Clinical trial to assess the efficacy and safety of a vaccine for olive pollen allergy

Prior treatment

• Participation in another clinical trial or participation in a clinical trial within 30 days prior to enrolment,
• Uncontrolled asthma according to GINA 2026(2), including: • Poor symptom control (frequent symptoms, reliever use, activity limitation, or nocturnal symptoms), and/or • Frequent exacerbations (≥2/year requiring oral corticosteroids), or • Severe exacerbations (≥1/year requiring hospitalization).
• FEV1 < 80% of predicted despite appropriate pharmacological treatment (valid within 12 months prior to informed consent).
• Present clinical symptoms of upper or lower respiratory tract infection in the last two weeks before screening visit (Scr) or first treatment visit (T1) and/or exacerbation of obstructive or restrictive ventilation disorders within 4 weeks before Scr or T1 visits.
• Previous allergen immunotherapy with olive pollen allergens within the last 5 years.,
• Use of systemic immunosuppressive medications (e.g., methotrexate or cyclosporine A) or blood transfusion within 1 month prior to Screening
• Treatment with biologics (e.g., monoclonal antibodies), mast cell stabilisers, or anti-leukotriene agents
• Use of beta-blockers or ACE inhibitors
• Use of antidepressant/antipsychotic drugs with strong antihistaminic properties (e.g., tricyclic antidepressants).
• Use of systemic or nasal corticosteroids or antihistamines within the defined wash-out period prior to Screening (except maintenance asthma treatment)
• Ongoing allergen immunotherapy with any allergen,

Other illness

• Known hypersensitivity to the investigational medicinal product (IMP) excipients or placebo
• Clinically significant renal or chronic hepatic disease
• Active malignant disease (ongoing or within the past 5 years),
• Severe autoimmune disease
• Immunodeficiency, immunosuppression, or immunopathological conditions
• Severe uncontrolled chronic diseases (e.g., congestive heart failure, cardiovascular insufficiency, active gastric ulcer, inflammatory bowel disease, uncontrolled diabetes mellitus).
• Active tuberculosis
• Known positive serology for HIV-1/2, hepatitis B, or hepatitis C.
• Clinically relevant allergic rhinitis/rhinoconjunctivitis due to other environmental allergens during the observation period,
• Participants considered unlikely to comply with the protocol (e.g., substance abuse, serious psychiatric disorders, or unwillingness to comply with study requirements),
• History of severe systemic allergic reactions (Grade III–IV) and/or anaphylaxis (e.g., to food, Hymenoptera venom, or medications),

Lab values

• Clinically significant abnormal renal or hepatic laboratory values at Screening. Retesting is allowed once (≥7 days later); persistent abnormalities lead to exclusion.

Other

• Severe asthma according to GINA 2026, or asthma requiring GINA 2026 Step 4 or Step 5 treatment (2).
• Any contraindication to adrenaline (epinephrine), including hyperthyroidism
• Pregnant or breastfeeding women, or women of childbearing potential not using highly effective contraception
• Missing measurement of olive pollen-specific IgE
• Sensitisation to house dust mites with specific IgE ≥ 3.5 kU/L.
• Sensitisation to animal epithelia/dander with relevant exposure.
• Sensitisation to Alternaria alternata with specific IgE ≥ 3.5 kU/L.
• Grass pollen sensitisation, determined by molecular diagnosis, when specific IgE to the major grass pollen components (Phl p 1 and/or Phl p 5) is ≥ 0.30 kUA/L.
• Any relationship of dependence with the sponsor, or Investigator
• Inability to understand study procedures or trial documents
• Participants institutionalised by judicial or administrative order,

• Participants aged 12 to 64 years (inclusive).
• Participants whose rhinitis/rhinoconjunctivitis symptoms required regular treatment with intranasal corticosteroids, with or without H1-antihistamines, during the previous olive pollen season, corresponding to an RCSMS ≥ 2 (0–6 scale), according to the scoring system described by Pfaar et al.(1)
• Signed and dated Informed Consent Form by a legally competent participant,
• Good general physical and mental health, as determined by the Investigator,
• Diagnosis of olive pollen (Olea europaea) allergy, based on all of the following criteria: a. A Medical history of moderate-to-severe allergic rhinitis or rhinoconjunctivitis due to olive pollen allergens during at least the two previous consecutive olive pollen seasons, with clinically relevant symptoms during the olive pollen season according to the ARIA severity definition(3)), b. Treatment with anti-allergic medication for at least two olive pollen seasons prior to study inclusion, c. Positive skin prick test (SPT - wheal diameter ≥5 mm) to olive pollen allergens, with a positive control (histamine) wheal ≥5 mm (results valid 12 months prior to signing the informed consent form),
• Female participants: a. Women of childbearing potential (WOCBP: a woman is considered of childbearing potential according to the CTFG, if she is i.e., fertile, following menarche and until becoming postmenopausal unless becoming permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must be willing to use a highly effective method of contraception:Oral, intravaginal or transdermal hormonal medical drugs or -devices containing oestrogen/progesterone combinations. ii. Oral, injectable or implantable hormonal medical drugs or -devices containing progesterone-only. iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing system (IUS). v. Bilateral tubal occlusion. vi. Vasectomized partner (provided, that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success). b. Women not of childbearing potential (i.e., pre-menarche, tubal ligation, hysterectomy, or post-menopausal (a postmenopausal state is defined as no menses for 12 months without an alternative medical cause.)),
• For participants with asthma: a confirmed diagnosis of controlled mild-to-moderate asthma according to the Global Initiative for Asthma (GINA) guidelines (Steps 1–3, GINA 2026(2)). The diagnosis of asthma will be considered valid if established within 12 months prior to signing the informed consent form.
• For participants with obstructive or restrictive ventilation disorders (e.g., bronchial asthma, COPD, bronchial hyperreactivity): FEV1 ≥80% of the participant’s reference value or Peak Expiratory Flow (PEF) ≥80% of the participants´ individual optimal value,
• Laboratory assessments: a. Confirmed normal renal and liver function, including non-safety-related, non-clinically significant deviations outside the reference ranges. Participants with clinically significant deviations must be retested or excluded. Upon normalisation (being non-clinically significant) of the out-of-range value(s), the participant will be eligible. b. Specific IgE against olive pollen allergens (Olea europaea) with a value ≥ 3.5 KU/L. The results will be valid for up to 12 months prior to signing the informed consent form. c. Negative pregnancy test in blood at the screening visit for female participants of childbearing potential. The pregnancy test must be confirmed by a urine test at Visit T1.
• Participants shall preferably be monosensitised to the study allergen. In the case of participants 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: a. Participants with a positive skin prick test for Dermatophagoides or other house dust mites. The specific IgE value for these allergens must be < 3.5 kU/L. b. Participants with positive skin prick test for animal dander may be included, provided that they have occasional exposure and symptoms. Participants with habitual exposure to dander or living with animals must have a negative prick test. c. Participants sensitised (positive skin prick test) to other pollens may only be included if the corresponding pollen season does not coincide with the observation period (O1, O2, EoT). Participants with a positive skin prick test to grass pollen may only be included if the absence of molecular sensitisation to the major grass pollen components, Phl p 1 and Phl p 5, is confirmed, defined as specific IgE < 0.30 kUA/L for both components, as determined by a validated assay. d. Participants with positive skin prick test for Alternaria alternata. The specific IgE value must be < 3.5 kU/L.