Anti-IL-5 Therapy in Bullous Pemphigoid (BP)
Primary Purpose
Pemphigoid, Bullous
Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Mepolizumab (a-IL-5 antibody)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pemphigoid, Bullous
Eligibility Criteria
Inclusion Criteria:
- Men, women >18 years
- Active BP (diagnosed by typical clinical picture and skin biopsy)
- Must give written informed consent
Exclusion Criteria
- Patients with other skin disease
- Patients with severe diseases of other organ systems
- Systemic treatment for BP
- Topical therapy with corticosteroids and other anti-inflammatory substances
- For female patients, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception (defined as methods with <1% failure rate)
- Female patients who are currently pregnant or breast-feeding
- Current abuse of alcohol and/or drugs
- History of or a new diagnosis or treatment of an invasive malignancy within 5 years of enrollment. Patients with a history of treated squamous cell and/or basal cell carcinomas limited to the skin are not excluded.
- History of recurrent clinically significant infection
- Congenital or acquired immunodeficiency syndrome
- Current enrollment in any other investigational drug study
- Previous participation in this study or previous studies with mepolizumab
- Hypersensitivity to mepolizumab or its constituents
Sites / Locations
- Dep. of Dermatology, Bern University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Mepolizumab
Placebo
Arm Description
Mepolizumab 750 mg four times one month apart.
Placebo (saline) four times one month apart
Outcomes
Primary Outcome Measures
Time period (in days) from start of therapy until relapse, mepolizumab vs placebo
Secondary Outcome Measures
Changes of BP severity score over time (ABSIS)
Changes of pruritus score (visual analog scale)
Changes of BP-antibody titers over time
Number of patients with AE, severity of AE
Full Information
NCT ID
NCT01705795
First Posted
October 5, 2012
Last Updated
February 27, 2017
Sponsor
Insel Gruppe AG, University Hospital Bern
1. Study Identification
Unique Protocol Identification Number
NCT01705795
Brief Title
Anti-IL-5 Therapy in Bullous Pemphigoid (BP)
Official Title
Anti-IL-5 Therapy in Bullous Pemphigoid. Randomized, Placebo-controlled, Double-blind Study Evaluating the Effect of Anti-IL-5 Therapy in Patients With Bullous Pemphigoid.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
February 13, 2013 (Actual)
Primary Completion Date
January 31, 2017 (Actual)
Study Completion Date
January 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Randomized, placebo-controlled, double-blind study evaluating the effect of anti-IL-5-therapy in patients with bullous pemphigoid. The primary study objective is to determine the efficacy of an anti-IL-5 monoclonal antibody therapy, administered as 750mg mepolizumab, in patients with bullous pemphigoid.
Detailed Description
Background
Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease. It characteristically affects the elderly (>70 years) with an annual incidence of 5 to 35 per million. This is comparable with the incidence of eosinophilic esophagitis that we determined with approximately 14 per million. Eosinophilic esophagitis has been recognized as an emerging medical problem and, consequently, several studies with anti-IL-5-antibodies have been performed and are still ongoing. It should be noted, however, that, in contrast to eosinophilic esophagitis, the incidence of BP is dramatically increasing with an average of 17% per year. Moreover, with the increase of the proportion of the elderly in the industrialized world, the medical problems associated with BP will even be more visible in the near future. For instance, patients with BP have an increased mortality risk of 2.3. In the US, an increase in mortality of BP patients has been noticed from 1979 to 2002. Taken together, BP is a frequent disease that affects mostly the elderly.
BP often starts with extremely pruritic skin lesions resembling eczema or urticaria before vesicles and blisters arise. In 10-30% of patients, BP also involves the oral mucosa. Disease severity can be determined by means of the autoimmune bullous skin disorder intensity score (ABSIS) that evaluates the involved area as well as the disease activity. The disease is due to an autoimmune response to structural components of junctional adhesion complexes leading to the damage of the dermal-epidermal junction with subepidermal blister formation. Specifically, autoreactive B and T cell responses against the hemidesmosomal antigens BP180 and BP230 have been identified. Serum levels of autoantibodies to BP180 reflect the disease severity and activity. The T cells are memory CD4+ cells producing both Th1 and Th2 cytokines, mostly IL-4, IL-5 and IL-13. IL-5 as well as eotaxin are abundantly found in blister fluids. The production of IL-5 is indeed associated with blood eosinophilia and significant eosinophil infiltration in the skin of BP patients. Eosinophils are thought to be critically implicated in blister formation by releasing toxic granule proteins (ESP, MBP) and proteolytic enzymes.
Systemic corticosteroids have been widely used for the treatment of BP. Nevertheless, the use of steroids is limited by their side effects. in therapy-resistant cases, immunosuppressive drugs such as azathioprine, chlorambucil, cyclophosphamide, cyclosporine, methotrexate, mycophenolate mofetil are employed, but their corticosteroid-sparing effect and overall benefit in BP is highly disputed. 70% of the relapses are usually observed within three months, 85% within 6 months after stopping therapy.
Since eosinophils are characteristically found in the skin at early stages of the disease before blisters occur and contribute to tissue damage, targeting eosinophils by reducing their number and activation might thus be a promising alternative therapeutic approach. Anti-IL-5 antibody therapy has been shown to be effective in depleting eosinophils, e.g. in diseases such as eosinophilic esophagitis and hypereosinophilic syndrome.
Objective
To determine the safety and efficacy of mepolizumab in patients with bullous pemphigoid.
Methods
clinical trial with 750 mg mepolizumab over three months, evaluate time period from start of therapy until relapse, ABSIS-Score, Pruritus Score, Antibody levels, immuno pathological evaluation of skin biopsy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pemphigoid, Bullous
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mepolizumab
Arm Type
Active Comparator
Arm Description
Mepolizumab 750 mg four times one month apart.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (saline) four times one month apart
Intervention Type
Drug
Intervention Name(s)
Mepolizumab (a-IL-5 antibody)
Intervention Description
750mg mepolizumab four times over four months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Nacl four times over four months
Primary Outcome Measure Information:
Title
Time period (in days) from start of therapy until relapse, mepolizumab vs placebo
Time Frame
Before, at 3-9 months
Secondary Outcome Measure Information:
Title
Changes of BP severity score over time (ABSIS)
Time Frame
At baseline, during therapy (expected to be ca. 4 months), follow up (expected to be ca. 9 months)
Title
Changes of pruritus score (visual analog scale)
Time Frame
At baseline, during therapy (expected to be ca. 4 months), follow up (expected to be ca. 9 months)
Title
Changes of BP-antibody titers over time
Time Frame
At baseline, during therapy (expected to be ca. 4 months), follow up (expected to be ca. 9 months)
Title
Number of patients with AE, severity of AE
Time Frame
At baseline, during therapy (expected to be ca. 4 months), follow up (expected to be ca. 9 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men, women >18 years
Active BP (diagnosed by typical clinical picture and skin biopsy)
Must give written informed consent
Exclusion Criteria
Patients with other skin disease
Patients with severe diseases of other organ systems
Systemic treatment for BP
Topical therapy with corticosteroids and other anti-inflammatory substances
For female patients, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception (defined as methods with <1% failure rate)
Female patients who are currently pregnant or breast-feeding
Current abuse of alcohol and/or drugs
History of or a new diagnosis or treatment of an invasive malignancy within 5 years of enrollment. Patients with a history of treated squamous cell and/or basal cell carcinomas limited to the skin are not excluded.
History of recurrent clinically significant infection
Congenital or acquired immunodeficiency syndrome
Current enrollment in any other investigational drug study
Previous participation in this study or previous studies with mepolizumab
Hypersensitivity to mepolizumab or its constituents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dagmar Simon
Organizational Affiliation
Inselspital, Bern University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dep. of Dermatology, Bern University Hospital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
12. IPD Sharing Statement
Learn more about this trial
Anti-IL-5 Therapy in Bullous Pemphigoid (BP)
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