Phase II-III study to assess the efficacy and safety of sublingual immunotherapy in patients suffering from birch pollen allergy

Start 22 Aug 2023 · End 12 Oct 2024 · Status Ended · 1 EU/EEA countries · 2 sites

Overview

Sponsor-declared trial summary

Phase Phase II and Phase III (Integrated)

Status Ended

Participants planned 512

Countries 1

Sites 2

Moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to birch pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline

The purpose of this trial is to establish the most effective and best tolerated dose of SULGEN® Spray Betula verrucosa in terms of benefit-risk balance and CSMS (Combined Symptom and Medication Score).

Key facts

Sponsor: ROXALL Medizin GmbH
Participant type: Patients
Age range: 18-64 years
Gender: Male and Female
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Trial duration: 22 Aug 2023 → 12 Oct 2024
Decision date (initial): 2023-08-22
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: Roxall Medizin GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Dose response

The purpose of this trial is to establish the most effective and best tolerated dose of SULGEN®
Spray Betula verrucosa in terms of benefit-risk balance and CSMS (Combined Symptom and
Medication Score).

Conditions and MedDRA coding

Moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to birch pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline

Regulatory references

EMA paediatric investigation plan (PIP): EMEA-000959-PIP01-10

EU CT number	Title	Sponsor
2011-002319-27	Phase II study to assess the tolerability, safety and efficacy of sublingual immunotherapy in patients suffering from birch pollen allergy
2023-505567-37-01	Phase II-III study to assess the efficacy and safety of sublingual immunotherapy in patients suffering from birch pollen allergy	ROXALL Medizin GmbH

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

Patients who signed and dated the informed consent form obtained prior to any study specific examination
Female or male patients between 18 and 65 years of age at the time of signing the informed consent form
Patients with moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to birch pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline
Patients with well-controlled mild-to-moderate or without asthma defined in GINA guideline (Global Initiative for Asthma, 2022).
Forced expiratory volume (FEV1) in one second > 70 % of predicted normal value (only for asthmatic patients)
Sensitization to Betula verrucosa pollen, verified by: − positive skin prick test (wheal diameter ≥ 3 mm and negative control < 2 mm and positive (histamine) control ≥ 3 mm) and − serum allergen-specific IgE to Betula verrucosa ≥ 0.7 kU/L (CAP EAST class ≥ 2) and − a Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) ≥ 2 (0-3 scale) based on the most severe days during one of the two BPS preceding enrolment and − positive response to nasal provocation with Betula verrucosa pollen allergen extract (at least at the third concentration step)
Assumed compliance and ability of the patient to understand the patient’s electronic diary and to follow the instructions of the study staff
Compliance and ability of the patient to complete an electronic diary for self-evaluation of the symptoms and rescue medication
Safety laboratory results within the normal range or considered to be not clinically significant in any other case

Exclusion criteria 32

Previous immunotherapy with birch pollen allergen extracts according to the homologous group of tree pollen of the "Birch group" / "Fagales group", as defined in Annex 1 in the Guideline on allergen products: production and quality issues (EMEA/CHMP/BWP/304831), within the last 5 years
Patients with co-sensitizations or co-allergies to any perennial or seasonal allergen (with exception of alder, hazel and hornbeam), which interfere with the conduct of the study (e. g. with the tNPT), especially if the result in SPT for this allergen is higher than that for Betula verrucosa
Patients with co-sensitizations to any mould or pollen with overlapping season but which are not cross-reactive with Betula verrucosa and with specific IgE levels ≥ class 2 CAP/PHADIA (unless the relevance can be excluded by component resolved diagnosis)
Simultaneous participation in other clinical trials
Simultaneous specific immunotherapy with other allergens
Participation in a clinical trial in the last three months before enrolment
Contraindications for SLIT (Pitsios et al., 2015)
Contraindications for SPT
Contraindications for NPT
Serious systemic reactions to allergen-specific immunotherapy in the past
Hypersensitivity to excipients of the IMP
Any severe or unstable lung disease e. g. active tuberculosis, cystic fibrosis, COPD
Severe, or partly controlled or uncontrolled asthma according to GINA guideline (Global Initiative for Asthma, 2022)
Asthmatic patients with FEV1 ≤ 70 % of predicted normal value at screening
Chronic or severe acute diseases of nose or eyes
Irreversible secondary disorders of the target organs (e. g. emphysema, bronchiectasis)
Therapy with immunoglobulins
Completed or ongoing treatment with anti-IgE-antibody
Diseases of the immune system including autoimmune and immune deficiencies (with exception to well-controlled Hashimoto thyroiditis and type-1 diabetes mellitus)
Severe acute or chronic inflammatory or infectious diseases
Chronic or acute diseases of the heart, kidney or liver with severe impairment of their function
Malignancy within the previous 5 years
Active chronic urticaria
Active severe atopic eczema
Alcohol, drug, or medication abuse within the past year and/or during the study
Existing or intended pregnancy, lactation or inadequate contraceptive measures for woman with childbearing potential or a positive pregnancy test at screening
Use of non-allowed medication
Severe psychiatric, psychological, or neurological disorders; completed or ongoing longterm treatment with tranquilizer or psychoactive drugs (including tricyclic anti-depressants)
Relationship or dependence with the sponsor and/or investigator
Legal incapacity
Patients who are jurisdictional or governmentally institutionalized
Risk of non-compliance by the patient with the study procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

The primary (efficacy) endpoint is defined as the absolute differences in mean CSMS (Combined Symptom and Medication Score) during Peak Birch Pollen Period (PBPP) of each active treatment group compared to placebo treatment group.

Secondary endpoints 9

Absolute and relative differences in mean CSMS during Birch Pollen Season (BPS) between active and placebo treatment groups.
Absolute and relative differences in mean dSS during PBPP and BPS.
Absolute and relative differences in mean dMS during PBPP and BPS
Global Rhinoconjunctivitis Discomfort with a Visual Analogue Scale (VAS)
Change in Rhinoconjunctivitis quality of life questionnaire (RQLQ) between active and placebo treatment groups comparing basal and post-treatment scoring
Well and severe days: A well day is defined as a day without administration of any rescue medication (dMS = 0) and with dSS < 0.34 (range 0-3). A severe day is defined (acc. to Pfaar et al. 2014a) as a day with a single score = 3 in any of the six symptoms. Percentages of well and severe days will be calculated for each subject as the number of well or severe days in the PBPP and BPS in relation to the number of days comprising both periods.
Symptom-free days are defined as the days with absence of symptoms (dSS = 0) and without administration of any rescue medication (dMS = 0), expressed as percentage of days during the PBPP and BPS.
tNPT titrated Nasal Provocation Test: To assess the efficacy of each dose of SULGEN® Spray Betula verrucosa compared to placebo. Defined as percentage of patients with an increased dosing step and the change in number of dosing steps needed to provoke a positive response in the titrated nasal provocation test (tNPT) post-treatment compared with pre-treatment (i. e. any improvement) in each of the four treatment groups. This is based on the change of the response to nasal provocation (tNPT) with
To analyse the safety and tolerability of each dose of SULGEN® Spray Betula verrucosa compared to placebo by Treatment-Emergent Adverse Drug Reactions (TEADR) and patients affected with TEADRs in each group