Long-term clinical trial of PQ Grass in paediatric subjects with seasonal allergic rhinitis and/or rhinoconjunctivitis induced by grass pollen

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Allergy Therapeutics (UK) Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Sep 2024 → ongoing

Decision date (initial)

2024-06-17

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: Efficacy, Safety

-Part A: To evaluate the efficacy of PQ Grass 27600 SU in paediatric subjects with grass pollen induced SAR.
-Part B: To evaluate the sustained long-term efficacy of PQ Grass 27600 SU in paediatric subjects.

Secondary objectives 5

1. Part A Efficacy: -To evaluate the efficacy of PQ Grass on the CSMS over the entire GPS. -To evaluate the efficacy of PQ Grass on the dSS and dMS components of the CSMS over the peak GPS. -To evaluate the efficacy of PQ Grass on the TCS over the peak GPS. -To evaluate well days and severe days during the peak GPS. -To evaluate grass specific IgG4. -To evaluate the quality of life.
2. Part A Safety: -To evaluate the safety and tolerability of PQ Grass in paediatric subjects with grass pollen induced SAR.
3. Part B Efficacy: Key secondary: -To evaluate the long-term efficacy of PQ Grass. -To evaluate IgG4 after 3 years of treatment.
4. 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.
5. Part B Safety: -To evaluate the long-term safety and tolerability of PQ Grass in paediatric subjects with grass pollen induced SAR.

Conditions and MedDRA coding

Seasonal allergic rhinitis/rhinoconjunctivitis induced by grass pollen exposure

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000813-PIP01-09

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Written informed consent from a legal representative on the subject’s behalf (with/without assent depending on applicable country-specific regulations).
2. 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.
3. 3. Male or female.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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)
9. 9. Children who are able to perform spirometry or peak flow measurements.
10. 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.
11. 11. Be able to adhere to dose and visit schedule

Exclusion criteria 29

1. 1. Pregnant or lactating subject.
2. 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.
3. 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.
4. 4. Presence of any medical condition that may reduce the ability to survive a serious allergic reaction.
5. 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.
6. 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].
7. 7. Hospital admission for exacerbation of asthma in the 12 months prior to Visit 1 or any history of a life-threatening asthma attack.
8. 8. Presence of non-atopic rhinitis and/or rhino-sinusitis (with or without polyps).
9. 9. Presence of nasal polyps and/or chronic sinusitis.
10. 10. Presence of any acute or chronic ocular disorder, other than allergic conjunctivitis.
11. 11. Presence of any skin conditions (e.g., skin abnormalities, tattoos etc.), which might interfere with the interpretation of the SPT results.
12. 12. Severe eczema with involvement of more than 25% of the body surface.
13. 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.
14. 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.
15. 15. Clinical history of severe or life-threatening anaphylactic reactions to foods, insect venom, exercise, drugs or idiopathic anaphylaxis
16. 16. Clinical history of allergy, hypersensitivity or intolerance to the excipients of the trial medication.
17. 17. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.
18. 18. History of any previous allergen immunotherapy, by any route.
19. 19. Unable to meet medication washout requirements listed in the table prohibited medications.
20. 20. Unable to receive epinephrine therapy or at greater risk of developing adverse reactions after epinephrine administration as assessed by the Investigator.
21. 21. Monoamine oxidase inhibitor medication and tricyclic antidepressants.
22. 22. Β-blocker medication for any indication.
23. 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.
24. 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.
25. 25. Participation in a clinical trial research trial with any IMP within 4 weeks from screening.
26. 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.
27. 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.
28. 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.
29. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. -Part A: The CSMS averaged over the peak GPS during Year 1.
2. -Part B: The CSMS averaged over the peak GPS after 2 years of treatment-free follow-up.

Secondary endpoints 11

1. 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.
2. - 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.
3. 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.
4. - 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.
5. Part B Efficacy: Key secondary endpoints: - 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.
6. - 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).
7. Part B Efficacy: Other secondary endpoints: - The CSMS averaged over the peak GPS after 1 and 2 years of treatment and 1 year of treatment-free follow-up. - The CSMS averaged over the entire (or truncated) GPS after 1 and 2 years of treatment and 1 and 2 years of treatment-free follow-up. - The TCS averaged over the peak GPS after 1 and 2 years of treatment and 1 year of treatment-free follow-up.
8. - 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.
9. - 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.
10. 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.
11. - 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.

Investigational products

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

Test 1

Placebo 1

Auxiliary 12

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 13

Locations

7 EU/EEA countries · 75 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 2 · Art. 52 CTR

Results and documents

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

Documents 295 files

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

Application history

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