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Efficacy and Safety of Omalizumab in Bullous Pemphigoid

Primary Purpose

Bullous Pemphigoid

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Omalizumab

prednisone

About this trial

This is an interventional treatment trial for Bullous Pemphigoid focused on measuring bullous pemphigoid, omalizumab, xolair, IgE, autoimmunity, skin disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Iowa, Department of Dermatology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Omalizumab

Prednisone

Arm Description

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.

The control arm of the study will receive standard prednisone therapy to a maximum dose of 0.5 mg/kg/day.

Outcomes

Primary Outcome Measures

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.

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).

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.

Secondary Outcome Measures

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

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

Decrease in Anti-BP230 Antibody IgG (Anti-bullous Pemphigoid 230 Antibody Immunoglobulin G) At Baseline and Week 16

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.

Full Information

NCT ID

NCT00472030

First Posted

May 8, 2007

Last Updated

September 17, 2012

Sponsor

University of Iowa

Collaborators

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00472030

Brief Title

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

2. Study Status

Record Verification Date

September 2012

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Iowa

Collaborators

Genentech, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bullous Pemphigoid

Keywords

bullous pemphigoid, omalizumab, xolair, IgE, autoimmunity, skin disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Omalizumab

Arm Type

Experimental

Arm Description

Arm Title

Prednisone

Arm Type

Active Comparator

Arm Description

The control arm of the study will receive standard prednisone therapy to a maximum dose of 0.5 mg/kg/day.

Intervention Type

Drug

Intervention Name(s)

Omalizumab

Other Intervention Name(s)

Xolair

Intervention Description

Intervention Type

Drug

Intervention Name(s)

prednisone

Intervention Description

Prednisone, to a maximum dose of 0.5 mg/kg/day.

Primary Outcome Measure Information:

Title

Median Time From First Dose of Omalizumab Treatment to Cessation of New Blisters.

Description

The study subject underwent physical examination and was assessed for cessation of new blister formation via physical examination and photography.

Time Frame

Up to 24 weeks

Title

Percent Decrease in the Total Body Surface Area Affected By Active Bullous Pemphigoid Skin Disease From Day 0 to Week 24.

Description

Time Frame

Up to 24 weeks

Title

Median Increase in Prednisone Dosage Measured at Week 4, 8 and 24 in Patients Treated With Omalizumab and in Patients Receiving Standard Therapy.

Description

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.

Time Frame

Week 4, Week 8 and Week 24

Secondary Outcome Measure Information:

Title

Decrease in Anti-BP180 IgG (Immunoglobulin G Anti-Bullous Pemphigoid 180 Antibody) Following Treatment With Omalizumab.

Description

Anti-BP180 IgG levels were completed using an Elisa assay. Anti-BP180 IgG levels were obtained prior to baseline and at week 16

Time Frame

Up to 24 weeks

Title

Decrease in Eosinophil Levels Following Treatment With Omalizumab.

Description

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

Time Frame

Baseline, 24 weeks.

Title

Decrease in Anti-BP230 Antibody IgG (Anti-bullous Pemphigoid 230 Antibody Immunoglobulin G) At Baseline and Week 16

Time Frame

Up to 24 weeks

Title

Change in Histamine Release Assay Following Treatment With Omalizumab.

Description

The histamine release assay measures the release of histamine which occurs upon stimulation of basophilic granulocytes depending upon their sensitivity to an allergen.

Time Frame

Up to 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janet A Fairley, MD

Organizational Affiliation

University of Iowa

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Iowa, Department of Dermatology

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

12713582

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.

Results Reference

background

PubMed Identifier

16117787

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.

Results Reference

background

PubMed Identifier

15836747

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.

Results Reference

background

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Efficacy and Safety of Omalizumab in Bullous Pemphigoid

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