Efficacy and Safety of Omalizumab in Bullous Pemphigoid - Full Text View

Sponsors and Collaborators:	University of Iowa Genentech
Information provided by:	University of Iowa
ClinicalTrials.gov Identifier:	NCT00472030

Purpose

The primary objective is to test the safety and efficacy of Xolair in the treatment of the autoimmune blistering disease, bullous pemphigoid (BP).

This is a pilot, open label case-control study. Patients treated with Xolair will be compared to patients receiving standard treatment with prednisone.

The enrollment period for the study is 24 weeks: 16 weeks active treatment and 8 additional weeks of observation.

Condition	Intervention	Phase
Bullous Pemphigoid	Drug: omalizumab Drug: prednisone	Phase IV

MedlinePlus related topics: Pemphigus

Drug Information available for: Prednisone Omalizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	An Open Label Case Series on the Effects of Xolair (Omalizumab) in Bullous Pemphigoid

Further study details as provided by University of Iowa:

Primary Outcome Measures:

Assessment of total and new blister numbers over the 16 week period. Time to the cessation of new blister formation. The total dose of prednisone (mg/kg/d) during the 16 week treatment period. Parameters will be compared to the controls. [ Time Frame: 24 total weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Circulating anti-BMZ autoantibodies by indirect immunofluorescence. Measure collagen XVII-specific IgE and IgG autoantibodies present in the sera of these patients at day 0, week 1,2,4,8,12,16, and 24. Specific antibodies will be measured by ELISA. [ Time Frame: 24 total weeks ] [ Designated as safety issue: No ]
An additional secondary assessment will be the number of circulating eosinophils and the ability of the patients' autoantibodies to trigger histamine release. These will be measured at the same time-points as the autoantibody measures. [ Time Frame: 24 total weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	August 2007
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Omalizumab treatment.	Drug: omalizumab Subcutaneous administration of omalizumab, dose dependent on weight and circulating levels of IgE. Omalizumab will be administered every 4 weeks for 12 weeks. Additional injections will be given on weeks 2,6,10 and 14 if required based on weight and IgE levels.
2: Active Comparator The control arm of the study will receive standard prednisone therapy to a maximum dose of 0.5 mg/kg/day.	Drug: prednisone Prednisone, to a maximum dose of 0.5 mg/kg/day.

Detailed Description:

Objectives: The primary objective is to test the safety and efficacy of Xolair in the treatment of the autoimmune blistering disease, bullous pemphigoid (BP).

Study Rationale: The current treatment for BP is non-specific immunosuppression, causing great morbidity in these patients. Recently, pathogenic IgE class autoantibodies have been identified in these patients. Development of a more targeted approach to treatment may reduce morbidity.

Methodology: This is a pilot, open label case-control study. Patients treated with Xolair will be compared to patients receiving standard treatment with prednisone.

Number of centers & patients: This is a single center study that will enroll 12 patients.

Population: Bullous pemphigoid patients, meeting clinical, histological and immunologic criteria for the disease will be enrolled. Pregnant women, children < 18, and patients unable to give consent will be excluded from this preliminary study.

Investigational drug: Xolair® (Omalizumab)

Study duration: 24 weeks: 16 weeks active treatment, 8 additional weeks of observation

Evaluation criteria: Primary: 1. Time to cessation of new blister formation. 2. Percent body surface involved before and after treatment 3. Total and average daily dose of prednisone required in 30, 60 and 180 days after starting Xolair. Secondary: 1. circulating eosinophils 2. Measurement of circulating anti-BMZ (basement membrane zone) autoantibodies 3. Histamine release assay.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have the clinical and histological findings consistent with bullous pemphigoid. Clinically this is defined as urticarial plaques and/or vesicles and bullae. Histologically patients must show characteristic eosinophilic spongiosis and/or subepidermal separation of the skin consistent with BP.
Patients must have either a positive direct (IgG and/or C3 at the BMZ) or indirect (IgG on the roof of salt-split skin) immunofluorescence microscopy features of pemphigoid.
Patients of both sexes, all races and ethnic backgrounds that are 18 years of age or older will be eligible to participate in this study.
Patients much have more than 5% total body surface involved, since patients with less extensive disease are often treated with topical measures only.

Exclusion Criteria:

Women of childbearing potential not using the contraception method(s) specified during this study. Women of childbearing potential must use proven birth control methods (such as - abstinence, birth control pills, intrauterine device, barrier method combined with gel or foam with spermicide, tubal ligation, or a partner who has had a vasectomy).
Women who are pregnant or breastfeeding.
Patients under the age of 18.
Patients unable to give informed consent.
Known sensitivity to study drug(s) or class of study drug(s).
Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study.
Any cancer other than non-melanoma skin cancer in the past 5 years.
All non-melanoma skin cancers must have been adequately treated at entrance to the study.
Use of any other investigational agent in the last 30 days.
Treatment with prednisone in the past 2 weeks.
Weight or serum IgE levels that place the patient outside standard dosing guidelines for Xolair.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00472030

Contacts

Contact: Debra S Brandt, BSN	319-353-6439	debra-brandt@uiowa.edu
Contact: Janet A Fairley, MD	319-356-3609	janet-fairley@uiowa.edu

Locations

United States, Iowa
University of Iowa, Department of Dermatology	Recruiting
Iowa City, Iowa, United States, 52242
Contact: Debra S Brandt, BSN 319-353-6439 debra-brandt@uiowa.edu
Contact: Janet A Fairley, MD 319-356-3609 janet-fairley@uiowa.edu
Principal Investigator: Janet A Fairley, MD

Sponsors and Collaborators

University of Iowa

Genentech

Investigators

Principal Investigator:

Janet A Fairley, MD

University of Iowa

More Information

Publications:

Dimson OG, Giudice GJ, Fu CL, Van den Bergh F, Warren SJ, Janson MM, Fairley JA. Identification of a potential effector function for IgE autoantibodies in the organ-specific autoimmune disease bullous pemphigoid. J Invest Dermatol. 2003 May;120(5):784-8.

Fairley JA, Fu CL, Giudice GJ. Mapping the binding sites of anti-BP180 immunoglobulin E autoantibodies in bullous pemphigoid. J Invest Dermatol. 2005 Sep;125(3):467-72.

Holgate ST, Djukanovic R, Casale T, Bousquet J. Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy. Clin Exp Allergy. 2005 Apr;35(4):408-16. Review.

Responsible Party:	University of Iowa ( Janet A. Fairley, M.D. )
Study ID Numbers:	100569
Study First Received:	May 8, 2007
Last Updated:	February 13, 2009
ClinicalTrials.gov Identifier:	NCT00472030 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Iowa:

bullous pemphigoid
omalizumab
xolair

IgE
autoimmunity
skin disease

Study placed in the following topic categories:

Anti-Inflammatory Agents
Prednisone
Autoimmune Diseases
Skin Diseases
Skin Diseases, Vesiculobullous
Antineoplastic Agents, Hormonal
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

Anti-Asthmatic Agents
Anti-Allergic Agents
Glucocorticoids
Hormones
Pemphigoid, Bullous
Bullous Pemphigoid
Omalizumab

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Respiratory System Agents
Prednisone
Autoimmune Diseases
Skin Diseases, Vesiculobullous
Skin Diseases
Immune System Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs

Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Asthmatic Agents
Anti-Allergic Agents
Glucocorticoids
Hormones
Pharmacologic Actions
Pemphigoid, Bullous
Therapeutic Uses
Omalizumab

ClinicalTrials.gov processed this record on May 06, 2009