Clinical trial NCT00264966: Multiple Dose ASM8 in Mild Asthmatics
Official title: A Double-blind, Placebo-controled, Crossover Study To Evaluate the Efficacy, Safety and Tolerability of Inhaled ASM8-003 in Subjects With Mild Allergic Asthma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Asthma
Keywords: Mild asthma
Lead sponsor: Syntara
Sponsor class: INDUSTRY
First posted: 2005-12-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To determine the safety and efficacy of multiple doses of ASM8 antisense oligonucleotides in asthmatics.

Detailed description: This is a double-blind, placebo-controlled, crossover trial to evaluate the safety, tolerability and efficacy of inhaled ASM8 for the treatment of allergen-induced asthma. Individuals with stable, mild to moderate allergic asthma by American Thoracic Society (ATS) criteria (1), with a history of episodic wheeze and shortness of breath, will be eligible for enrolment. The study is divided into 2 parts.

Eligibility criteria: Inclusion Criteria:

* Part 1: Men and women 18 to 65 years of age; generally good health; mild to moderate, stable, allergic asthma as defined by ATS criteria (1); history of episodic wheeze and shortness of breath; forced expiratory volume in 1 second (FEV1) at baseline ≥70% of the predicted value; able to comprehend and follow all required study procedures; willing and able to sign an informed consent form.

Part 2: Methacholine challenge at baseline (PC20 ≤16 mg/mL); positive skin-prick test to common aeroallergens (cat, dust mite, grass, pollen) and positive allergen-induced early and late airway bronchoconstriction.

Exclusion Criteria:

* Part 1 and Part 2: Significant acute or chronic medical or psychiatric illness; known coagulopathy, worsening of asthma or respiratory infection in the preceding 6 weeks; use of inhaled or oral corticosteroids within the last 28 days, antihistamines, immunosuppressives, nonsteroidal anti-inflammatory drugs, or anticoagulants (intermittent doses of short-acting β2-agonist are allowed); use of medications that may interact with ASM8; investigational drug use within 30 days; any clinically significant abnormality on screening laboratory determinations; current tobacco use in previous 3 months or 10 pack-years; pregnant or lactating women; women actively seeking pregnancy or who are not using adequate contraception; history of serious adverse effect (SAE) or hypersensitivity to any drug; 20% decrease in FEV1 or FVC with baseline saline in methacholine challenge during screening.

Primary outcomes:
measure: Comparison of the allergen-induced late asthmatic response (LAR) between ASM8 and placebo
Secondary outcomes:
measure: Evaluation of the safety and tolerability of ASM8.
measure: Comparison of the allergen-induced early asthmatic response (EAR) between ASM8 and placebo.
measure: Comparison of the allergen-induced airway hyperresponsiveness between ASM8 and placebo.
measure: Comparison of the allergen-induced changes in sputum eosinophils at 7 and 24 hours post allergen, between the ASM8 and placebo.
measure: Determination of the plasma and sputum pharmacokinetic profile of single- and repeated-doses of ASM8 in patients with mild asthma.
measure: Determination of the pharmacodynamic activity of ASM8 on specific gene expression, protein levels, differential cell counts, and eosinophilic cationic protein (ECP), as measured in sputum samples.
measure: Relief medication use in the ASM8 versus placebo
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Ste-Foy
country: Canada
facility: Hopital Laval
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Hospital
state: Saskatchewan
Study officials:
affiliation: McMaster University
name: Paul O'Byrne, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gauvreau GM, Boulet LP, Cockcroft DW, Baatjes A, Cote J, Deschesnes F, Davis B, Strinich T, Howie K, Duong M, Watson RM, Renzi PM, O'Byrne PM. Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. Am J Respir Crit Care Med. 2008 May 1;177(9):952-8. doi: 10.1164/rccm.200708-1251OC. Epub 2008 Jan 31.