Effect of simvastatin in combination with a superpotent topical corticosteroid in bullous pemphigoid

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2011-004361-32-DE
• Date of registration: 22/05/2012
• Prospective Registration: Yes
• Primary sponsor: Philipps-Universität Marburg
• Public title: Effect of simvastatin in combination with a superpotent topical corticosteroid in bullous pemphigoid
• Scientific title: Effect of simvastatin in combination with a superpotent topical corticosteroid in bullous pemphigoid A prospective multi-centre randomised double-blind placebo-controlled pilot study - SICOPEM
• Date of first enrolment: 26/02/2013
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004361-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Germany

Contacts

• Name: Koordinierungszentrum für Klinische
• Affiliation: Philipps-Universität Marburg

• Name: Koordinierungszentrum für Klinische
• Affiliation: Philipps-Universität Marburg

Key inclusion & exclusion criteria

Inclusion criteria:
• Patients with newly diagnosed or relapsing bullous or pruriginous pemphigoid:
The diagnosis is based on clinical symptoms typical for active bullous or pruriginous pemphigoid: blisters, urticarial plaques, pruriginous papules or eczematous skin alterations.
The clinical extent of BP at screening must exceed values for BPDAI of = 15 (15 or more of max. 240 without damage) or modified ABSIS of = 5 (5 or more of max. 150).
Newly diagnosed patients only:
positive direct immunofluorescence (DIF) with linear deposition of IgG and/or C3 at the dermo-epidermal basal membrane zone
All patients:
1. optional: skin biopsy (histological evidence for subepidermal blister formation)
2. IgG reactivity with blister roof of saline-split human skin using indirect immunofluorescence and IgG reactivity against BP180 and/or BP230 by ELISA
• Male and female patients aged =55 years
• Only confirmed postmenopausal female patients, whose last menorrhoea occurred more than 1 year ago.
• Patients with newly diagnosed or relapsing bullous or pruriginous pemphigoid
The diagnosis is based on clinical symptoms typical for active bullous or pruriginous pemphigoid.
• Age = 55 years
• Written informed consent by patient or written informed consent of the patient’s legal representative
• Karnofsky-Index = 30%


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Predominant or exclusive mucosal involvement
• Treatment with systemic corticosteroids >10mg prednisolone equivalent if systemic corticosteroids cannot be completely tapered until study visit 1
• Treatment with systemic corticosteroids = 10mg prednisolone equivalent for a time period less than four weeks prior to randomisation
• Hypersensitivity to Simvastatin or other ingredients of the IMPs
• Treatment with topical calcineurin inhibitors, dapsone, immunosuppressive drugs (azathioprine, mycofenolate mofetil, cyclophosphamide, methotrexate, ciclosporin) or tetracyclines within the past month prior to randomisation
• Treatment with intravenous immunoglobulins, immunoadsorption or TNF-alpha antagonists within the past 3 months prior to randomisation
• Treatment with rituximab or leflunomide within the past 12 months prior to randomisation
• Concurrent treatment with potent CYP3A4-inhibitors (itraconazole, ketoconazole, fluconazole, posaconazole, HIV protease inhibitors (e.g. nelfinavir), erythromycin, clarithromycin, telithromycin, nefazodon)
• Concurrent treatment with less potent CYP3A4-inhibitors (verapamil, diltiazem, voriconazol, danazol, fibrates, niacin, amiodarone, gemfibrozil, fusidic acid, consumption of grapefruit juice)
• Treatment with simvastatin or other statins four weeks prior to randomisation
• Chronic muscle diseases or increase of creatine kinase above 2.5fold of normal value
• Hereditary muscle diseases in medical history
• Contact hypersensitivity to clobetasol
• Renal dysfunction (creatinine clearance<30ml/min according to the Cockcroft and Gault Formula (30))
• Untreated hypothyreosis
• Active liver disease or prolonged increased transaminase levels >3x upper limit of normal and increased total bilirubin>3mg/dl
• Alcohol dependency
• poorly controlled diabetes mellitus (glycohaemoglobin > 8,0 %)
• Inability to apply topical glucocorticoids and to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
• Illiteracy or insufficient language skills (German) to complete the questionnaires
• Simultaneous participation in another clinical trial except if that other trial does not affect the study as approved and documented by the principal investigators



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Bullous pemphigoid (BP) is the most frequent blistering autoimmune disease of the skin. The disease itself is characterized by the development of bullous lesions, frequently following a prodromal phase with severe itching. Between 10 to 30 percent of patients exhibit mucosal membrane involvement in addition to the skin lesions.

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Trade Name: Simvastatin-ratiopharm®
Product Name: Simvastatin-ratiopharm
Pharmaceutical Form: Capsule
CAS Number: 79902-63-9
Other descriptive name: SIMVASTATIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Secondary endpoints see below

Main Objective: The aim of the pilot study is to gather data about recruitment potential, compliance to the interventional treatment, and adherence to planned study visits in order to decide about the feasibility of a phase III trial that will investigate, whether the relapse-free interval of patients suffering from bullous pemphigoid and treated with high-potent topical corticosteroids can be prolonged by additional oral application of simvastatin 40 mg daily.

Timepoint(s) of evaluation of this end point: Visit 1 (day 0), Visit 2 (day 10), Visit 3 (day 30), Visit 4 (day 90), Visit 5 (day 120), Visit 6 (day 180), Visit 7 (day 270), Visit 8 (day 360)

Primary end point(s): Feasibility criteria:
• Yearly accrual rate
• Proportion of patients compliant with interventional treatment
• Proportion of patients adhering to planned study visits

Secondary Outcome(s)

Secondary end point(s): • Relapse-free survival (RFS) defined as the time interval from randomisation to relapse or death of the patient (This is the designated primary efficacy endpoint of the phase III trial).
• Time to control of disease activity (defined as the time interval from randomisation to the time at which new lesions cease to form and established lesions begin to heal or pruritic symptoms start to abate)
• Time to complete remission on minimal therapy (defined as the absence of new or established lesions or pruritus while patient is receiving minimal therapy for at least 2 months)
• Duration of complete remission on minimal therapy (defined as the time interval from complete remission on minimal therapy to relapse)
Clinical endpoints:
• Cumulative dose of clobetasol cream
• Change in clinical severity scores (modified ABSIS – Autoimmune bullous skin disorder intensity score, BPDAI – Bullous Pemphigoid Disease Activity Index)
• Change in life quality questionnaires (EQ-5D, DLQI, GDS)
• Serum concentration of autoantibodies during follow-up
• Serum concentration of pro- and anti-inflammatory cytokines and other parameters during follow-up

Timepoint(s) of evaluation of this end point: Visit 1 (day 0), Visit 2 (day 10), Visit 3 (day 30), Visit 4 (day 90), Visit 5 (day 120), Visit 6 (day 180), Visit 7 (day 270), Visit 8 (day 360)

Secondary ID(s)

KKS-166

Source(s) of Monetary Support

Universitätsklinikum Marburg-Klinik für Dermatologie

Universitätsklinikum Würzburg-Klinik für Dermatologie