Efficacy and Safety of Fumaric Acid Esters (Fumaderm®) in the Treatment of Patients With Cutaneous Lupus Erythematosus (FumaCLE)

Efficacy and Safety of Fumaric Acid Esters (Fumaderm®) in the Treatment of Patients With Cutaneous Lupus Erythematosus: A Mono-Centre, Open-Label, Prospective Pilot Study

The purpose of this study is to evaluate the therapeutic effect of fumaric acid esters (Fumaderm®) in the treatment of Cutaneous Lupus Erythematosus with respect to proportion of responders based on the Revised Cutaneous Lupus Disease Area and Severity Index (RCLASI) activity score for skin lesions at baseline and after 24 weeks of treatment or at the latest assessment for patients who withdrew prematurely (Last Observation Carried Forward, LOCF).

Study Overview

• Status: Completed
• Conditions: Lupus Erythematosus, Cutaneous
• Intervention / Treatment: Drug: Fumaric acid esters

Detailed Description

At screening, patients meeting the inclusion and exclusion criteria will be asked to provide written informed consent. Male patients and female patients without childbearing potential will also complete other screening procedures including vital signs, physical examination, and patients and physicians efficacy assessments.

Treatment will be started as soon as possible after screening and not later than 1 month after screening.

The patients will receive a treatment either with Fumaderm® initial and/or Fumaderm® enteric-coated tablets. Fumaderm® initial will be usually administered during the first three weeks of treatment and / or during the trial when adaptation of the daily dosage will be required due to the occurrence of adverse reactions, e.g gastrointestinal.

Throughout the trial, daily use of sunscreens (sun protection factor, SPF≥50) will be recommended to all patients. The management of CLE may also involve the use of topical medications, such as topical steroids, or systemic rescue medications, such as antimalarials.

All patients will be evaluated with the RCLASI, PAGI and VAS after 12 weeks and at the end of treatment. Adverse Events (AE) will be recorded at each visit until 4 weeks after the end of therapy. Serious Adverse Events (SAE) must be reported if they occur up to 4 weeks after the end of therapy.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Muenster, Germany, 48149
    • Department of Dermatology, University Hospital Muenster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A clinical and histological diagnosis of CLE (DLE, SCLE, LET, without major systemic involvement) who failed to response to topical corticosteroids;
• Total RCLASI activity score of >6 (at least 3 points in at least 2 locations) on an assessment of erythema, scale/hyperkeratosis, edema/infiltration and subcutaneous nodule/plaque of the lesion (mucous membrane lesions/alopecia excluded);
• Women of childbearing potential must agree to use at least one primary method of contraception and preferably, at the same time, a secondary method of contraception from the time of screening, throughout trial treatment, and for at least one month after finishing treatment.
• Signed informed consent.

Exclusion Criteria:

• Patients unable to comply with the requirements of the study;
• Only scarred cutaneous target lesions without activity;
• Systemic Lupus Erythematosus (SLE) with major systemic organ involvement, e.g. clinical significant renal involvement, requiring systemic medical treatment for the disease;
• Active skin disease other than CLE or another progressive or serious disease that interferes with the study outcome;
• Symptoms of a clinically significant illness that may influence the outcome of the study in the four weeks before and during the study;
• Active severe infection diseases, including chronic or localized;
• Known malignancies in the last 5 years, other than effective treated non melanoma skin cancer;
• Severe liver- or kidney- disease;
• Severe gastrointestinal disease, like gastric or duodenal ulcer;
• Severe hematologic disorders;
• Patients with leucopenia (<3.000/mm³);
• Patients with lymphopenia (<500/mm³);
• Patients with known hypersensitivity to fumaric acid esters or their derivatives, or to any study medication components;
• Topical corticosteroids within 14 days prior to dosing;
• Local treatment with fumaric acid derivates;
• Initiation or change in the dose of any current systemic medication for the treatment of CLE/SLE prior to the study (time depending on drug class);
• Treatment with immunosuppressive drugs for other reasons, 4 weeks prior and within the study;
• Concomitant treatment with drugs with a known photosensitizing potential, e.g. tetracyclines, griseofulvin, thiazides, furosemide, sulfonamides or tolbutamide;
• Drugs associated to CLE-induction: terbinafine, hydrochlorothiazide, diltiazem, verapamil, nifedipine, nitrendipine, fluorouracil, penicillamine, infliximab, adalimumab, etanercept, pantoprazole;
• Drugs interfering/ interacting with fumaric acid esters;
• Drugs with nephrotoxic potential, e.g. retinoids, psoralens, methotrexate, cyclosporine, immunosuppressants, cytostatics;
• Participation in another clinical trial including the four week period preceding the study or having received a non-licensed drug within the last 3 months prior to the study;
• Pregnancy (according to pregnancy test) or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fumaric acid esters	Drug: Fumaric acid esters; Starting from 1 tablet Fumaderm® initial per day, with titration up to 6 tablets Fumaderm® per day; in case of side effects, the dose will be adapted to the highest tolerable levels; Other Names: Fumaderm®; Fumaderm® initial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy outcome is the response rate at week 24 or at the latest assessment for patients who withdrew prematurely.	Response is defined as a reduction of 50% in the total RCLASI activity for skin lesions, compared to the baseline value ("RCLASI 50").	Week 24 or at the latest assessment for patients who withdrew prematurely (Last Observation Carried Forward, LOCF).

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with RCLASI 50 at week 12 of treatment	Week 12 of treatment
Proportion of patients with at least partial response at end of therapy (with regard to RCLASI activity score for skin lesions)	End of therapy (up to 24 weeks)
Time from start of treatment to first RCLASI 50 assessment (time to response).	Time to response (up to 24 weeks)
Patient's global assessment and VAS for itch and pain 12 weeks after the beginning of treatment and at the end of therapy.	12 weeks after the beginning of treatment and at the end of therapy (up to 24 weeks).
Number of Participants with Adverse Events (AEs) and their severity.	24 weeks of treatment + 4 weeks of follow up

Collaborators and Investigators

• Sponsor: University Hospital Muenster
• Investigators: Principal Investigator: Annegret Kuhn, Prof. Dr., Department of Dermatology, University Hospital Muenster

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: April 29, 2011
• First Submitted That Met QC Criteria: May 11, 2011
• First Posted (Estimate): May 12, 2011

Study Record Updates

• Last Update Posted (Estimate): February 28, 2014
• Last Update Submitted That Met QC Criteria: February 27, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: C17.300.475; C17.800.480
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: UKM 10_0020