Allergenic extract of grass pollen mixture: Dactylis glomerata, Festuca pratensis, Lolium perenne, Phleum pratense and Poa pratensis (1:1:1:1:1), polymerised for Allergic rhinoconjunctivitis (grass pollen-induced)|Seasonal allergy|Asthma (controlled, comorbidity)

Inclusion criteria

• {"criterion_text":"- 1.\tSigned and dated Informed Consent Form a. by a legally competent participant,\n- 2.\tPatients (males or females) aged from 18 to 65 years\n- 3.\tBeing in good physical and mental health\n- 4.\tConfirmed normal renal and liver function, including non-clinically significant deviations outside the reference ranges (< grade 2 according to the FDA Guidance for Industry for preventive Vaccine Trials [FDA 2007] at screening visit. Upon normalization of the out-of-range value(s), the participant will be eligible),\n- 5.\tFemales with childbearing potential (a woman is considered of childbearing potential [WOCBP] according to the CTFG, if she is i.e., fertile, following menarche and until becoming postmenopausal unless becoming permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must be willing to use a highly effective method of contraception: a.\tOral, intravaginal or transdermal hormonal medical drugs or -devices containing estrogen/progesterone combinations. b.\tOral, injectable or implantable hormonal medical drugs or -devices containing progesterone-only. c.\tIntrauterine device (IUD); d.\tIntrauterine hormone-releasing system (IUS) e.\tBilateral tubal occlusion f.\tVasectomized partner (provided that partner is the sole sexual partner of the WOCB trial participant and that the vasectomized partner has received medical assessment of the surgical success) g.\tBarrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository It should always be supplemented with the use of a spermicide. h.\tSexual abstinence (Defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant). or females unable to bear children (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.),\n- 6.\tFemale participants with childbearing potential must have a negative pregnancy test in serum at visit 1 (before randomization),\n- 7.\tHaving the diagnosis of grass pollen allergy based on all the following criteria: a.\tA medical history of allergic rhinoconjunctivitis for grass pollen allergens for at least the previous two pollen seasons, b.\tA medical history of moderate to severe rhinitis for grass pollen allergens for at least the previous two pollen seasons (definition of allergy severity according to ARIA, see Figure 2, c.\tA positive skin prick test (Beltaprick Test®, SPT - wheal diameter ≥3 mm) to grass pollen allergens, positive control (histamine) wheal ≥3 mm, negative control (NaCl) wheal <2 mm, d.\tSpecific IgE against grass pollen allergens in serum (minimum CAP class 3 or higher, ≥3.5 kU/L), e.\tPhl p1 and/or Phl p5 specific IgE in serum ≥ 3,5 kU/l, f.\tA positive CPT at the visit 1, meaning a Total Symptom Score (TSS) ≥ 5 (adjusted with respect to the reference eye), g.\tBeing treated with anti-allergic medication for at least the previous pollen season prior to enrolment\n- 8.\tFor asthmatic participants: confirmed diagnosis of controlled asthma during the treatment period according to Global Initiative for Asthma (GINA) guidelines (steps 1-3, GINA 2023),\n- 9.\tFEV1 ≥80% of the participant’s reference value or Peak Expiratory Flow (PEF) ≥80% of the participants´ individual optimal value (for asthmatic participants only)."}

Exclusion criteria

• {"criterion_text":"- 1.\tSimultaneous participation in other clinical trials or previous participation within 30 days before inclusion,\n- 10.\tMild persistent to severe persistent asthma partly controlled or uncontrolled asthma according to GINA guidelines (GINA 2023, (26))\n- 11.\tChronic asthma or emphysema, particularly with a forced expiratory volume in 1 second (FEV1) <80% of the participant’s reference value (ECSC) or Peak Expiratory Flow (PEF) <80% of the participants’ individual optimal value,\n- 12.\tHistory of a respiratory tract infection and/or exacerbation of asthma within 2 weeks before the screening\n- 13.\tHistory of significant renal disease or chronic hepatic disease,\n- 14.\tMalignant active disease (ongoing or within the five past years),\n- 15.\tSevere autoimmune disease,\n- 16.\tImmune defects including immunosuppression, immunopathies,\n- 17.\tVaccination during the entire treatment period, except flu and SARS-CoV-2 vaccinations,\n- 18.\tUse of systemic immunosuppressive medications (e.g., methotrexate or cyclosporine A) or blood transfusion from one month before screening until the end of the trial,\n- 19.\tGeneral inflammatory, severe acute or chronic inflammatory diseases,\n- 2.\tPrevious immunotherapy with grass pollen allergens within the last 5 years,\n- 20.\tOther chronic diseases such as severe congestive heart failure, cardiovascular insufficiency, active gastric ulcer, inflammatory bowel disease, uncontrolled diabetes mellitus, etc.,\n- 21.\tIntake of antidepressant drugs with potent antihistamine properties such as tricyclic antidepressants (e.g., doxepin, amitriptyline, desipramine, imipramine, etc.),\n- 22.\tAdministration or planned administration of anti-IgE antibodies, mast cell stabilizers or anti-leukotriene agents,\n- 23.\tIntake of beta-blockers,\n- 24.\tActive tuberculosis,\n- 25.\tHaving any contraindication for the use of adrenaline (including hyperthyroidism),\n- 26.\tKnown positive serology to Human Immunodeficiency Virus-1/2, Hepatitis B Virus or Hepatitis C Virus,\n- 27.\tFemales who are pregnant, lactating, or of child-bearing potential and not using a highly effective contraceptive method,\n- 28.\tAdministration of corticosteroids (systemic or nasal) or of anti-histaminic drugs before the screening visit (V0), as defined in the Table 6: Waiting period for screening; exception made for routine (previously prescribed) control medication for asthmatic participants,\n- 29.\tClinically relevant laboratory values, i.e., grade ≥2 according to the FDA Guidance for Industry for preventive Vaccine Trials (FDA 2007) at screening visit. Upon normalization of the out-of-range value(s) participant will be eligible,\n- 3.\tOngoing immunotherapy with grass pollen allergens or any other allergens,\n- 30.\tParticipants for who the Investigator believes will not comply with the study protocol (participants with known alcohol or drug abuse or with a history of a serious psychiatric disorder as well as participants unwilling to give informed consent or to abide by the requirements of the protocol).\n- 31.\tParticipants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.\n- 32.\tOcular disorders, such as inflammation/infection of the conjunctiva, cornea, or iris and in case of severe dry eye syndrome.\n- 33.\tAny type of eye surgery in the last 6 months.\n- 34.\tOcular surface diseases in which IgE-mediated hypersensitivity is not involved: Sjögren’s syndrome, blepharitis, blepharoconjunctivitis, urban ocular allergy syndrome, dry eye syndrome, giant papillary conjunctivitis after intolerance to contact lenses or foreign bodies.\n- 4.\tParticipants with acute allergic rhinitis/rhinoconjunctivitis due to other environmental allergens during the CPT performance,\n- 5.\tParticipants with a sensitization to other environmental allergens (i.e., other pollens, house dust mites, cat dander, dog dander or other perennial antigens) when they present relevant symptoms that can interferes the CPT performance,\n- 6.\tBeing in any relationship or dependence with the Sponsor, CRO and/or Investigator\n- 7.\tInability to understand instructions/study documents,\n- 8.\tHistory of severe systemic reactions and/or anaphylaxis, including food (e.g., peanut, marine animals) or to Hymenoptera venom (e.g., bee, wasp stings) or to medication (e.g., penicillin), etc.,\n- 9.\tHistory of hypersensitivity to the excipients of the investigational product or placebo"}

Primary endpoints

• {"endpoint_text":"- Proportion of patients whose reactivity to the Conjunctival Provocation Test (CPT) with grass extract decreases between baseline and visit 7. It means that the titrated 10 – fold step allergen concentration required to develop a positive response is at least one dose higher","definition_or_measurement_approach":"Measured by Conjunctival Provocation Test (CPT): decrease in reactivity defined as the titrated 10‑fold step allergen concentration required to develop a positive response being at least one dose higher between baseline (V0) and visit 7 (V7)."}

Secondary endpoints

• {"endpoint_text":"- Serum values of total IgE, grass specific IgE and IgG4 at baseline and final visit. Serum Phl p1 and Phl p5 specific IgE and IgG4 values at baseline and final visit (V0 and V7).","definition_or_measurement_approach":"Serum measurements of total IgE, grass-specific IgE, IgG4, and specific Phl p1/Phl p5 IgE and IgG4 at baseline (V0) and final visit (V7)."}

Spain

Earliest CTIS Part Ii Submission Date

08-04-2025

Latest Decision Or Authorization Date

09-06-2025

Processing Time Days

62

Number Of Sites

10

Number Of Participants

80

Poland

Earliest CTIS Part Ii Submission Date

28-05-2025

Latest Decision Or Authorization Date

16-06-2025

Processing Time Days

19

Number Of Sites

6

Number Of Participants

40

Primary sponsor

Full Name

Probelte Pharma S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain