Anti-IL-5 Therapy in Bullous Pemphigoid(BP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Hospital Inselspital, Berne
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT01705795
First received: October 5, 2012
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Pemphigoid, Bullous
Drug: Mepolizumab (a-IL-5 antibody)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:
  • Time period (in days) from start of therapy until relapse, mepolizumab vs placebo [ Time Frame: Before, at 3-9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes of BP severity score over time (ABSIS) [ Time Frame: At baseline, during therapy, follow up ] [ Designated as safety issue: No ]
  • Changes of pruritus score (visual analog scale) [ Time Frame: At baseline, during therapy, follow up ] [ Designated as safety issue: Yes ]
  • Changes of BP-antibody titers over time [ Time Frame: At baseline, during therapy, follow up ] [ Designated as safety issue: No ]
  • Number of patients with AE, severity of AE [ Time Frame: At baseline, during therapy, follow up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: February 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
mepolizumab 750 mg four times one month apart.
Drug: Mepolizumab (a-IL-5 antibody)
750mg mepolizumab four times over four months
Placebo Comparator: 2
Placebo (saline) four times one month apart
Drug: Placebo
Nacl four times over four months

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01705795

Contacts
Contact: Dagmar Simon, MD +41 31 632 22 78 dagmar.simon@insel.ch

Locations
Switzerland
Dep. of Dermatology, Bern University Hospital Recruiting
Bern, Switzerland, 3010
Contact: Dagmar Simon, MD    +41 31 632 22 78    dagmar.simon@insel.ch   
Principal Investigator: Dagmar Simon         
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
Principal Investigator: Dagmar Simon Inselspital, Bern University Hospital
  More Information

No publications provided

Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT01705795     History of Changes
Other Study ID Numbers: 191/11
Study First Received: October 5, 2012
Last Updated: May 12, 2014
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Pemphigoid, Bullous
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2014