Effects of AER 001 Administered by Nebulization on Antigen Challenge in Atopic Asthmatics

A Study To Investigate The Effects of AER 001 Administered by Nebulization on Antigen Challenge in Atopic Asthmatic Subjects

This is a single centre, double-blind, randomised, parallel group, repeated dose asthmatic subjects. Subjects will receive AER 001 (60 mgs) or placebo twice daily for 28 days. Before and after treatment subjects will be experimentally challenged with inhaled allergen to induce decreases in lung function. The primary outcome is late phase response to allergen as measured by the average percent change in FEV1 from 4-10 hours following allergen. Because AER 001 is a Th2 anti-inflammatory, it is hypothesized that AER 001 treatment will inhibit the late phase response to allergen challenge.

Study Overview

• Status: Completed
• Conditions: Allergic Asthma
• Intervention / Treatment: Drug: AER 001; Drug: placebo

Detailed Description

Objectives:

Primary Objective To investigate the effects of AER 001 on the late asthmatic response in mild to moderate asthmatics

Secondary Objectives

• To examine the effects of AER 001 on antigen induced airway hyperactivity to adenosine monophosphate and blood levels of circulating IgE.
• To characterise the pharmacokinetics of nebulised AER 001.

Exploratory Objectives

• To examine the effects of AER 001 on circulating sIL-13Rα2 and IFNgamma.
• To examine the results of single nucleotide polymorphism (SNP) analysis of IL-4, IL-13, IL-4Rα and IL-13R α to determine if there is any correlation between AER 001 response and genotype
• To examine levels of anti-AER 001 following administration of AER 001

Methodology:

• Single centre, double-blind, randomised, parallel group, repeated dose study in male and female asthmatic subjects.
• A sufficient number of subjects (at least 30 subjects) will be recruited to ensure that at least 26 completed sets of data will be obtained.
• Subjects will be randomised to receive either AER 001 60 mg / matched volume Placebo in a ratio of 1 active : 1 placebo ( block size of 6).
• Treatments will be administered by nebulization from a PARI LC Plus nebulizer
• Subjects are to receive b.i.d. administration of AER 001 / placebo for 27 days. A morning dose will be given on Day 28, (24 hours after Day 27 am-dose).

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Guy's Drug Research Unit, Quintiles, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Adult males and females > 18 years.

  • Subjects who if female, are not currently pregnant or breast feeding and are using medically acceptable methods of contraception.
  • Subjects who have a pre study medical history, physical examination, 12 Lead ECG acceptable to the investigator.
  • Subjects who have clinical laboratory tests within the reference ranges or clinically acceptable to the investigator.
  • Subjects who are negative for HbsAg, hepatitis C antibody and HIV II and I test at screening.
  • Subjects who are negative for drugs of abuse and alcohol tests at screening and admission.
  • Positive response on screening to a skin prick test.
  • Adenosine monophosphate PC20 on screening of ≥ 0.04 mg/ml
  • Subjects, who on the Allergen challenge, have a PC20 on allergen and exhibit a late phase response following the allergen challenge.
  • Subjects who have a FEV1 > 70% of predicted.
  • Subjects who have not received steroid treatment in the prior month.
  • Subjects who are non-smokers for at least 3 months prior to screening.
  • Have a < 10 pack year history.
  • Satisfies the Global Initiative in Asthma (GINA, 2002) definition of asthma or have been on treatment for asthma.
  • Subjects with stable, adequately treated medical conditions may be enrolled provided the Principal Investigator does not consider their study participation to place them at increased risk of adverse events. Subjects should continue their concomitant treatments without change during the study.
  • Subjects who are able and willing to give written informed consent.

Exclusion Criteria:

• • Subjects who do not conform to the above inclusion criteria.

  • Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders which would preclude antigen challenge.
  • Subjects who have a clinically relevant surgical history which would preclude antigen challenge.
  • Subjects who have a clinically relevant family history which would preclude antigen challenge.
  • Subjects who have a history of relevant drug hypersensitivity.
  • Subjects who have a history of alcoholism.
  • Subjects who have a history of drug abuse.
  • Subjects who consume more than 28 units (male)/ 21 units (female) of alcohol a week.

(unit = 1 glass of wine = 1 measure of spirits = ½ pint of beer)

• Subjects who have acute gastrointestinal symptoms at the time of screening and/or admission (e.g. nausea, vomiting, diarrhoea, heartburn)
• Subjects who have an acute respiratory infection such as influenza at the time of screening and/or admission.
• Female subjects who are not using an acceptable method of contraception.
• Subjects who have used any investigational drug and /or participated in any clinical trial within 3 months of their first dosing.
• Subjects using medication, which in the opinion of the Investigator will affect the outcome of the study.
• Subjects who have donated and/or received any blood or blood products within the previous 3 months prior to first dosing (to review on a case by case basis).
• Subjects who cannot communicate reliably with the investigator.
• Subjects who are unlikely to co-operate with the requirements of the study.
• Subjects who have previously taken AER 001

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; AER 001	Drug: AER 001; 60 mg (in nebuliser), twice daily for 28 days; Other Names: AEROVANT
Placebo Comparator: P; sterile saline	Drug: placebo; Sterile saline nebulised, twice daily for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To investigate the effects of AER 001 on the late asthmatic response in mild to moderate asthmatics as measured by average percent fall in FEV1 from 4-10 hours post allergen challenge (i.e. the late phase response)after 28 days of treatment	pre- vs. post 28 days of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary Objectives • To examine the effects of AER 001 on antigen induced airway hyperactivity to adenosine monophosphate and blood levels of circulating IgE. • To characterise the pharmacokinetics of nebulised AER 001.	pre- vs. post 28 days of treatment

Collaborators and Investigators

• Sponsor: Aerovance, Inc.
• Investigators: Principal Investigator: Darren Wilbraham, MD, Guy's Drug Research Unit, Quintiles Ltd.

Publications and helpful links

General Publications

• Slager RE, Hawkins GA, Ampleford EJ, Bowden A, Stevens LE, Morton MT, Tomkinson A, Wenzel SE, Longphre M, Bleecker ER, Meyers DA. IL-4 receptor alpha polymorphisms are predictors of a pharmacogenetic response to a novel IL-4/IL-13 antagonist. J Allergy Clin Immunol. 2010 Oct;126(4):875-8. doi: 10.1016/j.jaci.2010.08.001. No abstract available.

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: September 22, 2007
• First Submitted That Met QC Criteria: September 22, 2007
• First Posted (Estimate): September 26, 2007

Study Record Updates

• Last Update Posted (Estimate): September 26, 2007
• Last Update Submitted That Met QC Criteria: September 22, 2007
• Last Verified: September 1, 2007

More Information

Terms related to this study

• Keywords: Asthma; allergy; IL-13; IL-4; interleukin-4; interleukin-13
• 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: QGUY/2005/AER 001/-03; EUDRACT 2005-004829-26