E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Birch pollen-related allergic rhinitis / rhino-conjunctivitis |
|
E.1.1.1 | Medical condition in easily understood language |
Birch pollen-related allergic rhinitis / rhino-conjunctivitis |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001723 |
E.1.2 | Term | Allergic rhinitis |
E.1.2 | System Organ Class | 100000004855 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001726 |
E.1.2 | Term | Allergic rhinitis due to pollen |
E.1.2 | System Organ Class | 100000004870 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001728 |
E.1.2 | Term | Allergic rhinoconjunctivitis |
E.1.2 | System Organ Class | 100000004853 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066093 |
E.1.2 | Term | Birch pollen allergy |
E.1.2 | System Organ Class | 100000004870 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this trial is to establish the optimal dose of SULGEN® Spray Birke in terms of benefit-risk balance. To assess the efficacy of four different doses of SULGEN® Spray Birke compared between each other and to placebo. The primary efficacy endpoint is defined as percentage of patients with an increased dosing step 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 five study groups. This is based on the change of the response to tNPT with incremental concentrations of an allergen extract of Betula verrucosa from baseline to end of treatment.
|
|
E.2.2 | Secondary objectives of the trial |
To assess the efficacy of four different doses of SULGEN® Spray Birke compared between each other and to placebo by the change in the number of dosing steps (pre-post difference) needed to provoke a positive response in the tNPT from baseline to end of treatment in each of the five study groups. To analyse the safety and tolerability of four different doses of SULGEN® Spray Birke compared between each other and to placebo by number of treatment-emergent adverse drug reactions and number of patients affected in each group.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 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 or without well controlled mild-to-moderate asthma defined in GINA guideline (Global Initiative for Asthma, 2017). • Forced expiratory volume (FEV1) in one second > 70 % of predicted normal value (only for asthmatic patients) • Sensitization to birch 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 birch ≥ 0.7 kU/L (CAP EAST class ≥ 2) and positive response to nasal provocation with birch pollen allergen extract (at least at the fourth concentration step) • Assumed compliance and ability of the patient to understand the patient´s diary and to follow the instructions of the study staff
|
|
E.4 | Principal exclusion criteria |
• Previous immunotherapy with tree 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 to any perennial or seasonal allergen with clinical manifestations or co-allergies, whose allergic symptoms interfere with the conduct of the study (e. g. with the tNPT) • Simultaneous participation in other clinical trials • Simultaneous specific immunotherapy with other allergens • Participation in a clinical trial in the last three months before enrolment • Asthmatic patients with forced expiratory volume (FEV1) ≤ 70 % of predicted normal value • Partly controlled or uncontrolled asthma according to GINA guideline (Global Initiative for Asthma, 2017) • Severe acute or chronic inflammatory or infectious diseases • Diseases of the immune system such as autoimmune and immune deficiencies (with exception to well controlled Hashimoto thyroiditis and type-1 diabetes mellitus) • Chronic or acute diseases of the heart, kidney or liver with severe impairment of their function • Hypersensitivity to excipients of the IMP • Any severe or unstable lung disease e. g. active tuberculosis, cystic fibrosis, COPD • 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 • Malignancy within the previous 5 years • Alcohol, drug, or medication abuse within the past year and/or during the study • Use of non-allowed medication (see section 5.3.1) • Contraindications for SPT • Contraindications for NPT • Relationship or dependence with the sponsor and/or investigator • Legal incapacity • Patients who are jurisdictional or governmentally institutionalized • Serious systemic reactions to allergen-specific immunotherapy in the past • Active chronic urticaria • Active severe atopic eczema • Existing or intended pregnancy, lactation or inadequate contraceptive measures for woman with child-bearing potential or a positive pregnancy test at screening • Severe psychiatric, psychological, or neurological disorders; completed or ongoing long-term treatment with tranquilizers or psychactive drugs (including tricyclic antidepressants) • Risk of non-compliance by the patient with study procedures
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
To assess the efficacy of four different doses of SULGEN® Spray Birke compared between each other and to placebo. The primary efficacy endpoint is defined as percentage of patients with an increased dosing step 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 five study groups. This is based on the change of the response to tNPT with incremental concentrations of an allergen extract of Betula verrucosa from baseline to end of treatment.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
9 months after start of trial |
|
E.5.2 | Secondary end point(s) |
To assess the efficacy of four different doses of SULGEN® Spray Birke compared between each other and to placebo by the change in the number of dosing steps (pre-post difference) needed to provoke a positive response in the tNPT from baseline to end of treatment in each of the five study groups. To analyse the safety and tolerability of four different doses of SULGEN® Spray Birke compared between each other and to placebo by number of treatment-emergent adverse drug reactions and number of patients affected in each group. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
9 months after start of trial |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |