Evaluation of Efficacy and Safety of Sublingual MM09 in Patients with Allergic Rhinitis/Rhinoconjunctivitis and Mild to Moderate Asthma Due to Dermatophagoides spp.
- Trial ID
- 2023-505918-14-00
- Protocol
- MM09-SLG-058
- Sponsor
- Inmunotek S.L.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **efficacy** of Sublingual MM09 at a dose of 30,000 TU/mL compared to placebo over a 12-month period. This study targets individuals aged 12-65 years with intermittent or persistent moderate-to-severe **rhinitis/rhinoconjunctivitis** with or without mild-to-moderate controlled intermittent or persistent **asthma**, who are allergic to **Dermatophagoides pteronyssinus** and/or **Dermatophagoides farinae**. The clinical relevance of this objective lies in its potential to provide an effective treatment option for patients suffering from these allergic conditions, thereby improving their quality of life and reducing the burden of symptoms.
Secondary objectives include:
- Evaluating the clinical efficacy of Sublingual MM09 compared to placebo using the mean of the daily scores (RCSMS) adjusted to baseline scores.
- Assessing the clinical efficacy of Sublingual MM09 compared to placebo with adjustments to regional values.
- Estimating the safety and clinical tolerability of Sublingual MM09 compared to placebo.
- Assessing the clinical benefit of Sublingual MM09 with regard to different efficacy parameters in comparison to placebo and baseline.
- Evaluating the impact of Sublingual MM09 on the immunological status of the participants in comparison to placebo and baseline.
- Evaluating the clinical impact of Sublingual MM09 with regard to health-related Quality of Life in comparison to placebo and baseline.
Participants
The clinical trial involves a total of **736 participants** aged between **12 and 65 years**, inclusive, who are diagnosed with intermittent or persistent moderate-to-severe **rhinitis/rhinoconjunctivitis** with or without mild-to-moderate controlled intermittent or persistent asthma. Both **male and female** subjects are included in the study population. Participants were selected based on specific criteria, including a confirmed clinical history of inhalation allergy caused by **Dermatophagoides pteronyssinus** and/or **Dermatophagoides farinae**, and a positive skin prick test. The trial population is required to have a smartphone to register symptoms and medication consumption, indicating a consideration for technological accessibility. Participants are not sensitized to moulds, cockroach, Blomia tropicalis, or other geographically relevant mites, and must not be sensitized to any other clinically relevant allergen unless specific conditions are met. The study does not provide information on the general health status or lifestyle considerations such as diet or physical activity of the participants.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of **sublingual immunotherapy** in patients with moderate to severe **rhinitis/rhinoconjunctivitis** with or without mild to moderate controlled **allergic asthma**. The trial will involve the administration of Sublingual MM09, a sublingual spray solution containing **Dermatophagoides farinae extract** and **Dermatophagoides pteronyssinus extract**, compared to a placebo solution identical in composition but without active ingredients. The study is set to commence recruitment in August 2024 and is expected to conclude by August 2028, with a total treatment period of 12 months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, clinical history, and sensitization to allergens. Following successful screening, participants will be randomized to receive either the active treatment or placebo. The trial will include regular follow-up visits to monitor safety, adherence, and efficacy, with assessments including symptom and medication scores, immunological parameters, and quality of life questionnaires. The primary endpoint will be the mean daily Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS) during the main evaluation period, which is the last four weeks of treatment. Secondary endpoints will include various symptom and medication scores, asthma exacerbations, and safety parameters.
The expected length of participant involvement is approximately 12 months, with conditions for early termination including non-compliance with the dosage regimen, adverse events, or withdrawal of consent. Participants will be required to maintain a diary to record symptoms and medication use, and women of childbearing age must use adequate contraception and have a negative pregnancy test before enrollment. The trial aims to provide comprehensive data on the efficacy and safety of the investigational product in the target population, contributing to the understanding and management of allergic conditions related to house dust mites.
Treatment
The clinical trial involves the administration of **Sublingual MM09**, a sublingual spray solution designed for the treatment of patients with rhinitis/rhinoconjunctivitis, with or without mild to moderate asthma, who are allergic to **Dermatophagoides pteronyssinus** and/or **Dermatophagoides farinae**. The active substances in this experimental medication are extracts from **Dermatophagoides farinae** and **Dermatophagoides pteronyssinus**, both classified as structurally diverse allergens. The pharmaceutical form of Sublingual MM09 is a sublingual spray, and it is administered via sublingual use. The dosage is set at 30,000 TU/mL, with a maximum daily dose of 200 microliters, and the treatment period extends over 12 months. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
The study also includes a placebo group, receiving a solution identical in composition to the active treatment but devoid of active ingredients. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in the same manner as the active treatment, using a sublingual spray solution, and follows the same dosing schedule to provide a valid comparison of efficacy and safety between the active treatment and the placebo.
Efficacy
The efficacy of the investigational medicinal product, Sublingual MM09, will be assessed in a prospective, randomized, double-blind, placebo-controlled multicenter clinical trial. The primary endpoint for evaluating efficacy is the mean of the daily Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS) during the Main Evaluation Period, which is the last four weeks of the investigational medicinal product treatment. This will be measured using the Participant’s Diary.
Secondary endpoints include a variety of symptom and medication scores such as the Rhinitis/Rhinoconjunctivitis Symptom Score (RSS), Rhinitis/Rhinoconjunctivitis Medication Score (RMS), and the Asthma and Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (ARCSMS). Additional assessments will include the Asthma Symptom Score (ASS), Asthma Medication Score (AMS), and the evaluation of asthma exacerbations, including time to first exacerbation, number, duration, and severity. Immunological parameters will be analyzed through blood samples, focusing on total **IgE**, specific **IgE** for Dermatophagoides pteronyssinus and Dermatophagoides farinae, and the specific **IgE**/total **IgE** ratio. Allergen profiling using the ALEX technique will be conducted if serum is available.
Quality of life will be assessed using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and both participant and investigator health status perceptions will be evaluated through a Visual Analogue Scale (VAS). The consumption of health resources will also be monitored. Safety parameters will be evaluated by recording the overall rate and severity of adverse events per administration and per participant, including reactions at the site of administration and systemic reactions, as well as any medication administered for the treatment of adverse events.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants who have signed and dated Informed Consent Form (ICF)
- Female or male aged 12 to 65 years, both included, at the time of signature of the ICF
- 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).
- 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
- 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
- Women of childbearing age must commit to using an adequate contraception method
- Participants capable of complying with dosage regimen.
- Participants owning a smartphone to register symptoms and medication consumption
- 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
- Participants not sensitized to moulds, cockroach, Blomia tropicalis or other geographically relevant mites (negative skin prick test or IgE < 0.7 kU/L)
- 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
- 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
- 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
- Those cases in which allergen-specific immunotherapy (AIT) would be a contraindication according to the criteria of European Allergy and Clinical Immunology Immunotherapy Subcommittee
- 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
- 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
- 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
- Participants on treatment with β-blockers or angiotensin-converting enzyme (ACE) inhibitor
- Participants on treatment with immunosuppressive or biological drugs
- 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)
- Unstable participants who have suffered a respiratory tract infection and/or asthma exacerbation within 4 weeks prior to the first screening visit (S1)
- Participants who have suffered chronic urticaria severe anaphylaxis, or with hereditary angioedema history within 2 years prior to first screening visit (S1)
- Participants having any contraindication for the use of adrenaline (e.g., hyperthyroidism, heart disease, or hypertension) according to the investigator’s criteria
- Participants with other severe diseases not related to allergic rhinitis or asthma that could interfere with the study treatment or the follow-up
- Participants with severe and unresponsive to treatment autoimmune diseases (e.g., thyroiditis or lupus), tumoral diseases or immunodeficiencies
- Participants that could not comply with the study protocol, according to the investigator's criteria, or have a serious mental illness
- Participants with known allergy to any of the components of the study treatment other than study allergens
- 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
- 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
- Participants with a lesion in the oral cavity that could confound the safety profile of the study treatment, according to the investigator's criteria
- 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)
- Participants with lower respiratory tract diseases different from asthma as emphysema, bronchiectasis or chronic obstructive pulmonary disease
- Breastfeeding or pregnant women
- Participants who are immediate family members of the investigator
- Concurrent participation in other clinical trials or previous participation within 30 days prior to first screening visit (S1)
- Participants with history of serious systemic reactions, including food, Hymenoptera venom, medications, etc.
- Participants expected to have marked changes (e.g, moving) in the circumstances of life during the study
- Participants who plan to start using anti-mite bedding or similar equipment during the study
- Participants who are considered inappropriate for the study, according to the investigator criteria
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Portugal | Recruiting | 31 Dec 2026 | 110 |
 Spain | Recruiting | 31 Dec 2026 | 37 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Sublingual MM09 | Test | SUBLINGUAL SPRAY, SOLUTION | SUBLINGUAL USE | 200 | 12 | PRD10572368 |
The IMP placebo is a solution identical in composition to the active treatment, but without active ingredients. | Placebo | N/A | — | — | — | N/A |