Efficacy and Safety of Omalizumab in Bullous Pemphigoid

An Open Label Case Series on the Effects of Xolair (Omalizumab) in Bullous Pemphigoid

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.

Study Overview

• Status: Completed
• Conditions: Bullous Pemphigoid
• Intervention / Treatment: Drug: Omalizumab; Drug: prednisone

Detailed Description

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

Study Rationale: The current treatment for bullous pemphigoid is non-specific immunosuppression, causing great morbidity in these patients. Recently, pathogenic Immunoglogulin Class E 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 Omalizumab (Xolair) will be compared to patients receiving standard treatment with prednisone.

Number of centers and 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 less than 18 years of age, and patients unable to give consent will be excluded from this preliminary study.

Investigational drug: Xolair® (Omalizumab)

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

Evaluation criteria: Primary: 1. Time to cessation of new blister formation. 2. Percent body surface area of skin 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. Number of circulating eosinophils 2. Measurement of circulating anti-BMZ (basement membrane zone) autoantibodies 3. Histamine release assay.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa, Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omalizumab; Patients will be treated with 150-375 milligrams of Omalizumab (Xolair), based on their baseline weight and serum Immunoglobulin E levels. Omalizumab will be administered subcutaneously on Day 1, and on Week 2, 4, 6, 8, 10, 12 and 14 treatment.	Drug: Omalizumab; Patients will be treated with 150-375 milligrams of Omalizumab (Xolair), based on their baseline weight and serum Immunoglobulin E levels. Omalizumab will be administered subcutaneously on Day 1, and on Week 2, 4, 6, 8, 10, 12 and 14 treatment.; Other Names: Xolair
Active Comparator: Prednisone; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time From First Dose of Omalizumab Treatment to Cessation of New Blisters.	The study subject underwent physical examination and was assessed for cessation of new blister formation via physical examination and photography.	Up to 24 weeks
Percent Decrease in the Total Body Surface Area Affected By Active Bullous Pemphigoid Skin Disease From Day 0 to Week 24.	Measurement of total body surface area affected by bullous pemphigoid active skin disease(active erosions, blisters, and/or lesions) was measured at Day 0 (prior to treatment with Omalizumab) and at 24 weeks (24 weeks is end of study).	Up to 24 weeks
Median Increase in Prednisone Dosage Measured at Week 4, 8 and 24 in Patients Treated With Omalizumab and in Patients Receiving Standard Therapy.	The total dose of prednisone required to control the bullous pemphigoid at week 4, 8 and 24 weeks was to be calculated in both arms of this study.	Week 4, Week 8 and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in Anti-BP180 IgG (Immunoglobulin G Anti-Bullous Pemphigoid 180 Antibody) Following Treatment With Omalizumab.	Anti-BP180 IgG levels were completed using an Elisa assay. Anti-BP180 IgG levels were obtained prior to baseline and at week 16	Up to 24 weeks
Decrease in Eosinophil Levels Following Treatment With Omalizumab.	The subject's eosinophil count measured at baseline was compared to the eosinophil count at week 8. A normal eosinophil count at the University of Iowa Hospital lab is 0-0.4 cells per microliter	Baseline, 24 weeks.
Decrease in Anti-BP230 Antibody IgG (Anti-bullous Pemphigoid 230 Antibody Immunoglobulin G) At Baseline and Week 16		Up to 24 weeks
Change in Histamine Release Assay Following Treatment With Omalizumab.	The histamine release assay measures the release of histamine which occurs upon stimulation of basophilic granulocytes depending upon their sensitivity to an allergen.	Up to 24 weeks

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Janet A Fairley, MD, University of Iowa

Publications and helpful links

General 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. doi: 10.1046/j.1523-1747.2003.12146.x.
• 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. doi: 10.1111/j.0022-202X.2005.23853.x.
• 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. doi: 10.1111/j.1365-2222.2005.02191.x.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: May 8, 2007
• First Submitted That Met QC Criteria: May 8, 2007
• First Posted (Estimate): May 10, 2007

Study Record Updates

• Last Update Posted (Estimate): October 16, 2012
• Last Update Submitted That Met QC Criteria: September 17, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: omalizumab; skin disease; autoimmunity; IgE; bullous pemphigoid; xolair
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigoid, Bullous; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Prednisone; Omalizumab
• Other Study ID Numbers: 100569 (Other Identifier: GSK)