PLACEBO for Seasonal allergic rhinitis | Allergic rhinoconjunctivitis

Inclusion criteria

• {"criterion_text":"- 1. Capable of giving signed informed consent as described in Appendix 1 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this clinical trial protocol and to attend required clinical trial visits.\n- 10. Birch-specific IgE class ≥2 (i.e., ≥0.71 kUA/L) as documented by an ImmunoCAP test at screening.\n- 11. Forced expiratory volume in one second (FEV1) ≥70% of predicted and PEFR ≥70% of predicted at screening.\n- 2. Subject who has a signed and dated ICF.\n- 3. Subject must be 18 to 65 years of age inclusive, at the time of signing the ICF.\n- 4. Male or female.\n- 5. For female subjects only: Female subjects who are not of childbearing potential (defined as at least 12 months natural spontaneous amenorrhoea, or at least 6 weeks following surgical menopause/permanent sterilisation [hysterectomy, bilateral oophorectomy and bilateral salpingectomy]) or females of childbearing potential who agree to comply with the contraceptive requirements of the clinical trial protocol.\n- 6. Good general health, as determined by the Investigator, based on a medical evaluation, including medical history, physical examination, mental status assessment 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 clinical trial procedures.\n- 7. Positive history of moderate to severe symptoms of SAR/rhinoconjunctivitis ascribed to birch pollen exposure of at least 2 seasons’ duration, despite having received allergy pharmacotherapy (e.g., antihistamines, nasal corticosteroids, leukotriene modifiers, etc.) during the last 2 consecutive birch pollen seasons prior to the clinical trial, confirmed by subject records.\n- 8. A positive SPT to histamine (wheals [longest diameter] ≥3 mm) and a negative SPT to the negative control (wheal diameter = 0 mm) at screening.\n- 9. A positive SPT for birch pollen (wheals [longest diameter] ≥3 mm)."}

Exclusion criteria

• {"criterion_text":"- 1. Pregnant or lactating subject.\n- 10.\tPresence of chronic rhino-sinusitis. Chronic rhino-sinusitis will be diagnosed when at least two of the following four symptoms are present and occur for more than 12 weeks: (1) purulent drainage, (2) facial and/or dental pain, (3) nasal obstruction, (4) hyposmia.\n- 11. Presence of nasal polyps.\n- 12. Eye surgery within the past 6 months.\n- 13. Presence of any skin conditions (e.g., skin abnormalities, tattoos etc.), which might interfere with the interpretation of the SPT results.\n- 14. Clinical history of Type I diabetes or poorly controlled Type II diabetes.\n- 15. Moderate to severe upper or lower respiratory infections requiring medication within 14 days before Visit 1.\n- 16. Presence of acute or chronic infection, fever or inflammation at Visit 1 or Visit 1a.\n- 17. Clinical history of serious systemic reaction in response to AIT in the past.\n- 18. Clinical history of life-threatening anaphylactic reactions to foods, insect venom, exercise, drugs or idiopathic anaphylaxis.\n- 19. Clinical history of allergy, hypersensitivity or intolerance to the excipients of the investigational drug/placebo.\n- 2. Presence of any medical history of moderate to severe allergy symptoms.\n- 20. Clinical history of allergy, hypersensitivity or intolerance to the relief medications (for relief of allergy symptoms during Period 3) provided for use in this clinical trial.\n- 21. Clinical history of hereditary angioedema.\n- 22. Clinical history of mast cell disorder including mastocytosis, chronic urticaria or urticaria pigmentosa.\n- 23. Unable to receive epinephrine therapy (i.e., use of epinephrine is contraindicated such as in subjects with hyperthyroidism, uncontrolled hypertension, cardiac arrhythmias, closed angle glaucoma or subjects taking other sympathomimetics).\n- 24. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.\n- 25. Clinical history of drug or alcohol abuse, which, in the Investigator’s opinion, could interfere with the subject’s ability to participate in the clinical trial.\n- 26. Any history of AIT of any type for birch or tree pollen allergy in the past (irrespective of how long ago this was).\n- 27. Any history of AIT of any type for any other type of allergy in the past 5 years. Exception: Subjects who received AIT in the past 5 years for food allergy are not excluded.\n- 28. Inability to adhere to the washout periods listed in Table 8 of the protocol, with respect to screening and to refrain from using the medications indicated until after Visit 12.\n- 29. Treatment with a preparation containing MPL (e.g., Cervarix, Shingrix, Fendrix) within 2 years prior to Visit 1 and until after completion of Visit 12 (with the exception of the investigational drug).\n- 3. Moderate to severe symptoms during the 3 years prior to Visit 1 to any other seasonal or perennial allergen not tested in the sIgE measurements done at screening that cannot be avoided during Period 1 to Period 3 of the clinical trial and the symptoms of which may interfere with administration of treatment and/or impact the data collected.\n- 30. Previous history of epinephrine auto-injector use.\n- 31. β-blocker medication (local or systemic, including eye drops) for any indication.\n- 32. Monoamine oxidase inhibitors and tricyclic antidepressants.\n- 33. Any previous therapy (within the previous 5 years) or current therapy with biologics such as e.g., anti-IgE (e.g., omalizumab [Xolair]) or anti-interleukins (e.g., mepolizumab).\n- 34. Current or past therapy (within the previous 5 years) with any other immunomodulatory therapies.\n- 35. Unable to refrain from any vaccination (including influenza vaccine) during the clinical trial (unless administered >30 days prior to randomisation).\n- 36. Participation in a clinical research trial with any investigational drug within 4 weeks of Visit 1 or concomitantly with this clinical trial.\n- 37. Personal, financial or other dependent relationship (e.g., employee or immediate relative) with the clinical trial site, Sponsor, Sponsor’s representative, or another individual who has access to the clinical trial protocol.\n- 38. Vulnerable subjects or those in judicial or governmental detention, detainment or imprisonment in a public institution.\n- 39. Subjects likely to have prolonged periods of absence from home to an area with dissimilar pollen burden during the BPS (e.g., business or private travel) of greater than 3 consecutive days in one week (Monday to Sunday) or a total of 7 days during BPS.\n- 4. Presence of any medical condition that may reduce the ability to survive a serious allergic reaction.\n- 40. Have changed residence to an area with dissimilar pollen burden (s) since the last BPS.\n- 5. Presence of active systemic autoimmune disorder, systemic autoimmune disorders in remission or active organ specific autoimmune disorder.\n- 6. Presence of active malignant neoplasia, severe cardiovascular disease (e.g., coronary artery disease, cardiac insufficiency, etc.), pulmonary insufficiency, severe psychiatric disorders or primary and secondary immunodeficiencies.\n- 7. History of any other immunological disorder or other diseases (including, but not limited to cardiovascular [including uncontrolled or inadequately controlled hypertension], gastro-intestinal, hepatic, renal, haematological, neurological, endocrine or pulmonary disease) that in the opinion of the Investigator may pose a safety risk or compromise the interpretation of efficacy of the clinical trial treatment.\n- 8. Presence of severe or poorly controlled or uncontrolled asthma as defined in the protocol.\n- 9. Presence of non-atopic rhinitis."}

Primary endpoints

• {"endpoint_text":"- CSMS averaged over the peak BPS.","definition_or_measurement_approach":"CSMS = combined symptom and medication score, measured and averaged over the peak birch pollen season (peak BPS)."}

Secondary endpoints

• {"endpoint_text":"- Secondary Efficacy: - CSMS averaged over the entire BPS. - The dSS component of the CSMS averaged over the peak BPS. - The dMS component of the CSMS averaged over the peak BPS. - The TCS averaged over the peak BPS. - CSMS averaged over the combined peak seasons for alder, hazel, birch and oak pollen season (peak TPS). - RQLQ(S) measured at Visit 11.","definition_or_measurement_approach":"Efficacy endpoints based on CSMS (combined symptom and medication score) averaged over specified pollen seasons (entire BPS, peak BPS, peak TPS); RQLQ(S) assessed at Visit 11."}
• {"endpoint_text":"- - Serum birch-specific IgG4 at pre-BPS (Visit 9) compared to baseline.","definition_or_measurement_approach":"Measurement of serum birch-specific IgG4 at pre-BPS (Visit 9) compared with baseline values."}
• {"endpoint_text":"- Safety: - Frequency, severity and relationship of AEs to treatment. - Frequency of AEs leading to premature discontinuation from treatment or clinical trial. - Changes in clinical laboratory values (serum chemistry, haematology and urinalysis) between screening and Visit 12. - Changes in vital signs at all treatment visits.","definition_or_measurement_approach":"Safety endpoints comprise AE reporting (frequency, severity, relationship), AEs causing discontinuation, laboratory value changes between screening and Visit 12 (serum chemistry, haematology, urinalysis), and changes in vital signs across treatment visits."}

Methods

• Site advertisement packages and study posters at participating centres.
• Web banners and social media advertisements (including Facebook) and landing pages.
• Advertisement videos (multiple videos) for digital outreach.
• Patient study leaflets and flyers (long and short formats) distributed at sites.
• Site-specific recruitment toolkits and patient letters (country/site specific: e.g., KliFo Dresden, Schwerin toolkits).
• Subject Recruitment / Advertisement outsourced to third parties (e.g., Probando GmbH noted for Subject Recruitment / Advertisement).

Austria

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

28-10-2024

Processing Time Days

21

Number Of Participants

34

Germany

Earliest CTIS Part Ii Submission Date

18-09-2024

Latest Decision Or Authorization Date

22-10-2024

Processing Time Days

34

Number Of Participants

295

Poland

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

28-10-2024

Processing Time Days

38

Number Of Participants

233

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

sponsorDuties codes: 1,12,15 (site feasibility),5,8; site feasibility and other operational duties; contact Info@syneoshealth.com

Name

Metronomia Clinical Research GmbH

Responsibilities

sponsorDuties codes: 10,11,3,6; operational/clinical support (codes as listed); contact info@metronomia.net

Third parties

• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"sponsorDuties codes: 1,12,15 (site feasibility),5,8; contact email: Info@syneoshealth.com","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Metronomia Clinical Research GmbH","duties_or_roles":"sponsorDuties codes: 10,11,3,6; contact email: info@metronomia.net","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Imperial College London Limited","duties_or_roles":"sponsorDuties code: 15 (Biomarker analysis); contact email: shamjilab@imperial.ac.uk","organisation_type":"Educational Institution"}
• {"country":"Germany","full_name":"SGS Analytics Germany GmbH","duties_or_roles":"sponsorDuties code: 4; contact email: de.hn.muc.info@sgs.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Manufacturing Packaging Farmaca (MPF) B.V.","duties_or_roles":"sponsorDuties code: 15 (Labelling and packaging); contact email: info@sharpservices.com","organisation_type":"Pharmaceutical company"}
• {"country":"Austria","full_name":"Az Pollen Research GmbH","duties_or_roles":"sponsorDuties code: 15 (Pollen count data); contact email: office@pollenresearch.com","organisation_type":"Pharmaceutical company"}
• {"country":"Austria","full_name":"Probando GmbH","duties_or_roles":"sponsorDuties code: 15 (Subject Recruitment / Advertisement); contact email: office@probando.io","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Sharp Clinical Services (UK) Limited","duties_or_roles":"sponsorDuties code: 15 (Labelling and packaging); contact email: info@sharpservices.com","organisation_type":"Pharmaceutical company"}