E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients suffering from allergic rhinitis/rhinoconjunctivitis related to grass pollen (with or without concomitant mild to moderate persistent asthma). |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001723 |
E.1.2 | Term | Allergic rhinitis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal 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 |
Primary Objective:
Determination of the optimal effective dose of SUBLIVAC FIX Phleum pratense based on reduction of upper airways reactivity assessed by TNPT after 5 months of treatment with different dosages of SUBLIVAC FIX Phleum pratense compared to placebo.
Co-primary Objective:
Difference in proportions of patients not reaching maintenance dose within 10 days due to related AEs of different dosages of SUBLIVAC FIX Phleum pratense compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
- Safety and tolerability of different dosages of SUBLIVAC FIX Phleum pratense compared to placebo assessed by local and systemic reactions.
- Changes in serum specific immunoglobulin levels after 5 months of treatment with different dosages of SUBLIVAC FIX Phleum pratense compared to placebo.
- Changes in PNIF after 5 months of treatment with different dosages of SUBLIVAC FIX Phleum pratense compared to placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent
2. Age ≥18 ≤ 60 years
3. Allergic rhinitis/rhinoconjunctivitis related to grass pollen with or without concomitant mild to moderate persistent asthma
4. FEV1>70% for patients with a history of asthma, FEV>70% or PEF>80% for patients without a history of asthma
5. A positive SPT (mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) for grass pollen assessed within 1 year before randomization.
6. Positive serum specific anti-grass IgE-test (>0.7 U/mL)
7. A positive TNPT for grass pollen at screening (Lebel score ≥6) at ≤10,000 AU/mL
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E.4 | Principal exclusion criteria |
1. Patients with (expected) clinically relevant symptoms during the course of the trial due to concomitant sensitization i.e. positive SPT (mean wheal diameter ≥ 3mm) to allergens other than grass pollen
2. Patients sensitized to pets should not be included if they are regularly exposed to pets and are symptomatic upon exposure to pets
3. Completed immunotherapy (SCIT or SLIT) with grass pollen allergens within the past 5 years
4. Completed unsuccessful specific immunotherapy in the past
5. Vaccination within one week before start of therapy or during the initiation phase
6. Anti-IgE therapy within the 6 months prior to inclusion and during the study
7. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
8. Active malignancies or any malignant disease during the previous 5 years
9. Severe uncontrolled diseases that could increase the risk for patients participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or haematological disorders
10. Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study
11. Moderate to severe nasal obstructive diseases that preclude a TNPT (septal deviation, nasal polyps, recent nasal surgery, etc.)
12. Diseases with a contraindication for the use of Adrenaline (e.g. hyperthyroidism, glaucoma)
13. Use of systemic steroids within 4 weeks before start of the study and during the study
14. Treatment with systemic and local β-blockers
15. Participation in a clinical study with a new investigational drug within the last 3 months or for a biological within the last 6 months prior to or during the study
16. Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or –pill)
17. Alcohol, drug or medication abuse within the past year
18. Any clinically significant abnormal laboratory parameter at screening
19. Lack of cooperation or compliance
20. Severe psychiatric, psychological, or neurological disorders
21. Patients who are employees of the institution or 1st grade relatives or partners of the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the absolute difference in mean total symptom score in the TNPT between 5 months of treatment and baseline. The differences in mean symptom score of the active dose groups and placebo will be compared in a step-down pairwise comparison starting with the highest dose.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint for primary end point - after 5 months of treatment.
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E.5.2 | Secondary end point(s) |
Safety and tolerability of different dosages of SUBLIVAC FIX Phleum pratense vs. placebo will be assessed by number and severity of immediate and delayed local and systemic reactions.
Immunogenicity of different dosages of SUBLIVAC FIX Phleum pratense (vs. placebo) after 5 months of treatment will be determined by serum specific immunoglobulin levels. At baseline and the end of the study visit a blood sample will be drawn for determination of specific IgE, IgG and IgG4 to grass. Changes in specific immunoglobulin levels before and after 5 months of treatment will be determined
Changes in PNIF as a parameter of nasal patency will be determined following TNPT in patients receiving different dosages of SUBLIVAC FIX Phleum pratense compared to placebo
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 5 months 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 | No |
E.6.3 | Therapy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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
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Work of investigators with study data is ending by answering last queries.
Thus, end of clinical trial was defined as Database lock.
In general, following prerequisites for database lock are given:
- Queries returned, processed and entered
- Coding completed/reviewed
- Review of data by statistician (protocol violations, relevant adverse events)
- All automatic batches related to study deactivated
When these requirements are fulfilled it is considered as end of clinical part. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |