E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Persistent allergic rhinitis or rhinoconjunctivitis with or without concomitant mild to moderate asthma induced by house dust mite (HDM) allergy (or sensitization). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
MedDRA Classification |
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 present study is to characterize the dose-response relationship of PM with a titrated nasal provocation test using four different PM doses in order to identify the optimal
dose in terms of highest clinical efficacy and safety. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent
2. Patients (male or female) must be ≥ 18 and ≤ 60 years at screening
3. Patients with allergic rhinitis or rhinoconjunctivitis for at least 1 year; allergic symptoms related to HDM, with or without concomitant clinically stable controlled mild to moderate asthma (according to GINA classification)
4. Patients with a history of concomitant asthma should have a FEV1 > 70% at inclusion. Patients without a history of asthma should have a FEV1 > 70% or a PEF > 80%.
5. Positive SPT to HDM D. pter and/or D. far (mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative, assessed within 1 year before randomization)
6. Serum specific IgE-test (ssIgE) level for HDM D. pter or D. far at screening (> 0.7 U/ml)
7. Positive TNPT for HDM D. pter extract at screening (Lebel score ≥ 6 at or below 10,000 AU/ml)
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E.4 | Principal exclusion criteria |
1. Current clinically relevant symptoms of seasonal rhinitis/rhinoconjunctivitis caused by other allergen(s) than HDM (with a demonstrated positive SPT for this allergen) at the time of inclusion (to avoid interference with TNPT at inclusion)
2. Patients sensitized to animals should not be included if they are symptomatic upon exposure and regularly exposed to animals
3. Completed allergen-specific immunotherapy (SCIT or SLIT) with HDM within the last 5 years
4. Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the past 5 years
5. Allergen-specific immunotherapy (SCIT or SLIT) with other allergens than HDM during the study period
6. Any vaccination one week before start of therapy and during the up-dosing phase
7. Any anti-IgE therapy within the last 6 months prior to inclusion and during study
8. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
9. Active malignancies or any malignant disease in the past 5 years
10. A chronic or acute disease that in the opinion of the investigator might place the patient at an additional risk, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, or hematological disorders
11. Moderate to severe nasal obstructive diseases such as polyps, septal deviations etc.
12. Clinically significant chronic sinusitis or ocular infection
13. Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma)
14. Use of systemic corticosteroids within 4 weeks of screening
15. Treatment with systemic or local -blockers
16. Participation in a clinical study with a new investigational drug within the last 3 months or a biological within the last 6 months prior to the study or during the study
17. Pregnancy, lactation or inadequate contraceptive measures (contraceptive measures considered as adequate include appropriate use of oral contraception, i.m. contraception or a contraceptive device)
18. Alcohol, drug, or medication abuse within the past year and during study
19. Any abnormal laboratory parameter at screening that in the opinion of the investigator is considered clinically relevant
20. Lack of co-operation or compliance
21. Severe psychiatric, psychological, or neurological disorders
22. Patients who are employees of the department, 1st grade relatives, or partners of the investigator
23. Expected changes in HDM exposure during the study (avoidance measures, move, etc.)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the absolute difference in mean symptom score in the TNPT between one year of treatment and baseline, among the different PM dose groups versus placebo. |
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E.5.2 | Secondary end point(s) |
• Absolute difference in mean symptom score in the TNPT between 22-30 weeks of treatment and baseline, among the different PM dose groups versus placebo.
• Average Adjusted Symptom Score (AdSS) measured during the last 8 weeks of treatment, among the different PM dose groups versus placebo (EMA Guideline, 2008; Grouin, 2011)
• Peak Nasal Inspiratory Flow (PNIF) measurements during the entire study period, among the different PM dose groups versus placebo
• Serum immunoglobulin levels measured at baseline, between 22 and 30 weeks and after approximately 1 year of treatment, among the different PM dose groups versus placebo
• Safety and tolerability among different PM dose groups versus placebo will be assessed during the entire study period by determination of PM related adverse events and by local and systemic reactions (reporting according to the Medical
Dictionary for Regulatory Affairs (MedDRA) (Cox, 2010) |
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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 | Information not present in EudraCT |
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.8.3 |
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 | 35 |
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |