Bullous Pemphigoid
Conditions
Keywords
bullous pemphigoid, omalizumab, xolair, IgE, autoimmunity, skin disease
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.
Interventions
DRUGOmalizumab
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.
DRUGprednisone
Prednisone, to a maximum dose of 0.5 mg/kg/day.
Sponsors
Genentech, Inc.
University of Iowa
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time From First Dose of Omalizumab Treatment to Cessation of New Blisters. | Up to 24 weeks | 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. | Up to 24 weeks | 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. | Week 4, Week 8 and Week 24 | 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
| Measure | Time frame | Description |
|---|---|---|
| Decrease in Anti-BP180 IgG (Immunoglobulin G Anti-Bullous Pemphigoid 180 Antibody) Following Treatment With Omalizumab. | Up to 24 weeks | Anti-BP180 IgG levels were completed using an Elisa assay. Anti-BP180 IgG levels were obtained prior to baseline and at week 16 |
| Change in Histamine Release Assay Following Treatment With Omalizumab. | Up to 24 weeks | The histamine release assay measures the release of histamine which occurs upon stimulation of basophilic granulocytes depending upon their sensitivity to an allergen. |
| Decrease in Eosinophil Levels Following Treatment With Omalizumab. | Baseline, 24 weeks. | 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 | Up to 24 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab Treatment Arm Patients with bullous pemphigoid will be treated with omalizumab for a total treatment period of 16 weeks. | 2 |
| Prednisone Standard Therapy Treatment Arm The control arm of the study will receive standard prednisone therapy to a maximum dose of 0.5 mg/kg/day. | 0 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Omalizumab Treatment Arm |
|---|---|---|
| Age Categorical <=18 years | 0 participants | 0 participants |
| Age Categorical >=65 years | 2 participants | 2 participants |
| Age Categorical Between 18 and 65 years | 0 participants | 0 participants |
| Age Continuous | 78 years STANDARD_DEVIATION 0 | 78 years STANDARD_DEVIATION 0 |
| Gender Female | 2 participants | 2 participants |
| Gender Male | 0 participants | 0 participants |
| Region of Enrollment United States | 2 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 2 | 0 / 0 |
| serious Total, serious adverse events | 1 / 2 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Week 4, Week 8 and Week 24
Population: Neither subject required treatment with Prednisone. Since we did not enroll any subject in the Prednisone Standard Therapy Treatment Arm we do not have any measurements for this outcome
Primary
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.
Time frame: Up to 24 weeks
Population: The population analyzed included one subject who received Omalizumab treatment on Day 1, Week 2,4,6,8,10,12 and 14 and completed assessments through week 24. A second subject enrolled in the study and received one treatment with Omalizumab and was terminated from the study per investigator at Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab Treatment Arm | Median Time From First Dose of Omalizumab Treatment to Cessation of New Blisters. | 6 weeks |
Primary
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).
Time frame: Up to 24 weeks
Population: The population analyzed included one subject who received Omalizumab treatment on Day 1, Week 2,4,6,8,10,12 and 14 and completed assessments through week 24. A second subject enrolled in the study and received one treatment with Omalizumab and was terminated from the study per investigator at Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab Treatment Arm | Percent Decrease in the Total Body Surface Area Affected By Active Bullous Pemphigoid Skin Disease From Day 0 to Week 24. | 22.5 percentage of active skin disease |
Secondary
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.
Time frame: Up to 24 weeks
Population: We were unable to complete this assay in our research subjects due to technical difficulties.
Secondary
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
Time frame: Up to 24 weeks
Population: The population analyzed included one subject who received Omalizumab treatment on Day 1, Week 2,4,6,8,10,12 and 14 and completed assessments through week 24. A second subject enrolled in the study and received one treatment with Omalizumab and was terminated from the study per investigator at Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab Treatment Arm | Decrease in Anti-BP180 IgG (Immunoglobulin G Anti-Bullous Pemphigoid 180 Antibody) Following Treatment With Omalizumab. | 92.06 units per milliliter |
Secondary
Decrease in Anti-BP230 Antibody IgG (Anti-bullous Pemphigoid 230 Antibody Immunoglobulin G) At Baseline and Week 16
Time frame: Up to 24 weeks
Population: The population analyzed included one subject who received Omalizumab treatment on Day 1, Week 2,4,6,8,10,12 and 14 and completed assessments through week 24. A second subject enrolled in the study and received one treatment with Omalizumab and was terminated from the study per investigator at Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab Treatment Arm | Decrease in Anti-BP230 Antibody IgG (Anti-bullous Pemphigoid 230 Antibody Immunoglobulin G) At Baseline and Week 16 | 62.6 units per milliliter |
Secondary
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
Time frame: Baseline, 24 weeks.
Population: The population analyzed included one subject who received Omalizumab treatment on Day 1, Week 2,4,6,8,10,12 and 14 and completed assessments through week 24. A second subject enrolled in the study and received one treatment with Omalizumab and was terminated from the study per investigator at Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab Treatment Arm | Decrease in Eosinophil Levels Following Treatment With Omalizumab. | 2.16 cells/microliter |