GRASS POLLEN ALLERGEN EXTRACT MODIFIED WITH GLUTARALDEHYDE AND ADSORBED TO L-TYROSINE for Seasonal allergic rhinitis | Allergic rhinoconjunctivitis induced by grass pollen

Inclusion criteria

• {"criterion_text":"-1. Written informed consent from a legal representative on the subject’s behalf (with/without assent depending on applicable country-specific regulations).\n-10. Forced expiratory volume in 1 second (FEV1) ≥80% of predicted and FEV1/forced vital capacity (FVC) ≥75% or, if adequate spirometry cannot be performed, PEFR ≥75% predicted at screening and randomisation visit.\n-11. Be able to adhere to dose and visit schedule\n-2. Subjects aged 4 to 16 years inclusive at the time of signing the consent (assent) form. The subject must be ≥5 to ≤16 years old at the first randomisation visit.\n-3. Male or female.\n-4. Female subjects are allowed to participate in the trial if: i. Not of childbearing potential (defined as premenarche). ii. Of childbearing potential with a negative urine pregnancy test at all visits and, if sexually active, agree to use 1 highly effective method of contraception, during the whole duration of the trial, starting at least 7 days before first dose administration and for at least 30 days after the last dose of IMP/placebo or after next menstruation, whichever is longer.\n-5. Good general health, as determined by the Investigator based on a medical evaluation including medical history, physical examination and laboratory tests. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the trial procedures.\n-6. Positive history of moderate to severe SAR ascribed to grass (Pooideae) pollen exposure, of at least one year duration or by the 5th birthday (for children of 5-6 years old), with moderate to severe SAR symptoms despite having received allergy pharmacotherapy.\n-7. A positive skin prick test (SPT) to grass pollen (wheals [longest diameter] ≥ 3 mm and histamine ≥ 3 mm) and a negative SPT to the negative control (wheal diameter = 0 mm) at screening.\n-8. Grass specific IgE class ≥2 as documented by an immunoCAP test at screening. (Please note: Class ≥2 by an ImmunoCAP test implies grass specific IgE ≥0.71 kUA/L)\n-9. Children who are able to perform spirometry or peak flow measurements."}

Exclusion criteria

• {"criterion_text":"-1. Pregnant or lactating subject.\n-10. Presence of any acute or chronic ocular disorder, other than allergic conjunctivitis.\n-11. Presence of any skin conditions (e.g., skin abnormalities, tattoos etc.), which might interfere with the interpretation of the SPT results.\n-12. Severe eczema with involvement of more than 25% of the body surface.\n-13. Clinical history of Type I diabetes. Subjects with well-controlled Type II diabetes will be allowed to participate at the discretion of the Investigator.\n-14. Any acute infection (including upper respiratory tract infections in the 7 days prior to Visit 2, which in the opinion of the investigator may pose a safety risk to the subject.\n-15. Clinical history of severe or life-threatening anaphylactic reactions to foods, insect venom, exercise, drugs or idiopathic anaphylaxis\n-16. Clinical history of allergy, hypersensitivity or intolerance to the excipients of the trial medication.\n-17. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.\n-18. History of any previous allergen immunotherapy, by any route.\n-19. Unable to meet medication washout requirements listed in the table prohibited medications.\n-2. Presence of any medical history of moderate to severe allergy symptoms, to any other seasonal allergen (other than grass) or perennial allergens, confirmed by a positive specific IgE [Class ≥2] at screening.\n-20. Unable to receive epinephrine therapy or at greater risk of developing adverse reactions after epinephrine administration as assessed by the Investigator.\n-21. Monoamine oxidase inhibitor medication and tricyclic antidepressants.\n-22. Β-blocker medication for any indication.\n-23. Any previous therapy (within the previous 5 years) or current therapy with anti-IgE (e.g., Xolair), anti-interleukins (ILs) (e.g., mepolizumab) or any other therapy with a biologic agent.\n-24. All vaccinations (including influenza and coronavirus disease 2019 [COVID-19] vaccines, and treatment with a preparation containing MPL [e.g., Cervarix, Fendrix]) administered 30 days or less prior to randomisation or any planned vaccinations during the treatment periods. Influenza and other vaccinations should also be avoided for 30 days after the last injection of every treatment period. Emergency vaccinations (e.g., tetanus due to injury) can be administered at any time.\n-25. Participation in a clinical trial research trial with any IMP within 4 weeks from screening.\n-26. Known fear of injections that in the opinion of the Investigator, may impact adherence to the dosing schedule and cooperation with required clinical trial procedures.\n-27. Clinical history of drug or alcohol abuse which, in the Investigator’s opinion, could interfere with the subject’s ability to participate in the trial.\n-28. Personal, financial or other dependent relationship (e.g., employee or immediate relative) with the trial site, Sponsor, Sponsor’s representative, or another individual who has access to the clinical trial protocol.\n-29. Vulnerable subjects or those in judicial or governmental detention, detainment or imprisonment in a public institution, except children in long-term foster care, at the discretion of the Investigator.\n-3. Moderate to severe symptoms during the 2 years prior to screening to a perennial or seasonal allergen not tested by IgE (for Exclusion Criterion #2), that cannot be avoided during the trial and the symptoms of which may interfere with administration of treatment and/or impact the data collected, as determined by the Investigator.\n-4. Presence of any medical condition that may reduce the ability to survive a serious allergic reaction.\n-5. History of any autoimmune disease or other immunological disorder or other diseases (including, but not limited to malignancy, cardiovascular, gastro-intestinal, hepatic, renal, haematological, neurological, psychiatric, endocrine or pulmonary disease) that in the opinion of the Investigator may pose a safety risk or compromise the interpretation of efficacy of the trial treatment.\n-6. Presence of severe or poorly controlled asthma as defined by current Global Initiative for Asthma (GINA) guidelines (current GINA) or requiring more than a daily dose above 800 μg (in adolescents) or 400 μg (in children) of inhaled budesonide [or equivalent inhaled corticosteroid].\n-7. Hospital admission for exacerbation of asthma in the 12 months prior to Visit 1 or any history of a life-threatening asthma attack.\n-8. Presence of non-atopic rhinitis and/or rhino-sinusitis (with or without polyps).\n-9. Presence of nasal polyps and/or chronic sinusitis."}

Primary endpoints

• {"endpoint_text":"-Part A: The CSMS averaged over the peak GPS during Year 1.","definition_or_measurement_approach":"CSMS = Combined Symptom and Medication Score averaged over the peak grass pollen season (peak GPS) in Year 1."}
• {"endpoint_text":"-Part B: The CSMS averaged over the peak GPS after 2 years of treatment-free follow-up.","definition_or_measurement_approach":"CSMS = Combined Symptom and Medication Score averaged over the peak grass pollen season (peak GPS) after 2 years of treatment-free follow-up."}

Secondary endpoints

• {"endpoint_text":"Part A Efficacy: - The CSMS averaged over the entire (or truncated) GPS. - The dSS component of the CSMS averaged over the peak GPS. - The dMS component of the CSMS averaged over the peak GPS.","definition_or_measurement_approach":"CSMS and its components (daily Symptom Score dSS and daily Medication Score dMS) averaged over entire or peak grass pollen season (GPS) as specified."}
• {"endpoint_text":"- The TCS averaged over the peak GPS. - The probability of well days and severe days during the peak GPS. - Serum grass specific IgG4 at Visit 11 compared to Part A Visit 1 (baseline). - Change from Part A Visit 2 (baseline) to Visit 11 in PRQLQ, AdolRQLQ and RQLQ(S) measured in selected countries.","definition_or_measurement_approach":"TCS = Total Combined Score averaged over peak GPS; well days/severe days probability calculated over peak GPS; serum grass-specific IgG4 measured by laboratory assay; quality-of-life instruments PRQLQ, AdolRQLQ, RQLQ(S) compared to baseline visits."}
• {"endpoint_text":"Part A Safety: - Frequency, severity and relationship of AEs to treatment. - Frequency of AEs leading to premature discontinuation from treatment or trial. - Frequency of AESI.","definition_or_measurement_approach":"Standard safety reporting: adverse event (AE) frequency, severity, relationship to IMP, AEs leading to discontinuation, adverse events of special interest (AESI)."}
• {"endpoint_text":"- Changes in clinical laboratory values (serum chemistry, haematology, urinalysis) between screening and Visit 11. - Changes in vital signs (all subjects) and spirometry/PEFR (only in subjects with past or current asthma) at all treatment visits.","definition_or_measurement_approach":"Laboratory parameters compared between screening and Visit 11; vital signs and lung function (spirometry/PEFR) measured at treatment visits."}
• {"endpoint_text":"Part B Efficacy: Key secondary: -To evaluate the long-term efficacy of PQ Grass. -To evaluate IgG4 after 3 years of treatment.","definition_or_measurement_approach":"Long-term efficacy assessed by CSMS/TCS and immunologic marker IgG4 measured after 3 years of treatment."}
• {"endpoint_text":"- The CSMS averaged over the entire (or truncated) GPS after 3 years of treatment. - The dSS component of the CSMS averaged over the peak GPS after 2 years of treatment-free follow-up. - The dMS component of the CSMS averaged over the peak GPS after 2 years of treatment-free follow-up. - Serum grass specific IgG4 after 3 years of treatment compared to Part B Visit 1 (baseline).","definition_or_measurement_approach":"CSMS/dSS/dMS averaged over GPS at specified timepoints; serum IgG4 compared to baseline."}
• {"endpoint_text":"Part B Efficacy: Other secondary: -To evaluate the yearly efficacy of PQ Grass during the GPS. -To evaluate the efficacy of PQ Grass on the dSS and dMS components of the CSMS during the peak GPS. -To evaluate well days and severe days during the GPS. -To evaluate grass specific IgG4 after 1 and 2 years of treatment. -To evaluate the quality of life.","definition_or_measurement_approach":"Yearly CSMS analyses over GPS; component scores dSS/dMS; well/severe day probabilities; serum IgG4 at years 1 and 2; QoL measures."}
• {"endpoint_text":"- The dSS component of the CSMS averaged over the peak GPS after 1, 2 and 3 years of treatment and 1 and 2 years of treatment-free follow-up. - The dMS component of the CSMS averaged over the peak GPS after 1, 2 and 3 years of treatment and 1 and 2 years of treatment-free follow-up. - The probability of well days and severe days during the peak GPS after 1, 2 and 3 years of treatment and 1 and 2 years of treatment-free follow-up.","definition_or_measurement_approach":"dSS and dMS averaged over peak GPS at multiple treatment and follow-up timepoints; probabilities of well/severe days assessed."}
• {"endpoint_text":"- Serum grass specific IgG4 after 1 and 2 years of treatment compared to Part B Visit 1 (baseline). - Changes from Part B Visit 2 (baseline) in RQLQ(S), PRQLQ and AdolRQLQ measured in selected countries, after 1, 2 and 3 years of treatment and 1 and 2 years of treatment-free follow-up.","definition_or_measurement_approach":"Serum IgG4 measured and compared to baseline; quality-of-life questionnaires compared to baseline at specified timepoints."}
• {"endpoint_text":"Part B Safety: - Frequency, severity and relationship of AEs to treatment. - Frequency of AEs leading to premature discontinuation from treatment or trial. - Frequency of AESI.","definition_or_measurement_approach":"Safety reporting analogous to Part A over long-term treatment and follow-up."}
• {"endpoint_text":"- Changes in clinical laboratory values (serum chemistry, haematology, urinalysis). - Changes in vital signs (all subjects) and spirometry/PEFR (only in subjects with past or current asthma) at all treatment visits.","definition_or_measurement_approach":"Laboratory, vital sign and lung function monitoring across treatment visits."}
• {"endpoint_text":"- The CSMS averaged over the peak GPS after 3 years of treatment. - The TCS averaged over the peak GPS after 3 years of treatment. - The TCS averaged over the peak GPS after 2 years of treatment-free follow-up.","definition_or_measurement_approach":"CSMS and TCS averaged over peak GPS at 3 years and after treatment-free follow-up as specified."}

Methods

• Digital/social media advertising — documents labelled 'Digital Ad', 'SocialMediaText', 'Digital Advertisment' and 'AdvertisingCampaign' indicate use of social media and online digital adverts (country-specific digital adverts present for e.g., LT, RO, BG, EN).
• Landing page / online recruitment — 'LandingPageText' documents indicate a study-specific landing page for recruitment.
• GP / Dr-to-Dr letters — 'GP letter' and 'Dr to Dr Letter' recruitment materials indicate direct outreach to general practitioners/physicians to refer eligible subjects.
• Posters and flyers — 'Poster_Flyer' and 'Leaflet' materials indicate site-based printed recruitment materials.
• Site advertisement package / site advertisement — 'Site advertisement package' materials provided to sites.
• Participant incentive / small token of appreciation — 'Participant Incentive List' and 'Small Token of Appreciation Examples' indicate use of incentives.
• Subject motivation card / GrassPass — 'Subject motivation card_GrassPass' materials for subjects.
• Country-specific recruitment materials and quick reference guides — multiple country-associated K1/K2 materials (EN, DE, RO, PL, SK, BG, LT, CZ) indicate localised recruitment content and quick reference guides for sites.
• Data protection and consent for advertising — 'AdvertisingCampaign_DataProtectionConsent' and 'DataProtectionDeclarationWebsite' documents included with digital recruitment materials.

Slovakia

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

525

Number Of Participants

52

Poland

Earliest CTIS Part Ii Submission Date

27-05-2024

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

693

Number Of Participants

96

Romania

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

680

Number Of Participants

25

Lithuania

Earliest CTIS Part Ii Submission Date

28-05-2024

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

713

Number Of Participants

25

Germany

Earliest CTIS Part Ii Submission Date

09-05-2024

Latest Decision Or Authorization Date

11-03-2026

Processing Time Days

671

Number Of Participants

92

Czechia

Earliest CTIS Part Ii Submission Date

30-05-2024

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

656

Number Of Participants

32

Bulgaria

Earliest CTIS Part Ii Submission Date

21-05-2024

Latest Decision Or Authorization Date

14-05-2026

Processing Time Days

723

Number Of Participants

36

Primary sponsor

Full Name

Allergy Therapeutics (UK) Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Syneos Health Netherlands B.V.

Responsibilities

Sponsor duties codes listed (1, 12, 15 'site feasibility', 5, 8) — operational trial support/site feasibility as listed in record

Name

Syneos Health Romania S.R.L.

Responsibilities

Sponsor duties codes listed (1, 12, 15 'site feasibility', 5, 8) — operational trial support/site feasibility as listed in record

Name

Sharp Clinical Services (UK) Limited

Responsibilities

Labelling and packaging

Third parties

• {"country":"United Kingdom","full_name":"Sharp Clinical Services (UK) Limited","duties_or_roles":"Labelling and packaging","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Manufacturing Packaging Farmaca (MPF) B.V.","duties_or_roles":"Labelling and packaging","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Tools4Patient","duties_or_roles":"Sponsor duty code 7 (unspecified in record)","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Syneos Health Romania S.R.L.","duties_or_roles":"Sponsor duties codes: 1, 12, 15 (site feasibility), 5, 8 (as listed)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"SGS Analytics Germany GmbH","duties_or_roles":"Laboratory testing (code 4)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Imperial College London Limited","duties_or_roles":"Biomarker analysis","organisation_type":"Educational Institution"}
• {"country":"Austria","full_name":"AZ Pollen Research GmbH","duties_or_roles":"Pollen count data","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Qiagen GmbH","duties_or_roles":"Biomarker analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Medaimun GmbH","duties_or_roles":"Sponsor duty code 15 / Subject Recruitment / Advertisement (for Germany only) (listed duties include laboratory roles)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Cerba","duties_or_roles":"Laboratory testing (code 4)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"Electronic data capture / eCOA related duties (code 7 listed)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Metronomia Clinical Research GmbH","duties_or_roles":"Multiple sponsor duties (codes 10, 11, 3, 6) as listed","organisation_type":"Pharmaceutical company"}