E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Birch pollen allergic Rhinoconjunctivitis |
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E.1.1.1 | Medical condition in easily understood language |
rhinoconjunctivitis due to birch pollen allergy
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066093 |
E.1.2 | Term | Birch pollen allergy |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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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 |
The main objective of the trial is to assess the sustained clinical efficacy on the Average Adjusted Symptom Score (AAdSS): a score taking into account the daily Rhinoconjunctivitis Total Symptom Scores (RTSSs) and daily rescue medication usage of a 300 IR dose of a birch pollen allergen extract sublingual solution, administered once daily during 5 months per year, after 2 consecutive years in patients with birch pollen allergy. |
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E.2.2 | Secondary objectives of the trial |
The Average Adjusted Symptom Score AAdSS on non-primary efficacy analysis sets and/or other evaluation periods. The Average Adjusted Symptom Score AAdSS in three subgroups of pooled sites grouped according to the mean AAdSS in the placebo group (AAdSS by tertiles).The Average Rhinoconjunctivitis Total Symptom Score ARTSS of the six rhinoconjunctivitis symptoms sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus and watery eyes The Average Rescue Medication Score ARMS and use of rescue medication Each of the six individual Average Rhinoconjunctivitis Symptom Scores ARSS. The Average Combined Score ACS: A score taking into account the Rhinoconjunctivitis Total Symptom Score RTSS and the Rescue Medication Score RMS The intensity of Rhinoconjunctivitis symptoms using a Visual Analogue Scale RVAS score The standardized Rhinoconjunctivitis Quality of Life Questionnaire score RQLQ(S) The Proportion of Symptom-Controlled Days (PSCDs) To document the safety of the treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The main inclusion criteria are:
- Male or female outpatients aged 18 to 65 years (inclusive).
- Symptomatic birch pollen-related allergic rhinoconjunctivitis for at least the previous 2 pollen seasons requiring intake of symptomatic treatment.
- Sensitization to birch pollen demonstrated by:
•A positive SPT to birch pollen with wheal diameter > 3 mm.
•Birch pollen allergens specific IgE levels ≥ 0.70 kU/L.
- RRTSS based on the previous or on the penultimate birch pollen season ≥ 12 out of a maximum possible score of 18.
- Patients with an FEV1 ≥ 80% of the predicted value.
- Patients who are willing to comply with the protocol.
- Patients having given a signed informed consent before completing any study related procedure.
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E.4 | Principal exclusion criteria |
Exclusion Criteria:
-Patients with symptoms of rhinitis/rhinoconjunctivitis during the birch pollen season due to any other allergens (except alder and hazel). This includes patients with symptomatic allergic rhinitis/rhinoconjunctivitis due to cat or dog allergens, and living with these animals at home or at risk of frequent contacts with these animals (family, friends etc.) during the course of the study.
-Patient who previously received desensitization treatment to birch pollen and/or another Betulaceae sp. (for example hazel or alder) within the previous 5 years.
-Patients with ongoing treatment by immunotherapy with another allergen.
-Pregnancy (positive pregnancy test), breast-feeding.
-Female patients of childbearing potential planning a pregnancy during this study or not using a medically accepted contraceptive method (hormonal birth control [orally, injectable or by implant, for at least 2 months before enrolment], intrauterine device, spermicide used with a male condom, bilateral tubal ligation, diaphragm with spermicide, female condom, monogamous relationship with a vasectomised partner).
- Patients planning to move during the study or planning to leave the area during the birch pollen season for more than 1 week (7 consecutive days).
- Patients with moderate or severe persistent asthma (GINA 3 or 4).
- Patients with seasonal mild persistent asthma (GINA 2) necessitating treatment with inhaled glucocorticosteroids at a dose level greater than 400 mcg budesonide dose-equivalents.
- Patients with any nasal or oral condition that could interfere with the efficacy or safety assessments (such as nasal polyposis or oral inflammation).
- Patients with severe immune deficiency.
- Patients with a past or current disease, which as judged by the Investigator, may affect the patient’s participation in or outcome of this study.
- Any other disease or condition which would place a patient at undue risk by being included in the study (according to the Investigator’s opinion).
- Usual contra-indications of immunotherapy such as concomitant beta-blocker therapy whatever the route and/or immunosuppressive drugs.
- Patients treated with inhaled/systemic steroids (whatever the indication) within 4 weeks prior to Visit 1 (Screening), or with long acting systemic corticosteroids 12 weeks before Visit 1 (Screening).
- Patients under continuous corticotherapy (inhaled or systemic drugs).
- Patients following a strict low sodium diet as the study treatment contains 590 mg of sodium chloride per vial in a 10 mL solution.
- Investigators, co-Investigators, as well as their children or spouses and all study collaborators.
- Patients who have participated in any clinical trial within 3 months prior to this one.
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E.5 End points |
E.5.1 | Primary end point(s) |
The Average Adjusted Symptom Score (AAdSS) while on treatment during the second pollen period is the primary efficacy endpoint for the sustained clinical efficacy. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
end of study, after two years of treatment
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E.5.2 | Secondary end point(s) |
ARTSS during the evaluation periods while the patient is on treatment.
ARMS during the evaluation periods while the patient is on treatment.
ARSS during the evaluation periods while the patient is on treatment.
ACS during the evaluation periods while the patient is on treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
end of study, after two years of treatment
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 | Information not present in EudraCT |
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
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |