on the immunological status of the participants in comparison to placebo and baseline.
6. To evaluate the clinical impact of Sublingual MM09 with regard to health-related Quality of Life in comparison to placebo and baseline.

Conditions and MedDRA coding

Aetiological treatment of moderate to severe rhinitis/rhinoconjunctivitis with or without mild to moderate controlled allergic asthma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participants who have signed and dated Informed Consent Form (ICF)
2. Female or male aged 12 to 65 years, both included, at the time of signature of the ICF
3. Participants with confirmed clinical history of inhalation allergy with intermittent or persistent moderate-severe rhinitis/ rhinoconjunctivitis according to the ARIA classification of at least 1 year of duration (treated with anti-allergic medication) with or without mild-moderate controlled intermittent or persistent asthma according to the definition of GINA 2022 caused by Dermatophagoides pteronyssinus and / or Dermatophagoides farinae).
4. Participants with positive skin prick test and a wheal major diameter ≥ 5 mm to a standardized allergen extract of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae
5. Women of childbearing age (i.e., following menarche and until postmenopause, defined as no menses for 12 months without an alternative medical cause, or non-subject to permanent sterilisation methods, such as hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must have a urine pregnancy test negative result before enrolling the study
6. Women of childbearing age must commit to using an adequate contraception method
7. Participants capable of complying with dosage regimen.
8. Participants owning a smartphone to register symptoms and medication consumption
9. Participants not sensitized to any other clinically relevant allergen or sensitized with the following characteristics (sensitization to other allergens will be assessed through skin prick test in Europe and LATAM and through IgE levels in China): a. Participants sensitized to dander (with a positive skin prick test for dander or IgE ≥ 0.35 kU/L), provided that they have occasional exposure and symptoms. b. Participants sensitized to endemic pollen (with a positive skin prick test or IgE ≥0.35 kU/L) will be scheduled to be included so that the pollen season does not coincide with the Baseline Evaluation Period nor with one month before and after the Main Evaluation Period. In LATAM, grass sensitized participants will not be included
10. Participants not sensitized to moulds, cockroach, Blomia tropicalis or other geographically relevant mites (negative skin prick test or IgE < 0.7 kU/L)
11. Participants with a RCSMS ≥ 3 out of 6 recorded for at least 10 days in the baseline evaluation period, corresponding to moderate-to-severe allergic rhinitis /rhinoconjunctivitis
12. Participants with 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

Exclusion criteria 27

1. Participants who have received previous immunotherapy to any of the tested allergen during the last 5 years or any desensitization process in the last 2 years (e.g., oral immunotherapy [OIT], milk, or egg) before the second screening visit (S2), or currently receiving immunotherapy with any other allergen
2. Those cases in which allergen-specific immunotherapy (AIT) would be a contraindication according to the criteria of European Allergy and Clinical Immunology Immunotherapy Subcommittee
3. Asthmatic participants with forced expiratory volume in the first second (FEV1) <80% (following at least a 6-hour washout of short-acting beta2 agonists [SABA] and 12-hour washout of long-acting beta2 agonists [LABA]) despite pharmacological treatment by the time of enrolment
4. Participants with uncontrolled asthma, according to GINA 2022, asthma with poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma) and/or frequent exacerbations (≥2/year) requiring oral corticosteroids (OCS), or serious exacerbations (≥1/year) requiring hospitalization
5. Participants with severe asthma, according to GINA 2022,(2) on Step 4 or 5 treatment, who had poor symptom control and had good adherence and inhaler technique
6. Participants on treatment with β-blockers or angiotensin-converting enzyme (ACE) inhibitor
7. Participants on treatment with immunosuppressive or biological drugs
8. Participants who had not had a long enough washout/withdrawal period at the first screening visit (S1) according to criteria in study protocol (See Table 6 in Section 9.5.3) before undergoing allergen diagnostic tests (skin prick test or IgE analysis)
9. Unstable participants who have suffered a respiratory tract infection and/or asthma exacerbation within 4 weeks prior to the first screening visit (S1)
10. Participants who have suffered chronic urticaria severe anaphylaxis, or with hereditary angioedema history within 2 years prior to first screening visit (S1)
11. Participants having any contraindication for the use of adrenaline (e.g., hyperthyroidism, heart disease, or hypertension) according to the investigator’s criteria
12. Participants with other severe diseases not related to allergic rhinitis or asthma that could interfere with the study treatment or the follow-up
13. Participants with severe and unresponsive to treatment autoimmune diseases (e.g., thyroiditis or lupus), tumoral diseases or immunodeficiencies
14. Participants that could not comply with the study protocol, according to the investigator's criteria, or have a serious mental illness
15. Participants with known allergy to any of the components of the study treatment other than study allergens
16. Participants who had a complication(s) of any nasal disease (including nasal polyp, nasal septal deviation, and hypertrophic rhinitis, drug-induced rhinitis and/or non-allergic rhinitis) affecting an appropriate evaluation of the efficacy and/or safety, according to investigator's criteria
17. Participants who had a nasal surgery within 6 months prior to the first screening visit (S1) or have programmed or anticipated nasal surgery during the trial period
18. Participants with a lesion in the oral cavity that could confound the safety profile of the study treatment, according to the investigator's criteria
19. Participants who required treatment with antihistamines and/or corticosteroids for other purposes than alleviating symptoms of allergic rhinitis (except temporal use for diseases such as common colds)
20. Participants with lower respiratory tract diseases different from asthma as emphysema, bronchiectasis or chronic obstructive pulmonary disease
21. Breastfeeding or pregnant women
22. Participants who are immediate family members of the investigator
23. Concurrent participation in other clinical trials or previous participation within 30 days prior to first screening visit (S1)
24. Participants with history of serious systemic reactions, including food, Hymenoptera venom, medications, etc.
25. Participants expected to have marked changes (e.g, moving) in the circumstances of life during the study
26. Participants who plan to start using anti-mite bedding or similar equipment during the study
27. Participants who are considered inappropriate for the study, according to the investigator criteria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The mean of the daily Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS) during the Main Evaluation Period (the last 4 week of IMP treatment) by means of the Participant’s Diary

Secondary endpoints 15

1. Rhinitis/Rhinoconjunctivitis Symptom Score (RSS)
2. Rhinitis/Rhinoconjunctivitis Medication Score (RMS).
3. Asthma and Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (ACSMS).
4. Asthma Symptom Score (ASS)
5. Asthma Medication Score (AMS)
6. Asthma and Rhinitis/Rhinoconjunctivitis Symptom Score (ARSS)
7. Asthma and Rhinitis/Rhinoconjunctivitis Medication Score (ARMS)
8. Asthma and Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (ARCSMS)
9. Asthma exacerbations: Time to first exacerbation; number, duration, and severity of exacerbations
10. Immunological parameters in blood samples: - Total IgE - Specific IgE for D. pteronyssinus and D. farinae - Specific IgE for D. pteronyssinus and D. farinae /Total IgE ratio
11. Allergen profiling (ALEX technique), if serum is available
12. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
13. Participant and investigator health status perception through a Visual Analogue Scale (VAS)
14. Consumption of health resources.
15. Safety parameters: - Overall rate and severity of adverse events (AE) per administration and per participant. - Evaluation of reactions at the site of administration, systemic reactions and of any medication administered for the treatment of the AE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Inmunotek S.L.

Sponsor organisation

Inmunotek S.L.

Address

Calle Punto Mobi 5

City

Alcala De Henares

Postcode

28805

Country

Spain

Scientific contact point

Organisation

Inmunotek S.L.

Contact name

Medical Department

Public contact point

Organisation

Inmunotek S.L.

Contact name

Medical Department

Third parties 2

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications