| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Seasonal Allergic Rhinitis (sensitivity to Timothy grass pollen) | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10039776 | | E.1.2 | Term | Seasonal allergic rhinitis | |
| 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 | | To assess the effects of Imatinib on allergic inflammation following repeated nasal allergen challenge (NAC) in subjects with seasonal allergic rhinitis sensitive to Timothy grass pollen – in particular to assess if Imatinib reduces mast cell degranulation (measured by β-tryptase and PGD2) in response to allergen challenge | |
| E.2.2 | Secondary objectives of the trial | Additional markers of inflammation will also be measured following NAC:
- Enumeration of eosinophils in nasal lavage following nasal allergen challenge
- Total nasal symptom score (TNSS) following nasal allergen challenge
- Soluble mediators collected from adsorption onto nasal filter papers following nasal allergen challenge, with a focus on Th2-associated cytokines (to include IL-4, IL-5 and IL-13)
Exploratory objective:
To perform exploratory pharmacogenetic assessments to examine whether individual genetic variation in genes relating allergic disease correlate with systemic levels of allergic mediators.
| |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Healthy male non-smoking subjects age 18 to 55 years of age included, and in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at screening.
2. Subjects must have a history of seasonal allergic rhinitis consistent with Timothy grass pollen allergy. They must show:
- a positive skin prick test to Timothy grass pollen (wheal difference Timothy grass pollen – negative control ≥ 3 mm) at or within the 12 months preceding the screening visit and
- demonstrate symptomatic worsening (TNSS ≥4) within one hour after nasal allergen challenge
3. Be otherwise healthy with no health problems that may jeopardize the subjects
participating in the study, absence of history of other significant allergies. Subjects must weigh at least 50 kg.
4. Able to communicate well with the investigator, to understand and comply with the
requirements of the study. Understand and sign the written informed consent.
5. Subjects and their partners must agree to use effective contraceptive measures from screening until the end of study visit.
| |
| E.4 | Principal exclusion criteria | 1. Smokers (use of tobacco products in the previous 3 months).
2. Presence of any respiratory disease other than a history of mild stable asthma not requiring treatment and associated with normal lung function (FEV1 ≥80% predicted at screening).
3. Presence of any structural nasal abnormalities or nasal polyps on examination, a history of frequent nose bleeding, recent nasal surgery or recent (within 8 weeks prior to screening visit) or recent (four weeks) or ongoing upper or lower respiratory tract infection.
4. Use of any medication that would affect the response to the allergen challenge (e.g. corticosteroids, decongestants, anti-histamines, medications with anti-inflammatory effects) or any other nasally applied medication within 14 days prior to allergen challenge (30 days for systemic anti-inflammatory therapy including oral corticosteroids), or known to influence Imatinib bioavailability or clearance (see Section 6.3 of [Investigators Brochure, Ed. 8]).
5. History of allergy to imatinib.
6. Significant illness within two weeks prior to screening.
7. A past medical history of inherited heart disease, valve defect, cardiomyopathy, rheumatic fever, arrhythmias, cardia interventions or clinically significant ECG abnormalities.
8. History or laboratory evidence of acute or chronic renal insufficiency or abnormal liver function.
9. History of immunodeficiency diseases or blood borne infectious disease, including a HIV or Hepatitis B surface antigen (HBsAg) or Hepatitis C test
10. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations.
11. Donation or loss of 400 ml or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation.
12. Inability to use inhaled or oral medications or for any other reason deemed unable to participate in the opinion of the study investigators. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | To assess if Imatinib reduces mast cell degranulation (measured by β-tryptase and PGD2) in response to allergen challenge | |
| 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 | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Yes |
| 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 | | Efficacy and Safety in different Indication | |
| 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 | | the positive control medicinal product is open label | |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| 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 | Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 1 |
| 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 | 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
