Randomised efficacy and safety clinical trial of PQ Birch in subjects with seasonal allergic rhinitis and/or rhinoconjunctivitis induced by birch pollen.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Allergy Therapeutics (UK) Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2024-10-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Allergy Therapeutics (UK) Ltd.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of PQ Birch 27300 SU in subjects with birch pollen-induced SAR and/or rhinoconjunctivitis

Secondary objectives 1

1. Secondary Efficacy: - To evaluate the efficacy of PQ Birch on the CSMS over the entire BPS. - To evaluate the efficacy of PQ Birch on the dSS and dMS components of the CSMS over the peak BPS. - To evaluate the efficacy of PQ Birch on the TCS over the peak BPS. - To evaluate the efficacy of PQ Birch on the CSMS over the peak TPS. - To evaluate the disease specific burden on quality of life. - To evaluate the effect of PQ Birch on IgG4. Safety: To evaluate the safety and tolerability of PQ Birch in subjects with birch pollen-induced SAR and/or rhinoconjunctivitis.

Conditions and MedDRA coding

seasonal allergic rhinitis and/or rhinoconjunctivitis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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.
2. 2. Subject who has a signed and dated ICF.
3. 3. Subject must be 18 to 65 years of age inclusive, at the time of signing the ICF.
4. 4. Male or female.
5. 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.
6. 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.
7. 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.
8. 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.
9. 9. A positive SPT for birch pollen (wheals [longest diameter] ≥3 mm).
10. 10. Birch-specific IgE class ≥2 (i.e., ≥0.71 kUA/L) as documented by an ImmunoCAP test at screening.
11. 11. Forced expiratory volume in one second (FEV1) ≥70% of predicted and PEFR ≥70% of predicted at screening.

Exclusion criteria 40

1. 1. Pregnant or lactating subject.
2. 2. Presence of any medical history of moderate to severe allergy symptoms.
3. 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.
4. 4. Presence of any medical condition that may reduce the ability to survive a serious allergic reaction.
5. 5. Presence of active systemic autoimmune disorder, systemic autoimmune disorders in remission or active organ specific autoimmune disorder.
6. 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.
7. 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.
8. 8. Presence of severe or poorly controlled or uncontrolled asthma as defined in the protocol.
9. 9. Presence of non-atopic rhinitis.
10. 10. Presence 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.
11. 11. Presence of nasal polyps.
12. 12. Eye surgery within the past 6 months.
13. 13. Presence of any skin conditions (e.g., skin abnormalities, tattoos etc.), which might interfere with the interpretation of the SPT results.
14. 14. Clinical history of Type I diabetes or poorly controlled Type II diabetes.
15. 15. Moderate to severe upper or lower respiratory infections requiring medication within 14 days before Visit 1.
16. 16. Presence of acute or chronic infection, fever or inflammation at Visit 1 or Visit 1a.
17. 17. Clinical history of serious systemic reaction in response to AIT in the past.
18. 18. Clinical history of life-threatening anaphylactic reactions to foods, insect venom, exercise, drugs or idiopathic anaphylaxis.
19. 19. Clinical history of allergy, hypersensitivity or intolerance to the excipients of the investigational drug/placebo.
20. 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.
21. 21. Clinical history of hereditary angioedema.
22. 22. Clinical history of mast cell disorder including mastocytosis, chronic urticaria or urticaria pigmentosa.
23. 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).
24. 24. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.
25. 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.
26. 26. Any history of AIT of any type for birch or tree pollen allergy in the past (irrespective of how long ago this was).
27. 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.
28. 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.
29. 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).
30. 30. Previous history of epinephrine auto-injector use.
31. 31. β-blocker medication (local or systemic, including eye drops) for any indication.
32. 32. Monoamine oxidase inhibitors and tricyclic antidepressants.
33. 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).
34. 34. Current or past therapy (within the previous 5 years) with any other immunomodulatory therapies.
35. 35. Unable to refrain from any vaccination (including influenza vaccine) during the clinical trial (unless administered >30 days prior to randomisation).
36. 36. Participation in a clinical research trial with any investigational drug within 4 weeks of Visit 1 or concomitantly with this clinical trial.
37. 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.
38. 38. Vulnerable subjects or those in judicial or governmental detention, detainment or imprisonment in a public institution.
39. 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.
40. 40. Have changed residence to an area with dissimilar pollen burden (s) since the last BPS.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CSMS averaged over the peak BPS.

Secondary endpoints 3

1. 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.
2. - Serum birch-specific IgG4 at pre-BPS (Visit 9) compared to baseline.
3. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Allergy Therapeutics (UK) Limited

Sponsor organisation

Allergy Therapeutics (UK) Limited

Address

Dominion Way

City

Worthing

Postcode

BN14 8SA

Country

United Kingdom

Scientific contact point

Organisation

Allergy Therapeutics (UK) Limited

Contact name

Clinical Research Management

Public contact point

Organisation

Allergy Therapeutics (UK) Limited

Contact name

Clinical Research Management

Third parties 8

Locations

3 EU/EEA countries · 58 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 65 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications