| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| seasonal allergic rhinoconjunctivitis due to birch pollen |
|
| E.1.1.1 | Medical condition in easily understood language |
| hay fever due to birch pollen |
|
| 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 | 17.1 |
| 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.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to assess the difference in change (baseline to post-treatment) in total symptom score (TSS) recorded following application of a CPT between four POLLINEX Quattro® Birch treatment arms of 600SU, 1550SU, 5100SU and 13600 (cumulative doses), respectively. |
|
| E.2.2 | Secondary objectives of the trial |
Efficacy:
1. To compare proportions of subjects with negative CPT after treatment between four POLLINEX Quattro® Birch treatment arms
2. To compare change (baseline to post-treatment) in allergen concentration required for eliciting of a positive CPT
3. To compare change (baseline to post-treatment) in individual symptom scores (ISS) between four POLLINEX Quattro® Birch treatment arms
4. To compare immunological (Birch specific IgG, IgG4 and IgE) differences (baseline to post-treatment) between four POLLINEX Quattro® Birch treatment arms
Safety/Tolerability:
1. To compare the tolerability of different subcutaneous doses.
2. To compare the tolerability of cumulative subcutaneous doses .
3. To compare the frequency of adverse events (AEs).
4. To compare the frequency of adverse reaction complexes (ARCs)
5. To compare the proportion of subjects not completing the treatment regimen due to AEs.
6. To compare changes in routine clinical laboratory values and vital signs. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Aged 18 to 60 years inclusive.
2. Allergy to birch pollen allergen, defined by:
• A positive case history of moderate to severe symptoms of seasonal allergic rhinoconjunctivitis ascribed to
birch pollen exposure that required repeated use of antihistamines, nasal steroids, and/or leukotriene
modifiers in at least the last 2 years;
• A positive skin prick test (SPT) for birch pollen allergen (wheals of ≥ 3 mm greater than the negative control
after skin prick testing) at Visit 1.
3. Positive SPT to histamine [wheal (longest diameter) ≥ 3 mm greater than the negative control].
4. Negative SPT to the negative control (redness with wheal ≤ 2 mm is acceptable).
5. Positive CPT at Visit 1
6. Forced expiratory volume (FEV) in 1 second (FEV1) ≥ 80% of predicted, with a FEV1/forced vital capacity (FVC) ratio ≥ 70%.
7. Adhere to the drug washout times prior to Screening (Visit 1 and 1a, if applicable). The use of other medications will be permitted if they are not expected to interfere with the ability of the subject to participate in the study and provided they have been on a stable regimen (i.e., the same dosage and administration) for 6 weeks prior to Screening.
8. Males or non-pregnant, non-lactating females
9. Normally active and otherwise judged to have an acceptable health status on the basis of medical history, physical examination and routine laboratory tests.
10. Willing and able to give written informed consent and must provide this consent.
11. Able to understand and comply with study instructions.
12. Willing and able to attend required study visits.
|
|
| E.4 | Principal exclusion criteria |
1. Any acute, chronic and/or infectious ocular disorder (other than allergic conjunctivitis)
which could interfere with the evaluation of the study medication.
2. Moderate to severe asthma, defined by:
• asthma requiring the daily use of controller medication or;
• emergency room visit or admission for asthma in the 12 months prior to Visit 1.
3. Presence of secondary alteration at the affected organ (i.e., emphysema, bronchiectasis,
nasal polyps, chronic sinusitis).
4. Any skin conditions which might interfere with the interpretation of the SPT results.
5. Current diagnosis of Type I diabetes. Subjects with Type II diabetes will only be allowed
to participate at the discretion of the Investigator.
6. Presence or history of auto-immune disease
7. History of cancer or concomitant illness (e.g., cardiovascular, pulmonary, metabolic,
renal, hepatic, gastrointestinal, dermatologic, venereal, hematologic, neurologic, or psychiatric diseases or disorders) that, in the opinion of the Investigator, would pose a safety risk or compromise the interpretation of efficacy for this birch immunotherapy.
8. Chronic use of inhaled, nasal, ocular, oral, intramuscular, intravenous, or potent or superpotent
topical corticosteroids (as assessed by the Investigator).
9. Chronic use of long acting antihistamines and other concomitant medications (e.g.,
tricyclic antidepressants) that would affect assessment of the effectiveness of study
drug(s).
10. Positive SPT [wheal (longest diameter) ≥ 3 mm greater than the negative control] at
Visit 1 to any of the following perennial allergens: house dust mites
(Dermatophagoides pteronyssinus and Dermatophagoides farinae), moulds (Alternaria
alternata), or epithelia (cat and dog) and positive case history of moderate to severe
symptoms to the aforementioned allergens during the 3 years prior to Visit 1
11. Positive SPT [wheal (longest diameter) ≥ 3mm greater than the negative control] at Visit 1 to grass pollen mix and positive case history of moderate to severe symptoms to the aforementioned allergens during the 3 years prior to Visit 1
12. Positive SPT [wheal (longest diameter) ≥ 3mm greater than the negative control] at
Visit 1 to any of the following autumn flowering plant allergens: mugwort (Artemisia
vulgaris), English plantain (Plantago lanceolata) or ragweed (Ambrosia sp.) and positive
case history of moderate to severe symptoms to the aforementioned allergens during
the 3 years prior to Visit 1
13. Any systemic disorder that could interfere with the evaluation of the study medication(s).
14. Acute or chronic infection or inflammation.
15. Upper or lower respiratory airway infection requiring antibiotics within 14 days of Visit 2
and a diagnosis of sinusitis within 30 days of Visit 2.
16. Manifest pulmonary or cardiac insufficiency.
17. Clinical history of allergy, hypersensitivity or intolerance to the excipients of the study
medication.
18. Clinical history of severe or life-threatening anaphylactic reactions to foods, insect
venom, exercise, drugs or idiopathic anaphylaxis.
19. Clinical history of immunodeficiency, including those who are on immunosuppressant
therapy.
20. Diseases with a pathogenesis interfering with the immune response and who have
received medication which could influence the results of the study.
21. Clinical history of recurrent idiopathic angioedema or hereditary angioedema.
22. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.
23. Beta-blocker medication, including eye drops, for any indication.
24. Unable to receive epinephrine therapy (i.e., use of epinephrine is contraindicated).
25. Clinical history of drug or alcohol abuse which would, at the Investigator’s discretion,
interfere with the subject’s participation in the study.
26. Clinically significant abnormal laboratory value that in the opinion of the Investigator
interferes with the results of the study or with the ability of the subject to participate in the
study.
27. Personal, financial or other dependent relationship (e.g. employee or immediate
relative) with the study site, Sponsor, Sponsor’s representative, or another individual
who has access to the clinical study protocol
28. Judicial or governmental detention, detainment or imprisonment in a public institution.
29. Have already undergone specific immunotherapy with the allergen to be investigated
or a cross-reacting allergen. An exception will be allowed if the prior immunotherapy was successful, symptoms reappeared some time after stopping the immunotherapy, and the immunotherapy was completed ≥ 5 years before Visit 1.
30. Treatment with a preparation containing MPL® within 6 months prior to Visit 1.
31. Participation in a clinical research study with a new chemical substance within 4 weeks of
Visit 1 or concomitantly with this study.
32. Unable or unwilling to cooperate with the Investigator and to comply with the protocol
requirements. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline to post-treatment in TSS following CPT |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Visit 2/2a (baseline) and Visit 8 (post-treatment) |
|
| E.5.2 | Secondary end point(s) |
Efficacy:
Proportion of subjects with negative CPT post-treatment
Number of additional allergen concentration steps required to elicit a positive CPT post-treatment
Change from baseline to post-treatment in individual symptom scores (ISS) following CPT
Immunological changes to immunoglobulins (birch specific IgG, IgG4 and IgE)
Safety:
Tolerability of different subcutaneous doses
Tolerability of cumulative subcutaneous doses (i.e. dose regimens)
Frequency of AEs
Frequency of ARCs (the total of treatment related injection site and systemic AEs experienced by a subject within a 24-hour period after an injection)
Premature discontinuation from treatment or study due to AEs
Clinical laboratory values (chemistry, haematology, urinalysis)
Vital signs
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy:
- Visit 8
- Visit 8
- V2/2a and V 8
- V 1 and V 8
Safety:
during the whole course of the study
|
|
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| dose-ranging (without reference product or placebo as comperator) |
|
| 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 |
| IMP in different cumulative doses |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 23 |
| 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
|
| The end of this study is defined as the date of the last 6 month follow up call of the last subject participating in the study. |
|
| 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 | 12 |
| 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 | 12 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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