A Pilot Study of the Treatment of Eosinophilic Esophagitis With Omalizumab

• Sponsor: University of Utah (Other)
• Overall Status: Completed
• CT.gov ID: NCT00123630
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Eosinophilic esophagitis (EE) is an increasingly recognized condition characterized by dysphagia, food impaction or other obstructive esophageal symptoms in children and young adults.

The pathophysiology of EE appears to be an allergy/atopy mediated disease. A personal and family history of allergic diseases (food allergies, atopic dermatitis, asthma, allergic rhinitis or conjunctivitis) has been noted in 62-85% of patients with EE. The rising incidence of EE may be related to the worldwide allergy and asthma epidemic.

Current treatment of EE is directed at decreasing esophageal allergic inflammation. Oral and topical corticosteroids, cromolyn sodium, montelukast and elemental/elimination diets have all been shown to be effective. However, none of these treatments are directed at the specific pathophysiologic mechanism of EE and some have significant side effects.

The shared pathogenetic mechanisms of EE and asthma suggest that therapeutic strategies directed at asthma may also be effective for EE. Specifically those targeted at the allergic immune mechanisms involved with asthma may be effective. Omalizumab is a recently developed anti-IgE antibody that has been shown to decrease the use of inhaled and oral corticosteroids, reduce the frequency of asthma exacerbations, and improve asthma related symptoms in patients with allergic asthma. The objective of the study is to determine the efficacy of omalizumab in the treatment of eosinophilic esophagitis

Condition or Disease	Intervention/Treatment	Phase
Esophagitis	Drug: omalizumab; Drug: Placebo	Phase 2

Detailed Description

This is a dual-center double-blind, placebo controlled trial of omalizumab for the treatment of EE. Omalizumab will be dosed depending on the patient's body weight and baseline IgE level. Omalizumab or placebo will be administered subcutaneously every 4 weeks for 16 weeks. At study entry subjects will have EGD with biopsies performed to ensure the diagnosis and obtain tissue for histologic analysis. No dilation will be performed at this time. Baseline validated questionnaires for dysphagia, GERD, and atopy will also be administered. Blood will be drawn for baseline serum testing. Repeat questionnaires and rating of overall symptom improvement will be administered at 4 week intervals for the rest of the study period. At the end of the 16 week period, repeat endoscopy will be performed and biopsies taken. Esophageal dilation may be performed if clinically indicated at this time. Blood will also be drawn for repeat serum testing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of the Treatment of Eosinophilic Esophagitis With Omalizumab
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo placebo group	Drug: Placebo; Placebo given IV once every 2-4 weeks based on weight; Other Names: saline
Experimental: omalizumab Xolair group	Drug: omalizumab; omalizumab dosed IV based on IgE level and weight every 2 - 4 weeks; Other Names: Xolair

Outcome Measures

Primary Outcome Measures

1. Change in Eosinophil Numbers Per High Power Field Proximally and Distally Between Baseline and Post-treatment and Between Both Groups [16 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female subjects aged 12-60 years of age with EE as defined above

• Serum IgE level 30-700 IU/mL

• Subjects with acceptable medical history, physical exam and laboratory test results

• No history of bleeding diathesis, significant cardiopulmonary disease, or other contraindication to upper endoscopy

Exclusion Criteria:

• Need for esophageal dilation at enrollment due to food impaction or inability to pass endoscope

• Inability of subject to provide informed consent (if ages 18-60), or inability of children (ages 12-17) to provide assent

• History of esophagogastric surgery

• Presence of other esophageal pathology that could account for patients' symptoms including eosinophil infiltration due to gastroesophageal reflux disease (GERD)

• Incarceration

• Pregnancy

• Women of childbearing potential not using the contraception method(s)

• Patients with elevated serum IgE levels for reasons other than atopy

• Patients taking cromolyn sodium or nedocromil sodium within 1 month of visit 1

• Patients taking oral or topical corticosteroids within one month of visit 1

• Patients taking leukotriene receptor inhibitors within one month of visit 1

• Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study

• Patients with a history of noncompliance to medical regimens or who were considered potentially unreliable

• Use of any other investigational agent in the last 30 days

• Patients with a known hypersensitivity to any ingredient of rhuMAb-E25, study rescue medication

• Patients with Barrett's esophagus will be excluded if found endoscopically or pathologically at biopsy

• Currently treated with omalizumab or treated with omalizumab within the past 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Utah HSC	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

• University of Utah
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: John C. Fang, M.D., University of Utah HSC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John C. Fang, M.D., Principal Investigator, University of Utah
• ClinicalTrials.gov Identifier: NCT00123630
• Other Study ID Numbers: 13623
• First Posted: Jul 25, 2005
• Last Update Posted: May 20, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by John C. Fang, M.D., Principal Investigator, University of Utah: eosinophilic esophagitis; omalizumab
• Additional relevant MeSH terms: Esophagitis; Eosinophilic Esophagitis; Omalizumab

Study Results

Participant Flow

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo 150 to 375 mg is administered SC every 2 or 4 weeks. Because the solution is slightly viscous, the injection may take 5-10 seconds to administer. Doses (mg) and dosing frequency are determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg).	Xolair (Omalizumab)150 to 375 mg is administered SC every 2 or 4 weeks. Because the solution is slightly viscous, the injection may take 5-10 seconds to administer. Doses (mg) and dosing frequency are determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg).
Period Title: Overall Study
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Omalizumab	Total
Arm/Group Description	Placebo 150 to 375 mg is administered SC every 2 or 4 weeks. Because the solution is slightly viscous, the injection may take 5-10 seconds to administer. Doses (mg) and dosing frequency are determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg).	Xolair (Omalizumab)150 to 375 mg is administered SC every 2 or 4 weeks. Because the solution is slightly viscous, the injection may take 5-10 seconds to administer. Doses (mg) and dosing frequency are determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg).	Total of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	15 100%	30 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28 (6)	32 (12)	30 (10)
Sex: Female, Male (Count of Participants)
Female	5 33.3%	3 20%	8 26.7%
Male	10 66.7%	12 80%	22 73.3%
Region of Enrollment (participants) [Number]
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Change in Eosinophil Numbers Per High Power Field Proximally and Distally Between Baseline and Post-treatment and Between Both Groups
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

The analysis was per protocol. There were no subjects who were withdrawn or lost to follow-up in this study.

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo 150 to 375 mg is administered SC every 2 or 4 weeks. Because the solution is slightly viscous, the injection may take 5-10 seconds to administer. Doses (mg) and dosing frequency are determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg).	Xolair (Omalizumab)150 to 375 mg is administered SC every 2 or 4 weeks. Because the solution is slightly viscous, the injection may take 5-10 seconds to administer. Doses (mg) and dosing frequency are determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg).
Measure Participants	15	15
Number [perecentage of eos per high power field]	0.6	-7.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Placebo		Omalizumab
Arm/Group Description	Placebo 150 to 375 mg is administered SC every 2 or 4 weeks. Because the solution is slightly viscous, the injection may take 5-10 seconds to administer. Doses (mg) and dosing frequency are determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg).		Xolair (Omalizumab)150 to 375 mg is administered SC every 2 or 4 weeks. Because the solution is slightly viscous, the injection may take 5-10 seconds to administer. Doses (mg) and dosing frequency are determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg).
All Cause Mortality
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)

Limitations/Caveats

small numbers enrolled

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.