E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients, 18-65 years of age, suffering from moderate to severe allergic Rhinitis/Rhinoconjunctivitis to birch pollen during the two preceding birch pollen seasons.
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E.1.1.1 | Medical condition in easily understood language |
birch pollen induced allergy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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 |
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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 |
To demonstrate the efficacy of a two months pre-seasonal treatment with AllerT 50 μg maintenance dose compared to placebo in reducing symptoms of and medication use in allergic Rhinitis/Rhinoconjunctivitis during the following birch pollen season |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the efficacy of a two months pre-seasonal treatment with AllerT 10 μg maintenance dose in reducing symptoms of and medication use in allergic Rhinitis/Rhinoconjunctivitis during the following birch pollen season
To evaluate the safety and tolerability of a two months pre-seasonal treatment with AllerT at maintenance doses of 50 μg and of 10 μg
To evaluate the effects of a two months pre-seasonal treatment with AllerT at maintenance doses of 50 μg and 10 μg during the following birch pollen season on:
o Subjects' quality of life
o Other clinical endpoints including night-time symptoms, number of well days, number of days with severe symptoms and subject’s global evaluation of treatment efficacy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men or women aged 18 to 65 years
2. Subjects presenting moderate to severe allergic Rhinitis/Rhinoconjunctivitis to birch pollen confirmed at screening by all of the following criteria:
a. Score of symptoms of the Rhinoconjunctivitis Symptom Score (RSS) ≥ 12 during the two consecutive preceding birch pollen seasons based on subject’s interview by the investigator
b. Previous use of anti-allergy medications during the two preceding birch pollen seasons based on subject’s interview by the investigator
c. Positive SPT to birch pollen extract (wheal ≥ 5 mm larger than the diluent control)
d. Positive specific IgE CAP test for Bet v 1 (≥ 3 kU/L)
3. Women of childbearing potential under continuous effective contraception during the treatment period
a. This includes: established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; true abstinence (periodic abstinence and withdrawal are not acceptable) or vasectomised male partner, provided that he is the sole partner of that subject.
4. Subjects having been informed and having provided signed consent for participating in the trial and willing to follow all planned trial assessments
Included subjects must not be entered more than once into the trial. |
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E.4 | Principal exclusion criteria |
1. Received specific immunotherapy against:
a. Any allergen within five (5) years before the screening visit
b. Birch pollen or a tree pollen mix including birch pollen at any time before the screening visit
2. Clinical symptoms due to allergens other than birch pollen during the expected birch pollen season (e.g. perennial allergies, allergies to other pollens with a season overlapping the birch pollen season). Patients sensitized to alder and/or hazel may be included provided that the clinical symptoms is caused by their birch allergy.
3. Persistent non-controlled asthma; subjects with a Forced Expiratory Volume (FEV1) lower than 85% of predicted value (see FEV1 predicted and 85% of predicted values in Appendix 12.3) and/or subjects under chronic treatment for asthma. Subjects with seasonal asthma may be included if they are controlled with beta-2-agonist and low dose inhaled corticosteroid (below or equal to budesonide 400 micro-gram on a daily basis).
4. History of severe anaphylactic reaction (grade 4 reaction as per the definitions given in Appendix 12.1)
5. History of any debilitating disease and/or severe medical condition able to influence the course of the trial or the ability of the subjects to fulfill the requirements of the trial
6. Any confirmed or suspected primary or secondary immunodeficiency condition, including human immunodeficiency virus (HIV) infection and asplenia
7. Pregnant or lactating women or women willing or intending to become pregnant during the trial
8. Suspected or known current alcohol or any drug abuse
9. Any other significant finding which, in the opinion of the investigator, would increase the risk of having an adverse outcome from participating in this protocol or of dropping out of the trial
10. Subjects intending to travel during the birch pollen season outside of the birch pollination area for more than seven consecutive days
11. Subjects unable or unwilling to record allergy symptoms and medications daily during the following birch pollen season using an electronic diary device
12. Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
13. Beta-blockers or ACE-inhibitors within four weeks prior to randomization, or planned to be used during the treatment period
14. Immunosuppressive medication (including steroids) within four weeks prior to randomization, or planned to be used during the trial period
15. Use of anti-depressant medication with antihistamine effect within two weeks prior to randomization
16. Use of any investigational or non-registered drug, vaccine or medical device within four weeks prior to randomization, or planned to be used during the trial period |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the average of the combined Rhinoconjunctivitis Symptom and Medication Score (CSMS) obtained daily during the birch pollen season. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Start day of birch pollen season until end day of birch pollen season. |
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E.5.2 | Secondary end point(s) |
Average of the total score of the quality of life questionnaires obtained weekly during the birch pollen season using the validated Mini-RQLQ questionnaire
Average of the Night-time Nasal Symptom Score (NNSS) obtained daily during the birch pollen season
Average of the combined Rhinoconjunctivitis and Night-time Symptom and Medication Score (CNSMS) obtained daily during the birch pollen season
Percent of Well Days during the birch pollen season
Percent of Days with Severe Symptoms during the birch pollen season
Subject’s global evaluation of treatment efficacy collected at the end of the birch pollen season both on a categorical scale as well as on a VAS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Start day of birch pollen season until end day of birch pollen season. |
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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 | No |
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 | 3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | No |
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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |