| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Allergic rhinitis and/or rhinoconjunctivitis, with or without intermittent asthma, caused
by birch pollen. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001723 |
| E.1.2 | Term | Allergic rhinitis |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039097 |
| E.1.2 | Term | Rhinoconjunctivitis |
|
| 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 objective of the study is to assess the efficacy and safety of 4 doses depigmented and glutaraldehyde polymerized allergenic extract of 100% birch pollen(Depigoid® Birch) in birch pollen-induced patients suffering from allergic rhinitis and/or rhinoconjunctivitis.
The primary criterion is the comparison between patients treated with Depigoid® Birch (100, 1,000, 5,000 or 10,000 DPP/mL) with regard to the percentage of patients who need an increased amount of allergen to provoke a positive CPT at the end of treatment (to compare the slope of efficacy). |
|
| E.2.2 | Secondary objectives of the trial |
Efficacy variables:
• Laboratory parameters (total IgE, specific IgE, specific IgG1 and specific IgG4),
• Conjunctival provocation test (CPT).
Safety variables:
• Laboratory parameters (hematology & clinical chemistry),
• Adverse events,
• Vital signs,
• Physical examination,
• Patient diary,
• Global evaluation. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients will be eligible for inclusion into the study only if all of the following criteria
are met:
1. Patients have provided an appropriately signed and dated informed consent prior to any study specific examination,
2. Patients must be ≥ 18 and ≤ 70 years of age at Visit 1,
3. Patients must have a perception of disease activity of at least 30 mm on a 100 mm
visual analogue scale (VAS),
4. Patients must have an FEV1 or PEF value > 80% of the predicted normal value, (for PEF: highest result of 3 measurements),
5. Patients must complain about allergic rhinitis and/or rhinoconjunctivitis symptoms for at least 2 years with or without intermittent asthma symptoms, caused by clinical
sensitization against birch pollen,
6. IgE-mediated sensitization has to be verified by:
• suggestive medical history, and
• specific IgE against birch pollen (CAP-Rast ≥ 2), and
• a positive skin prick test (SPT) to birch pollen (the SPT is considered positive
if it results in a wheal diameter of at least 3 mm and at least the size of
histamine reference), and
• a positive conjunctival provocation test (CPT) with a birch pollen concentration
of 10,000 SQ-units/mL. Ten minutes after applying the drop, 4 symptom
categories (eye redness, weeping, itching or burning, nose dripping or blockage)
will be assessed and scored from 0 to 3 (0 = absent, 1 = mild,
2 = moderate, 3 = severe). The CPT is evaluated as positive if a sum score
of 5 is reached (21). The following concentrations will be applied: 100, 330,
1,000, 3,300 and 10,000 SQ-units/mL.
Special criteria for patients with co-allergies
For all patients with co-allergies as a result of sensitization against grass and/or weed pollen and/or perennial allergens (e.g. house dust mites, animal dander), all of the following inclusion criteria must be fulfilled:
7. Patients do not suffer from typical symptoms against co-allergens,
8. Specific CAP-RAST against co-allergens (perennial allergens) < CAP-RAST against
birch pollen (the difference has to be ≥ 2), patients with co-allergens against animal dander can be randomized even if the CAP RAST is ≤ 2, but must not be exposed to the specific allergen.
9. Result of SPT against co-allergens < result of SPT against birch pollen.
|
|
| E.4 | Principal exclusion criteria |
A patient will not be eligible for inclusion in this study if any of the following criteria
are met:
1. Acute and chronic conjunctivitis,
2. Infectious conjunctivitis,
3. History of significant clinical manifestations of allergy as a result of sensitization
against grass or weed pollen and perennial allergens (e.g. house dust mites),
4. Symptoms due to co-allergies,
5. Persistent asthma, according to the Global Initiative for Asthma (GINA) Guidelines (see Section 7.9.1),
6. Acute or chronic inflammatory or infectious airway diseases including recurrent
acute or chronic sinusitis,
7. Chronic structural diseases of the lung (e.g. emphysema or bronchiectasis),
8. Diseases of the immune system including autoimmune and immune deficiencies,
9. Any disease, which prohibits the use of adrenaline (e.g. hyperthyroidism),
10. Severe uncontrolled diseases that could increase the risk for the patients
participating in the study, which include but are not limited to the following:
cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or hematological
disorders,
11. Any malignant disease during the previous 5 years,
12. Any significant abnormal laboratory parameter or alteration in the vital signs that
could increase the risk for the study patient,
13. Alcohol, drug, or medication abuse within the past year,
14. Severe psychiatric, psychological, or neurological disorders,
15. Use of immunotherapy against birch pollen within the
last 5 years,
16. Topical and systemic treatment with β-blockers,
17. Treatment with substances interfering with the immune system within 1 week prior to Visit 2,
18. Use of tranquillizers or psychoactive drugs within 1 week prior to Visit 1,
19. Use of systemic corticosteroids within 3 months prior to Visit 1,
20. Immunization with vaccines within 7 days prior to Visit 2,
21. Patients with hypersensitivity to excipients of the investigational medicinal
product,
22. Patients expected to be non-compliant and/or not co-operative,
23. Participation in any other clinical study within 30 days prior to Visit 2,
24. Patients who have already participated in this study,
25. Patients who are employees of the institution, or 1st grade relatives, or partners of the investigator,
26. Any donation of germ cells, blood, organs, or bone marrow during the course of
the study,
27. Patients who are not contractually capable,
28. Nursing (lactating) women or a positive pregnancy test at Visit 1. In general,
women of childbearing potential should be using highly effective contraception to
participate in clinical studies. A highly effective method of birth control is defined
as one which results in a low failure rate (i.e., less than 1% per year) when used
consistently and correctly, such as implants, injectables, combined oral
contraceptives, some IUDs, sexual abstinence or vasectomised partner.
29. Persons who are jurisdictionally or governmentally institutionalized. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is the comparison between the 4 treatment groups with regard to the percentage of patients who need an increased amount of birch allergen to provoke a positive CPT at the end of the treatment (to compare the slope of efficacy). The CPT against birch pollen will be performed at Visit 1 with a birch pollen concentration of 100, 330, 1,000, 3,300 and 10,000, and at the study end visit (V8) with doses of 100, 330, 1,000, 3,300, 10,000, 33,000, and 100,000 SQ-U/mL. An aqueous diluent will serve as negative control. |
|
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| four doses of Depigoid® Birch |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 47 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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
|
| According to the protocol |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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