AQUA: A Study of Omalizumab in the Prevention of Allergen Induced Airway Obstruction in Adults With Mild Allergic Asthma

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00434434
• Collaborator: (none)
• Enrollment: 61
• Arms: 3
• Duration (Months): 20

Study Details

Study Description

Brief Summary

This was a multicenter, randomized, double-blind, parallel-group, three-arm, placebo-controlled study designed to demonstrate the efficacy of two different formulations of omalizumab compared with placebo in reducing the airway reaction to an inhaled aeroallergen solution in adult subjects with mild allergic asthma.

Condition or Disease	Intervention/Treatment	Phase
Allergic Asthma	Drug: omalizumab; Drug: omalizumab; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lyophilized and Aged Liquid Omalizumab in the Prevention of Allergen-Induced Airway Obstruction in Adults With Mild Allergic Asthma
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: omalizumab; Aged Liquid; subcutaneous repeating dose
Experimental: 2	Drug: omalizumab; Lyophilized; subcutaneous repeating dose
Placebo Comparator: 3	Drug: placebo; Subcutaneous repeating dose

Outcome Measures

Primary Outcome Measures

1. Change in Logarithmically Transformed (log2) Allergen PC15 Concentration (Allergen Concentration Required to Evoke a 15% Decrease in FEV1) [From baseline to Week 16]

   The primary analysis included two tests: a test for superiority of the lyophilized formulation of omalizumab compared with placebo in the change of allergen concentration and a test for the superiority of the aged liquid omalizumab compared with placebo. The difference for the change in the allergen concentration between the lyophilized formulation of omalizumab and placebo, and between the aged liquid omalizumab and placebo were assessed by the exact Wilcoxon-Mann-Whitney test.

Secondary Outcome Measures

1. Ratio of the Allergen Forced Expiratory Volume at One Second (FEV1) Two-point Slope at the Week 16 Allergen Challenge to the Allergen FEV1 Two-point Slope at the Baseline Allergen Challenge [From baseline to Week 16]

   FEV1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity, measured in liters. The allergen FEV1 two-point slope is defined as the final percent change in FEV1 from pre-challenge value divided by the final value of allergen concentration used in the challenge.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed Informed Consent Form

• Meet criteria for the diagnosis of allergic asthma

• Be between the ages of 18 to 65 years

• Have a normal chest X-ray within 2 years of screening

Exclusion Criteria:

• Need daily controller medication for asthma

• History of hypersensitivity to the study drug or to drugs with similar chemical structures or to any ingredients, including excipients of the study medication or drugs related to omalizumab (e.g., monoclonal antibodies, polyclonal gamma globulin)

• Have a documented medical history of anaphylaxis

• Have lung disease other than mild allergic asthma

• Have taken other investigational drugs within 30 days or 5 half-lives prior to the screening visit, whichever is longer

• Are unable or unwilling to comply with study procedures and visits

• Are pregnant or lactating

• Have significant medical illness other than asthma, including malignancies, parasitic infections, immune system disorders, and thrombocytopenia

• Have been treated with omalizumab within 12 months prior to screening

• Currently smoke or have a history of smoking more than 10 pack-years

• Have a history of drug or alcohol abuse, which, in the judgment of the investigator, may put the subject at risk for being unable to participate fully in the study for the duration of the study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Dennis Wong, M.D., Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00434434
• Other Study ID Numbers: Q4160g
• First Posted: Feb 13, 2007
• Last Update Posted: May 26, 2010
• Last Verified: Apr 1, 2010

• Keywords provided by , ,: AQUA; anti-CD11; CD11a; Asthma; Allergy
• Additional relevant MeSH terms: Asthma; Airway Obstruction; Omalizumab; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Liquid Omalizumab	Lyopholized Omalizumab	Placebo
Arm/Group Description	Liquid omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Lyophilized omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Lyophilized placebo subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening
Period Title: Overall Study
STARTED	23	24	14
COMPLETED	21	24	13
NOT COMPLETED	2	0	1

Baseline Characteristics

Arm/Group Title	Liquid Omalizumab	Lyopholized Omalizumab	Placebo	Total
Arm/Group Description	Liquid omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Lyophilized omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Lyophilized placebo subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Total of all reporting groups
Overall Participants	23	24	14	61
Age, Customized (participants) [Number]
18 to 40 years	18 78.3%	21 87.5%	11 78.6%	50 82%
41 to 65 years	5 21.7%	1 4.2%	3 21.4%	9 14.8%
> 65 years	0 0%	2 8.3%	0 0%	2 3.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.5 (10.3)	30.6 (12.8)	32.0 (9.6)	30.1 (11.1)
Sex: Female, Male (Count of Participants)
Female	10 43.5%	8 33.3%	10 71.4%	28 45.9%
Male	13 56.5%	16 66.7%	4 28.6%	33 54.1%

Outcome Measures

1. Primary Outcome

Title	Change in Logarithmically Transformed (log2) Allergen PC15 Concentration (Allergen Concentration Required to Evoke a 15% Decrease in FEV1)
Description	The primary analysis included two tests: a test for superiority of the lyophilized formulation of omalizumab compared with placebo in the change of allergen concentration and a test for the superiority of the aged liquid omalizumab compared with placebo. The difference for the change in the allergen concentration between the lyophilized formulation of omalizumab and placebo, and between the aged liquid omalizumab and placebo were assessed by the exact Wilcoxon-Mann-Whitney test.
Time Frame	From baseline to Week 16

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (ITT) population

Arm/Group Title	Liquid Omalizumab	Lyopholized Omalizumab	Placebo
Arm/Group Description	Liquid omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Lyophilized omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Lyophilized placebo subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening
Measure Participants	22	23	13
Median (Full Range) [concentration change]	1.15	1.85	0.36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liquid Omalizumab, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	exact Wilcoxon-Mann-Whitney

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lyopholized Omalizumab, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0133
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	exact Wilcoxon-Mann-Whitney

2. Secondary Outcome

Title	Ratio of the Allergen Forced Expiratory Volume at One Second (FEV1) Two-point Slope at the Week 16 Allergen Challenge to the Allergen FEV1 Two-point Slope at the Baseline Allergen Challenge
Description	FEV1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity, measured in liters. The allergen FEV1 two-point slope is defined as the final percent change in FEV1 from pre-challenge value divided by the final value of allergen concentration used in the challenge.
Time Frame	From baseline to Week 16

Outcome Measure Data

Analysis Population Description

Modified ITT population

Arm/Group Title	Liquid Omalizumab	Lyopholized Omalizumab	Placebo
Arm/Group Description	Liquid omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Lyophilized omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening	Lyophilized placebo subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening
Measure Participants	22	23	13
Median (Full Range) [ratio of FEV1]	0.52	0.29	0.95

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liquid Omalizumab, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	exact Wilcoxon-Mann-Whitney

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lyopholized Omalizumab, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0028
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	exact Wilcoxon-Mann-Whitney

Adverse Events

Adverse Event Reporting Description	Safety evaluable population
Arm/Group Title	Liquid Omalizumab		Lyopholized Omalizumab		Placebo
Arm/Group Description	Liquid omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening		Lyophilized omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening		Lyophilized placebo subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening
All Cause Mortality
	Liquid Omalizumab		Lyopholized Omalizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Liquid Omalizumab		Lyopholized Omalizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		2/24 (8.3%)		0/14 (0%)
General disorders
Pyrexia	0/23 (0%)		1/24 (4.2%)		0/14 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	0/23 (0%)		1/24 (4.2%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Liquid Omalizumab		Lyopholized Omalizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/23 (30.4%)		6/24 (25%)		5/14 (35.7%)
General disorders
Chest Discomfort	0/23 (0%)		1/24 (4.2%)		1/14 (7.1%)
Facial Pain	0/23 (0%)		0/24 (0%)		1/14 (7.1%)
Infections and infestations
Nasopharyngitis	3/23 (13%)		2/24 (8.3%)		1/14 (7.1%)
Upper Respiratory Tract Infection	2/23 (8.7%)		0/24 (0%)		2/14 (14.3%)
Injury, poisoning and procedural complications
Joint Dislocation	1/23 (4.3%)		0/24 (0%)		1/14 (7.1%)
Concussion	0/23 (0%)		0/24 (0%)		1/14 (7.1%)
Contusion	0/23 (0%)		0/24 (0%)		1/14 (7.1%)
Joint Injury	0/23 (0%)		0/24 (0%)		1/14 (7.1%)
Nervous system disorders
Headache	2/23 (8.7%)		2/24 (8.3%)		0/14 (0%)
Sinus Headache	0/23 (0%)		0/24 (0%)		1/14 (7.1%)
Psychiatric disorders
Middle Insomnia	0/23 (0%)		0/24 (0%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/23 (4.3%)		1/24 (4.2%)		1/14 (7.1%)
Oropharyngeal Pain	1/23 (4.3%)		1/24 (4.2%)		1/14 (7.1%)
Cough	0/23 (0%)		0/24 (0%)		1/14 (7.1%)
Dyspnoea	0/23 (0%)		0/24 (0%)		1/14 (7.1%)
Skin and subcutaneous tissue disorders
Periorbital Oedema	0/23 (0%)		0/24 (0%)		1/14 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.