Allergenic extract of grass pollen mixture (Dactylis glomerata, Festuca pratensis, Lolium perenne, Phleum pratense and Poa pratensis), polymerised for Allergic rhinoconjunctivitis (grass pollen allergy)|Seasonal allergy (grass pollen)

Inclusion criteria

• {"criterion_text":"- 1. Signed and dated Informed Consent Form a. by a legally competent participant,\n- 2. Patients (males or females) aged from 18 to 65 years,\n- Being in good physical and mental health,\n- 4. Confirmed 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. Participants with laboratory values > grade 1 will require retesting. Upon normalization of the out-of-range value(s), the participant will be eligible),\n- 5. Females 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. Oral, intravaginal or transdermal hormonal medical drugs or -devices containing oestrogen/progesterone combinations. b. Oral, injectable or implantable hormonal medical drugs or -devices containing progesterone-only. c. Intrauterine device (IUD); d. Intrauterine hormone-releasing system (IUS) e. Bilateral tubal occlusion f. Vasectomized 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. Barrier 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. Sexual 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. Female participants with childbearing potential must have a negative pregnancy test in serum at visit 1 (before randomization),\n- 7. Having the diagnosis of grass pollen allergy based on all the following criteria: a. A medical history of allergic rhinoconjunctivitis for grass pollen allergens for at least the previous two pollen seasons, b. A 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 Figureg. Being treated with anti-allergic medication for at least the previous pollen season prior to enrolment. 8. For asthmatic participants: confirmed diagnosis of controlled asthma during the treatment period according to Global Initiative for Asthma (GINA) guidelines (steps 1-3, GINA 2023), 9. FEV1 ≥80% of the participant’s reference value or Peak Expiratory Flow (PEF) ≥80% of the participants´ individual optimal value (for asthmatic participants only), 10. Willingness and ability to complete a PROGRASS Diary Patient App during the pollen season. 2, c. A 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. Specific IgE against grass pollen allergens in serum (minimum CAP class 3 or higher, ≥3.5 kU/L), e. Phl p1 and/or Phl p5 specific IgE in serum ≥ 3,5 kU/l, f. A positive CPT at the visit 1, meaning a Total Symptom Score (TSS) ≥ 5 (adjusted with respect to the reference eye),"}

Exclusion criteria

• {"criterion_text":"- 1. Simultaneous participation in other clinical trials or previous participation within 30 days before inclusion,\n- 2. Previous immunotherapy with grass pollen allergens within the last 5 years,\n- 3. Ongoing immunotherapy with grass pollen allergens or any other allergens,\n- 4. Participants with acute allergic rhinitis/rhinoconjunctivitis due to other environmental allergens during the study period,\n- 5. Participants 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 with grasses pollen season or the CPT performance,\n- 6. Being in any relationship or dependence with the Sponsor, CRO and/or Investigator,\n- 7. Inability to understand instructions/study documents,\n- 8. Participants who do not have access to a smartphone/tablet (iOS or Android, in exceptional cases, a paper diary may be issued if installation on the mobile device is not technically possible),\n- 9. History of severe systemic reactions and/or anaphylaxis, including to food (e.g., peanut, marine animals) or to Hymenoptera venom (e.g., bee, wasp stings) or to medication (e.g., penicillin), etc.,\n- 10. History of hypersensitivity to the excipients of the investigational product or placebo,\n- 11. Mild persistent to severe persistent asthma partly controlled or uncontrolled asthma according to GINA guidelines (GINA 2023, (26))\n- 12. Chronic 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- 13. History of a respiratory tract infection and/or exacerbation of asthma within 2 weeks before the screening,\n- 14. History of significant renal disease or chronic hepatic disease,\n- 15. Malignant active disease (ongoing or within the five past years),\n- 16. Severe autoimmune disease,\n- 17. Immune defects including immunosuppression, immunopathies,\n- 18. Vaccination during the entire treatment period, except flu and SARS-CoV-2 vaccinations,\n- 19. Use 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- 20. General inflammatory, severe acute or chronic inflammatory diseases,\n- 21. Other chronic diseases such as severe congestive heart failure, cardiovascular insufficiency, active gastric ulcer, inflammatory bowel disease, uncontrolled diabetes mellitus, etc.\n- 22. Intake of antidepressant drugs with potent antihistamine properties such as tricyclic antidepressants (e.g., doxepin, amitriptyline, desipramine, imipramine, etc.),\n- 23. Administration or planned administration of anti-IgE antibodies, mast cell stabilizers or anti-leukotriene agents,\n- 24. Intake of beta-blockers,\n- 25. Active tuberculosis,\n- 26. Having any contraindication for the use of adrenaline (including hyperthyroidism),\n- 27. Known positive serology to Human Immunodeficiency Virus-1/2, Hepatitis B Virus or Hepatitis C Virus,\n- 28. Females who are pregnant, lactating, or of child-bearing potential and not using a highly effective contraceptive method,\n- 29. Administration 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- 30. Clinically relevant laboratory values, i.e., grade ≥2 according to the FDA Guidance for Industry for preventive Vaccine Trials (FDA 2007) at screening visit (Participants with laboratory values > grade 1 will require retesting. Upon normalization of the out-of-range value(s), participant will be eligible),\n- 31. Participants 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- 32. Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.\n- 33. Ocular disorders, such as inflammation/infection of the conjunctiva, cornea, or iris and in case of severe dry eye syndrome.\n- 34. Any type of eye surgery in the last 6 months.\n- 35. Ocular 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."}

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":"Defined as the titrated 10‑fold step allergen concentration required to develop a positive CPT response being at least one dose higher between baseline and visit 7."}

Secondary endpoints

• {"endpoint_text":"- Combined nasal and conjunctival symptoms and rescue medication score (CSMS) obtained during the peak pollen season through the Diary patient App. Nasal and conjunctival symptoms score obtained during the peak pollen season through the Diary patient App.","definition_or_measurement_approach":"Measured using the Diary patient App during the peak pollen season (CSMS: combined symptoms and medication score)."}
• {"endpoint_text":"- Rhinoconjunctivitis daily medication score obtained during the peak pollen season through the Diary patient App.","definition_or_measurement_approach":"Measured via the Diary patient App during the peak pollen season (daily medication score for rhinoconjunctivitis)."}

Spain

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

10-06-2024

Processing Time Days

67

Number Of Sites

7

Number Of Participants

50

Poland

Earliest CTIS Part Ii Submission Date

28-05-2024

Latest Decision Or Authorization Date

14-06-2024

Processing Time Days

17

Number Of Sites

11

Number Of Participants

100

Primary sponsor

Full Name

Probelte Pharma S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain