Efficacy of TPI ASM8 During a 14-Day Allergen Challenge

A Double-Blind,Randomized, Placebo-controlled, 3-Way Cross Over Study to Evaluate the Efficacy and Safety of 14 Days TPI ASM8 in Subjects With Asthma

This is a randomized, double-blind, placebo-controlled, 3-way crossover trial to evaluate the efficacy and safety of two different doses of inhaled TPI ASM8 administered daily for 14 days for the treatment of allergic asthma and allergen-induced asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: TPI ASM8; Drug: TPI ASM8; Drug: TPI ASM8

Detailed Description

Two doses of TPI ASM8 will be compared to placebo and look at the effect on asthmatic responses after an allergen challenge during a 3-way cross over design. Sputum inflammation , mRNA gene expression on target receptors, ECP , biomarkers of mast cells activation et PK profile will be studied.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V4G5
    • Laval Centre de Pneumologie Chest Division
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Health Research Innovation Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Coastal Health Research Institute
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Mild asthma, male and female aged 18-55 y.old
• Steroid-naive, non-smoker
• Dual responders

Exclusion Criteria:

• Any chronic disease(unstable)
• Immunosuppressed, recent or ongoing steroid intake
• Methacholine PC 20 > 16 mg/mL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: TPI ASM8; ASM8 4mg/mL (low dose) daily for 14 days by inhalation; Drug: TPI ASM8; ASM8 4mg/mL (high dose) daily for 14 days by inhalation; Drug: TPI ASM8; Placebo PBS solution daily for 14 days by inhalation
ACTIVE_COMPARATOR: TPI ASM8 low dose	Drug: TPI ASM8; ASM8 4mg/mL (low dose) daily for 14 days by inhalation; Drug: TPI ASM8; ASM8 4mg/mL (high dose) daily for 14 days by inhalation; Drug: TPI ASM8; Placebo PBS solution daily for 14 days by inhalation
ACTIVE_COMPARATOR: TPI ASM8 high dose	Drug: TPI ASM8; ASM8 4mg/mL (low dose) daily for 14 days by inhalation; Drug: TPI ASM8; ASM8 4mg/mL (high dose) daily for 14 days by inhalation; Drug: TPI ASM8; Placebo PBS solution daily for 14 days by inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the AUC of the late asthmatic response (LAR) between treatments and placebo	The area under the curve fo the late asthmatic response(% fall in FEV1)(between 3-7 hrs post allergen challenge) will be compared between the 2 doses of TPI ASM8 and the placebo	Day 14 (Between 3-7 hr post-AIC)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the early and late asthmatic responses between active treatments and placebo after 14 days treatment	Compare the % fall in FEV1 during the EAR and the LAR post-allergen challenge on Day 14.	Day 14
Compare the Methacholine Hyperresponsiveness (PC20) between treatment pre and post allergen challenge	We will compare the PC20( provocative concentration of methacholine) that cause a 20% fall in FEV1	Day 13 and Day 15 (Pre & post AIC)
Effect of ASM8 on mast cells (as measured by specific biomarkers)	The leukotriene E4 and 9-11B PGF2 wil be measured in urine and plasma to determine the level of mast cells activation following the allergen challenge	Day 14 (pre, post and and peri-AIC)
Sputum inflammation indicators (Eos, neutrophils, etc.)	We will measure the levels of total cell counts and the differential to evaluate the degree of inflammation between treatments and placebo.	Day 14 and Day 15

Collaborators and Investigators

• Sponsor: Pharmaxis
• Investigators: Study Chair: Paul O'Byrne, MD, McMaster University; Study Director: Rene Pageau, M.Sc Pharm, Pharmaxis Ltd; Principal Investigator: Louis-Philippe Boulet, MD, Hopital Laval, Quebec; Principal Investigator: Gail M Gauveau, PhD, McMaster University; Principal Investigator: Mark Fitzgerald, MD, Vancouver Coastal Health Research Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: June 17, 2010
• First Submitted That Met QC Criteria: July 6, 2010
• First Posted (ESTIMATE): July 8, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): November 15, 2013
• Last Update Submitted That Met QC Criteria: November 14, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Mild to moderate asthma; Allergen inhalation challenge
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: TPI ASM8-207