Specific Immunotherapy With Mannan-Conjugated Allergoids for HDM-Allergic Rhinitis/Rhinoconjunctivitis_MM09-SIT-063.

Inmunotek

Status and phase: Enrolling; Phase 3

Conditions: Allergic Rhinitis; Allergic Asthma; Allergic Rhinoconjunctivitis

Treatments: Biological: EP-088_MM09; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07904195

MM09-SIT-069

Details and patient eligibility

About

The goal of this clinical trial is to learn whether EP-088_MM09 works to treat house dust mite allergy. It will also assess the treatment's safety. EP-088_MM09 contains modified house dust mite allergens called mannan-conjugated allergoids.

The study plans to include 250 participants aged 12 to 65 years. They will have persistent, moderate to severe nasal allergy symptoms, with or without eye symptoms. Participants may also have mild or moderate allergic asthma, provided it is controlled.

The main questions are:

• Does the treatment lower allergy symptoms and the need for symptom-relief medicines compared with a placebo?
• What medical problems or reactions occur during treatment?

Researchers will assess how well the treatment works using a score combining symptoms and medication use. The main assessment will cover four weeks after the treatment course.

Participants will be assigned by chance to receive either EP-088_MM09 or a placebo. They will have an equal chance of receiving either treatment. The placebo looks like EP-088_MM09 but contains no active ingredients. Neither participants nor study doctors will know which treatment each participant receives.

Each participant will be in the study for approximately 14 to 21 months.

Participants will:

• Attend one or two visits before starting treatment to check whether they can take part.
• Attend 12 treatment visits, approximately once a month, to receive injections under the skin. They will receive two injections at the first treatment visit and one at each later visit.
• Stay at the clinic for at least 30 minutes after each injection.
• Record symptoms and medication use daily during specified periods.
• Complete questionnaires about their symptoms and quality of life, and provide blood samples.
• Attend a final visit about one month after the last treatment visit.

Participants who are also sensitive to pollen may need a second visit before starting treatment. This is needed if their first visit falls during the relevant pollen season or within one month before or after it.

Full description

The study consists of a screening/baseline phase, a treatment phase and a final follow-up assessment.

The screening/baseline phase establishes each participant's symptom burden and use of allergy medication before treatment begins. Participants will record this information in a diary during defined assessment periods before and during treatment.

For participants who are also sensitised to pollen, the timing of assessments is designed to limit the influence of pollen exposure on the evaluation of house dust mite allergy. An additional baseline visit may therefore be required, depending on when the initial visit occurs relative to the relevant pollen season. The final symptom and medication assessment period will also be scheduled outside that pollen season, according to protocol-defined timing requirements. These scheduling arrangements account for variation in the overall duration of participation.

During treatment, the study team will review diary completion, concomitant medication and participants' health. Participants will also complete questionnaires and provide blood samples at scheduled visits.

The final follow-up assessment will take place approximately one month after the last treatment visit. It will include review of the final diary entries, medication use and any ongoing medical problems.

Enrollment: 250 estimated patients

Sex: All

Ages: 12 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subjects who have signed and dated Informed Consent Form (ICF).

2. Female or male aged 12 to 65 years, both included.

3. Subjects with confirmed clinical history of inhalation allergy with moderate-severe persistent rhinitis/ rhinoconjunctivitis according to the ARIA classification(1) of at least 1 year duration (treated with anti-allergic medication) with or without mild-moderate intermittent or persistent controlled asthma according to the definition of GINA 2023(2) caused by D. pteronyssinus and/or D. farinae. The asthma diagnosis will be valid up to 12 months prior to signing the informed consent.

4. Subjects with positive skin prick test to a standardized allergen extract of D. pteronyssinus and/or D. farinae. The wheal major diameter must be ≥ 5 mm and greater than or equal to the wheal major diameter of the positive control (histamine). The results will be valid up to 12 months prior to the signature of the informed consent.

5. Subjects 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. The results will be valid up to 12 months prior to the signature of the informed consent.

6. Subjects shall preferably be monosensitised to the study allergens. In the case of subjects sensitised to other aeroallergens, only those with the following characteristics (results valid 12 months prior to signing the informed consent form) may be included in the study:

   1. Subjects with a positive skin prick test for Blomia tropicalis, and/or Lepidoglyphus destructor and/or other mites. The specific IgE value for these allergens must be ≤ 3.5 kU/L.
   2. Subjects with positive skin prick test for dander may be included, provided that they have occasional exposure and symptoms. Subjects with habitual exposure to dander or living with animals must have a negative prick test.
   3. Subjects sensitised (positive prick test) to one or more pollens who must carry out the first symptom and medication collection (after baseline visit (BV) or additional baseline visit (ABV)) and last symptom and medication collection period (after visit 12), according to the following conditions:

1. Both symptom and medication collection periods must be carried out outside the pollen season.

2. Both symptom and medication collection periods must start at least one month before and one month after the pollen season.

An individual assessment of each subject will be performed in conjunction with the pollen calendar established for each geographical region to check that symptom and medication collection can be carried out under the above conditions. If this is not possible, subjects cannot be included in the study.

7. Subjects with negative skin prick test for moulds. 8. 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 confirm menarche and have a urine pregnancy test negative result before enrolling the study.

9. Women of childbearing age must commit to using a highly effective contraception method during the trial and up to 1 months after the end of the investigational medicinal product. Such methods include combined (estrogen and progestogen containing) hormonal, contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), male condom, diaphragm used with spermicide, bilateral tubal occlusion, vasectomised partner, or sexual abstinence.

10. Subjects capable of complying with dosage regimen. 11. Subjects must record symptoms and medication consumption in an electronic diary via smartphone (preferably) or in a paper diary.

To be confirmed at visit 1 (V1)

Only subjects who meet the following criteria will be eligible for randomization:

12. Subjects with a rhinitis/rhinoconjunctivitis combined symptom and medication score (RCSMS) ≥ 2 out of 6, recorded for at least 10 days, corresponding to moderate-to-severe allergic rhinitis/rhinoconjunctivitis (See Section 6.2).

Exclusion criteria

1. Subjects sensitised (positive prick test) to one or more pollens where the time interval between baseline visit (BV) and additional baseline visit (ABV) is more than 7 months.
2. Subjects who have received previous immunotherapy to allergens under study (D. pteronyssinus and D. farinae) during the last 5 years or currently receiving immunotherapy with any other allergen.
3. Subjects who have undergone any desensitisation process (e.g., oral immunotherapy [OIT], milk, or egg) except those in the maintenance phase since at least 12 months.
4. 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)
5. Subjects with uncontrolled asthma, according to GINA 2023(2),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.
6. Asthmatic subjects with forced expiratory volume in the first second (FEV1) <80% despite pharmacological treatment. The result shall be valid up to 12 months prior to signing of informed consent (See Section 9.2).
7. Subjects with severe asthma, according to GINA 2023(2), on Step 4 or 5 treatment, who had poor symptom control and had good adherence and inhaler technique.
8. Subjects on treatment with β-blockers, except those administered topically, or angiotensin-converting enzyme (ACE) inhibitors.
9. Subjects on treatment with immunosuppressive (not including corticosteroids), except those administered topically, or biological drug.
10. Subjects requiring regular treatment with systemic corticosteroids (oral or injectable) for the treatment of rhinitis/rhinoconjunctivitis and asthma. The regular use of topical, cutaneous, or inhaled corticosteroids for the treatment of the pathologies mentioned above and atopic dermatitis is permitted.
11. Unstable subjects who have suffered a respiratory tract infection and/or asthma exacerbation within 4 weeks prior to the screening/baseline visit.
12. Subjects who have suffered chronic urticaria, severe anaphylaxis, or family history of angioedema within 2 years prior to the screening/baseline visit.
13. Subjects having any contraindication for the use of adrenaline (e.g., hyperthyroidism, heart disease, or hypertension) according to the investigator's criteria.
14. Subjects with other severe disease not related asthma or rhinitis/rhinoconjunctivitis that could interfere in the study treatment or the follow-up (e.g., epilepsy or nephropathy) according to investigator's criteria.
15. Subjects with uncontrolled autoimmune diseases (e.g., thyroiditis or lupus), tumoral diseases, or immunodeficiencies.
16. Subjects that could not comply with the study protocol, according to investigator's criteria, or have a serious mental illness.
17. Subjects with known allergy to any of the components of the investigational medicinal products (IMPs) other than study allergens.
18. Subjects with lower respiratory tract diseases, different from asthma, as emphysema, bronchiectasis, or chronic obstructive pulmonary disease.
19. Use of drugs that could interfere with skin prick test reactions (e.g., antihistamines) within the deadlines set out in the protocol (See Section 9.2).
20. Subjects having any nasal condition (e.g., nasal polyp or non-allergic rhinitis) that could affect an appropriate evaluation of the efficacy and/or safety, according to investigator's criteria.
21. Subjects who required regular treatment with antihistamines and/or corticosteroids (systemic - oral or injectable-, topical, cutaneous, or inhaled) for other purposes than alleviating symptoms of allergic rhinitis, except temporal use (≤ 15 days) for diseases including common colds.
22. Breastfeeding or pregnant women.
23. Subjects who are immediate family members of the investigator.
24. Concurrent participation in other clinical trials or previous participation within 30 days prior to the screening/baseline visit.
25. Subjects with history of serious systemic reactions, including food, Hymenoptera venom, drugs, etc.
26. Subjects with controlled or uncontrolled cancer.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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250 participants in 2 patient groups, including a placebo group

mixture of Dermatophagoides (group 1)

Experimental group

Description:

Group 1 will receive subcutaneous EP-088-MM09 at a concentration of 3,000 mTU/mL.

Treatment:

Biological: EP-088_MM09

Placebo (group 2)

Placebo Comparator group

Description:

Group 2: will receive subcutaneous placebo, identical in composition to the active IMP, but without active ingredients.

Treatment:

Biological: Placebo