A Multi-national Phase IIIb Trial to Determine the Safety and Efficacy of STALORAL® Birch 300 IR in Children and Adolescents 5 to 17 Years old with Allergic Rhinoconjunctivitis induced by Birch Pollen with or without Asthma. STALORAL® Birch 300 IR will be compared to placebo and neither the patients not the doctors will know the treatment taken by the patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stallergenes

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

20 Sep 2023 → 6 Aug 2025

Decision date (initial)

2024-05-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

STALLERGENES, France

External identifiers

EU CT number

2023-509833-38-00

EudraCT number

2022-002012-23

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate clinical efficacy of STALORAL® Birch 300 IR on ARC symptoms and rescue medication use during BPS2 of the trial, in children and adolescents with birch pollen-induced Rhinoconjunctivitis ARC.

Secondary objectives 9

1. To assess the effect of STALORAL® Birch 300 IR on symptoms and medications along with rhinoconjunctivitis-associated QOL score during BPS2 of the trial, in children and adolescents with ARC.
2. To assess combined ARC symptoms and medications score during the worst birch pollen period, each year.
3. To assess combined ARC symptoms and medications scores over 2 consecutive birch pollen seasons.
4. To assess individual symptoms and medication scores over 2 consecutive birch pollen seasons.
5. To assess changes in the ARIA classification.
6. To assess asthma status and control over 2 consecutive birch pollen seasons.
7. To assess OAS over 2 consecutive birch pollen seasons.
8. To assess QOL of patients over 2 consecutive birch pollen seasons.
9. To assess the patient's immunological status over 2 consecutive birch pollen seasons. Due to characters limitations, please see other secondary objectives in Protocol redline version for changes

Conditions and MedDRA coding

Birch Pollen-induced Allergic Rhinoconjunctivitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Able to sign and date the informed consent/assent form prior to any trial-specific procedure. Patients may check a box on the assent form if they are unable to provide a signature. (Parents and/or authorised legal representative(s) will have to give written informed consent for minors in their custody.)
2. Covered by a health insurance system as per local regulation.
3. Demographics and Medical History - Aged ≥5 to ≤17 years old at the randomisation visit.
4. Documented, physician diagnosed, clinically relevant history of moderate to severe ARC induced by birch pollen (with or without asthma) despite having received treatment with symptom-relieving medication during at least 1 previous birch pollen season for ages 4 through 6 or at least 2 previous birch pollen seasons for ages 7 through 17 years at screening.
5. A Retrospective ARC Total Symptom Score (TSS), based on the previous birch pollen season of at least 12 out of a maximum possible score of 18 AND a retrospective score of at least 30 on a general VAS 0-100 on the severity of symptoms as evaluated by the patient or by the parent/authorised legal representative if the patient is not able to perform the assessment, at screening. Retrospective ARC TSS (TSS0-18) is rated the same way as Daily Symptom Score (DSS) (DSS0-18).
6. Screening Tests and Evaluations - Positive Skin Prick Test (SPT) to Betula pendula at screening visit. The SPT is considered positive if it results in a wheal diameter ≥ 3.0 mm [with positive control (histamine) ≥ 3.0 mm and negative control = 0 mm]). The Sponsor will accept to include patients who have a documented positive SPT in their medical records if this SPT was performed during the previous 6 months preceding the screening visit at the same investigational site in which they are enrolled.
7. Positive specific Immunoglobulin E (IgE) to pollen allergens of Betula pendula and Bet v 1 at screening (CAP-RAST birch pollen allergens and Bet v 1 specific IgEs ≥ 0.7 kU/L).
8. Negative urine pregnancy test on all female patients of childbearing potential or who have had their first menarche prior to randomisation.
9. Lifestyle Considerations - Internet access at home or via a portable device so that patients or the parent/authorised legal representative can complete the e-Diary in a dedicated application on a mobile phone daily via internet. Patients will start scoring at randomisation, i.e., 4 months before the pollen season.

Exclusion criteria 20

1. Medical History - Any clinical deterioration of asthma (i.e., asthma exacerbation) that resulted in emergency procedure/treatment or treatment with systemic corticosteroids within 3 months prior to randomisation.
2. For patients ≥7 years old: Reduced lung function at randomisation defined as Forced Expiratory Volume in 1 second (FEV1) < 70% of the predicted value. For patients with asthma, this is assessed on the patient's usual asthma controller medication*. The following wash-out periods apply for asneeded asthma reliever medication at least a 6-hour wash-out of Short- Acting Beta Agonists (SABAs), a 12 hour wash-out of Long-Acting Beta Agonists (LABAs) 24h wash-out for ultra-LABAs and 5 days or 5 halflives for inhaled corticosteroids. *In order to ensure that the asthmatic patients with a mild to moderate asthma status are controlled by treatment steps 1, 2 or 3 in accordance with the Global Initiative for Asthma (GINA 2022), the proper continuous asthma treatment i.e., "controller" is maintained. Only the asthma "reliever" medications must be stopped before performing spirometry. If an asthma medication is used as both "controller" and "reliever", such as inhaled corticosteroids (in combination with formoterol [LABA]), it must not be stopped before performing spirometry.
3. Severe or uncontrolled asthma or asthma treated with asthmatic therapies consistent with steps 4 or 5 as defined by Global Initiative for Asthma (GINA) 2022 received within 12 months prior to entry in the trial. Eligible asthmatic patients will be those with mild and moderate asthma controlled by treatment(s) consistent GINA 2022 treatment with Steps 1, 2 or 3.
4. Severe oral inflammations such as oral lichen planus, oral ulcerations or oral mycosis.
5. Acute or chronic inflammatory or infectious upper airway diseases (excepted mild to moderate asthma) including recurrent acute or chronic sinusitis.
6. History of eosinophilic oesophagitis or with current severe or persistent gastroesophageal symptoms including dysphagia or chest pain that, in the opinion of the investigator, may constitute an increased safety concern.
7. A relevant history of systemic allergic reaction (e.g., anaphylaxis with cardiorespiratory symptoms, generalised urticaria or severe facial angioedema) that, in the opinion of the Investigator, may constitute an increased safety concern.
8. Any disease that prohibits the use of adrenaline (e.g., hyperthyroidism).
9. Any severe, uncontrolled disease that, upon Investigator judgment, could increase the risk for trial patients (including but not limited to cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, haematological disorders, diseases of the immune system including autoimmune diseases [upon the Investigator's judgment based on the benefit/risk assessment] and immune deficiencies of current clinical relevance, active malignancies).
10. Screening Tests and Evaluations. A documented clinically relevant history of seasonal ARC symptoms caused by an allergen source, other than tree pollen from the birch homologous group, with a season overlapping the BPS.
11. A documented clinically relevant history of perennial ARC symptoms caused by an allergen source such as animal dander to which the patient is exposed during the BPS.
12. Any significant abnormal laboratory parameter or alteration in vital signs that could increase the risk for the patient, in the opinion of the Investigator.
13. Medication - Ongoing treatment with prohibited treatment as listed in Section 8.2.3 or any allergen immunotherapy product including Specific Immunotherapy (SIT) or past full courses of SIT against birch pollen terminated for less than 5 years or past courses of SIT for other allergens terminated for less than 6 months prior to start of randomisation.
14. Patients requiring continuous treatment with systemic corticosteroids for any indications.
15. Patients requiring continuous treatment with β-blockers or with Monoamine Oxidase Inhibitors (MAOIs).
16. Treatment with an immunosuppressive (ATC code L04 or L01) within 3 months prior to the screening visit.
17. Hypersensitivity to any excipient of the IMP/placebo, or contraindication to the use of RMs (i.e., antihistamine and nasal corticosteroids).
18. Patients following a strict low sodium diet as the IMP treatment contains 590 mg of sodium chloride per vial in a 10 mL solution.
19. Inability to adhere to the washout periods as defined by the protocol, with respect to screening and to refrain from using the medications indicated until after the trial is complete.
20. Patients who would be likely to require prohibited concomitant therapy during the trial or who are anticipated to require using of such agents during the trial. Any medication given for an AE will be permitted.For other exclusion criteria, please refer to the section 7.2 of the Protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint will be the average ARC TCS (TCS0-38) over the entire BPS2.

Secondary endpoints 5

1. The average CSMS (CSMS0-6) over the entire BPS2.
2. The average ARC DSS (DSS0-18) over the entire BPS2.
3. The average ARC DMS (DMS0-20) over the entire BPS2
4. The rhinoconjunctivitis-associated functional problems as measured with the RQLQ(S) average overall score for adolescents aged between 12 to 17 years over the entire BPS2.
5. The rhinoconjunctivitis-associated functional problems as measured with the PRQLQ average overall score for children between 6 to 11 years over the entire BPS2. Please refer to Section 10 of the Protocol for a full description of the assessments of efficacy.

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stallergenes

Sponsor organisation

Stallergenes

Address

6 Rue Alexis De Tocqueville

City

Antony

Postcode

92160

Country

France

Scientific contact point

Organisation

Stallergenes

Contact name

Jaime SÁNCHEZ LÓPEZ

Public contact point

Organisation

Stallergenes

Contact name

Jaime SÁNCHEZ LÓPEZ

Third parties 3

Locations

12 EU/EEA countries · 83 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

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 10 files

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

Application history

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