Effects of Imatinib in Subjects With Seasonal Allergic Rhinitis and Who Are Sensitive to Timothy Grass Pollen

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

This study will assess the effects of Imatinib on allergic inflammation following repeated nasal allergen challenge in subjects with seasonal allergic rhinitis sensitive to Timothy grass pollen.

Study Overview

• Status: Completed
• Conditions: Seasonal Allergic Rhinitis
• Intervention / Treatment: Drug: Imatinib

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Horsham, United Kingdom
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male non-smoking subjects aged 18-55 years, with 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
• Be otherwise healthy with no health problems that may jeopardize the subjects participating in the study, absence of history of other significant allergies.
• Subjects and their partners must agree to use effective contraceptive measures from screening until the end of study visit.

Exclusion Criteria:

• Respiratory disease other than a history of mild stable asthma not requiring treatment and associated with normal lung function.
• Structural nasal abnormalities or nasal polyps on examination, a history of frequent nose bleeding, recent nasal surgery or recent (within 8 weeks prior to baseline visit) or recent (four weeks) or ongoing upper or lower respiratory tract infection.
• 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
• History or laboratory evidence of acute or chronic renal insufficiency or abnormal liver function.
• Subjects may voluntarily withdraw from or be withdrawn from the study at the discretion of the investigator or the sponsor at any time. Subjects may be withdrawn from the study prematurely for one of the following reasons:
• Subject withdrew consent
• Upper respiratory tract infection
• Presence of allergic rhinitis symptoms in the screening period or prior to pre-wash on Day 1
• A past medical history of inherited heart disease, valve defect, cardiomyopathy, rheumatic fever, arrhythmias, cardiac interventions or clinically significant ECG abnormalities.
• Adverse events and non-tolerable symptoms resulting from allergen challenge
• Administration of a concomitant medication (other than those randomized to receive Fluticasone propionate) that would impact on the study results (e.g. corticosteroids), including any subjects requiring asthma therapy (inhaled or systemic).

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Effect of Imatinib on the reduction of mast cell degranulation (measured by β-tryptase and PGD2) in response to allergen challenge

Secondary Outcome Measures

Outcome Measure
Additional markers of inflammation following nasal allergen challenge (NAC):
Enumeration of eosinophils in nasal lavage following NAC
Total nasal symptom score (TNSS) following NAC
Soluble mediators collected from adsorption onto nasal filter papers following NAC, with a focus on Th2-associated cytokines

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion: December 7, 2022
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: January 23, 2007
• First Submitted That Met QC Criteria: January 23, 2007
• First Posted (Estimate): January 24, 2007

Study Record Updates

• Last Update Posted (Estimate): November 19, 2007
• Last Update Submitted That Met QC Criteria: November 16, 2007
• Last Verified: November 1, 2007

More Information

Terms related to this study

• Keywords: Imatinib, allergic inflammation, out of allergy season, repeated nasal allergen, seasonal allergic rhinitis, sensitive, Timothy grass pollen, c-kit inhibition
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Nose Diseases; Hypersensitivity; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: CSTI571E2204

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No