An exploratory study of the effects of Imatinib on allergic inflammation following out of allergy season repeated nasal allergen challenge in subjects with seasonal allergic rhinitis sensitive to Timothy grass pollen – an exploratory study of c-kit inhibition in allergic respiratory diseases

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2006-004722-82-GB
• Date of registration: 22/11/2006
• Prospective Registration: No
• Primary sponsor: Novartis Pharma Services AG
• Public title: An exploratory study of the effects of Imatinib on allergic inflammation following out of allergy season repeated nasal allergen challenge in subjects with seasonal allergic rhinitis sensitive to Timothy grass pollen – an exploratory study of c-kit inhibition in allergic respiratory diseases
• Scientific title: An exploratory study of the effects of Imatinib on allergic inflammation following out of allergy season repeated nasal allergen challenge in subjects with seasonal allergic rhinitis sensitive to Timothy grass pollen – an exploratory study of c-kit inhibition in allergic respiratory diseases
• Date of first enrolment: 20/11/2006
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004722-82
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: the positive control medicinal product is open label If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Seasonal Allergic Rhinitis (sensitivity to Timothy grass pollen)
MedDRA version: 8.1 Level: LLT Classification code 10039776 Term: Seasonal allergic rhinitis

Intervention(s)

Trade Name: Glivec 100 mg capsules, hard
Product Code: STI571
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Imatinib
CAS Number: 152459-95-5
Current Sponsor code: STI517
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Flixonase Aqueous Nasal Spray
Pharmaceutical Form: Nasal spray*
INN or Proposed INN: Fluticasone
CAS Number: 80474-14-2
Concentration unit: % (W/W) percent weight/weight
Concentration type: equal
Concentration number: 0.05-

Primary Outcome(s)

Secondary Objective: 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.

Main Objective: 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 ß-tryptase and PGD2) in response to allergen challenge

Primary end point(s): To assess if Imatinib reduces mast cell degranulation (measured by ß-tryptase and PGD2) in response to allergen challenge

Secondary ID(s)

CSTI571E2204