Clinical trial NCT00472030: Efficacy and Safety of Omalizumab in Bullous Pemphigoid
Official title: An Open Label Case Series on the Effects of Xolair (Omalizumab) in Bullous Pemphigoid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bullous Pemphigoid
Keywords: bullous pemphigoid
omalizumab
xolair
IgE
autoimmunity
skin disease
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2007-05-10
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Median Time From First Dose of Omalizumab Treatment to Cessation of New Blisters.
timeFrame: Up to 24 weeks
measure: Percent Decrease in the Total Body Surface Area Affected By Active Bullous Pemphigoid Skin Disease From Day 0 to Week 24.
timeFrame: Up to 24 weeks
measure: Median Increase in Prednisone Dosage Measured at Week 4, 8 and 24 in Patients Treated With Omalizumab and in Patients Receiving Standard Therapy.
timeFrame: Week 4, Week 8 and Week 24
Secondary outcomes:
measure: Decrease in Anti-BP180 IgG (Immunoglobulin G Anti-Bullous Pemphigoid 180 Antibody) Following Treatment With Omalizumab.
timeFrame: Up to 24 weeks
measure: Decrease in Eosinophil Levels Following Treatment With Omalizumab.
timeFrame: Baseline, 24 weeks.
measure: Decrease in Anti-BP230 Antibody IgG (Anti-bullous Pemphigoid 230 Antibody Immunoglobulin G) At Baseline and Week 16
timeFrame: Up to 24 weeks
measure: Change in Histamine Release Assay Following Treatment With Omalizumab.
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa, Department of Dermatology
state: Iowa
Study officials:
affiliation: University of Iowa
name: Janet A Fairley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.