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Safety and Efficacy of Diacerein 1% Ointment for Subjects With Epidermolysis Bullosa Simplex (EBS)

Phase 2
Terminated
Conditions
Epidermolysis Bullosa Simplex
Interventions
Drug: A placebo ointment
Registration Number
NCT03154333
Lead Sponsor
Castle Creek Pharmaceuticals, LLC
Brief Summary

Epidermolysis bullosa simplex (EBS) is a rare genetic skin disease characterized by fragility of the skin and mucous membranes resulting in painful blisters and erosions after minor trauma. The purpose of this study is to compare the efficacy of diacerein 1% ointment to vehicle ointment when applied once-daily for 8 weeks in subjects with EBS.

Detailed Description

The study is an international, multicenter, randomized, double-blind, vehicle-controlled, parallel group study to evaluate the safety and efficacy of diacerein 1% ointment for the treatment of subjects with EBS. Participants were assigned to study groups receiving either diacerein 1% ointment or vehicle ointment for 8 weeks, followed by an 8 week follow-up period. Approximately 80 subjects were to be randomized to one of the 2 treatment groups.

The primary objective of this study is to compare the efficacy of diacerein 1% ointment to vehicle ointment based on reduction in body surface area (BSA) of EBS lesions being treated when applied once-daily for 8 weeks in subjects with EBS. The secondary objectives are to compare the effects of diacerein 1% ointment to vehicle ointment in subjects with EBS in changes in Investigator Global Assessment (IGA) scores, pain, pruritus, mobility, and safety and tolerability.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
54
Inclusion Criteria
  • Subject is at least 4 years of age at Screening

  • Subject has a documented genetic mutation consistent with EBS. Gene mutations acceptable for inclusion are as follows: KRT5, KRT14, PLEC1, TGM5, PKP1, DSP, FERMT1, EXPH5, DST, KLHL24.

  • Subject has an Assessment Area of EBS lesions to be treated, that is ≥2% body surface area (BSA) and the EBS lesions are in one or both of the following body areas:

    • Localized: plantar and/or palmar areas
    • Generalized: arms, legs, torso, hands and feet
  • Subject's EBS lesions in the Assessment Area have an Investigator's Global Assessment (IGA) score of ≥3

  • Subject/caregiver agrees to not use any topical therapies other than the study medication that might influence the status of the EBS lesions during the duration of the study

  • Subject is non-pregnant as confirmed by a negative urine pregnancy screen, non-lactating and is not planning for pregnancy during the study period

  • If the subject is a woman of childbearing potential, agrees to use an approved effective method of birth control

  • Subject is in good general health and free of any known disease state or physical condition which might impair evaluation of the EBS lesions or which exposes the subject to an unacceptable risk by study participation

Key

Exclusion Criteria
  • Subject has EBS lesions to be treated that are infected
  • Subject has used any diacerein containing product within 6 months prior to Screening
  • Subject has used systemic immunotherapy or cytotoxic chemotherapy within 60 days prior to Screening
  • Subject has used systemic steroidal therapy or has used topical steroidal therapy on the EBS lesions to be treated within 30 days prior to Baseline
  • Subject has evidence of a systemic infection or has used systemic antibiotics within 7 days prior to Screening
  • Subject is currently using systemic analgesics and/or anti-histamine therapy, for treatment of EBS lesions unless on a stable regimen (i.e., the same dosing regimen) for at least 4 weeks prior to Screening
  • Subject has used any systemic diuretics or cardiac glycosides or any systemic product that might put the subject at undue risk
  • Subject has used any topical product containing allantoin on the EBS lesions to be treated within 30 days prior to Screening
  • Subject has a current malignancy, or a history of treatment for a malignancy within 2 years prior to Screening
  • Subject currently has diabetes mellitus (HbA1c ≥6.5%) or controlled diabetes (HbA1c < 6.5%)
  • Subject has a history of cardiac, hepatic (ALT and or AST >2x ULN, Total bilirubin >1.5x ULN at Screening), or renal disease (eGFR<30 ml/min/1.73 m^2)
  • Subject has a non-EBS skin disease or condition (e.g., sunburn) that might put the subject at undue risk by study participation or interferes with the study medication application or the study assessments

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
diacerein 1% ointmentdiacerein 1% ointmentdiacerein 1% ointment will be used for 8 weeks
vehicle ointmentA placebo ointmentvehicle ointment will be used for 8 weeks
Primary Outcome Measures
NameTimeMethod
Proportion of Subjects Who Achieved ≥ 60% Reduction in Body Surface Area (BSA) of EBS Lesions Within Assessment AreaBaseline to Week 8

Analysis of the proportion of subjects who achieved a ≥60% reduction in Body Surface Area (BSA) of EBS lesions within Assessment Area from Baseline to Week 8

Secondary Outcome Measures
NameTimeMethod
The Proportion of Subjects Who Achieved Success on the Investigator's Global Assessment (IGA)Baseline to Week 8

The investigator's global assessment (IGA) is a five-point scale that is used for overall clinical assessment of severity of disease and classifies EBS-involved skin with a score ranging from 0-4. Success on the IGA was defined as ≥2-point reduction from Baseline to Visit 6 (Week 8).

IGA Scoring:

0 = Clear; 1 = Near Clear; 2 = Mild; 3 = Moderate; 4 = Severe

Minimum score = 0 Maximum score = 4; higher score = worse outcome

Trial Locations

Locations (22)

University of Missouri Healthcare

🇺🇸

Columbia, Missouri, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Children's Hospital of San Antonio ; Texas Dermatology and Laser Specialists

🇺🇸

San Antonio, Texas, United States

University Medical Center Freiburg

🇩🇪

Freiburg, Germany

St. Thomas' Hospital - St Johns Institute of Dermatology

🇬🇧

London, United Kingdom

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Hopital Necker-Enfants Malades

🇫🇷

Paris, Cedex, France

CHU de NICE - Hopital de l'Archet II - Service de Dermatologie

🇫🇷

Nice, France

Northwestern University

🇺🇸

Chicago, Illinois, United States

Stony Brook University Medical Center

🇺🇸

Stony Brook, New York, United States

Great Ormond Street Hospital

🇬🇧

London, England, United Kingdom

Phoenix Childrens Hospital

🇺🇸

Phoenix, Arizona, United States

Stanford University

🇺🇸

Palo Alto, California, United States

EB House Austria

🇦🇹

Salzburg, Austria

Ann and Robert H. Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

University Medical Center Groningen

🇳🇱

Groningen, Netherlands

University of North Carolina - Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Medical University of South Carolina (MUSC)

🇺🇸

Charleston, South Carolina, United States

Premier Specialists Pty Ltd; The Church

🇦🇺

Kogarah, New South Wales, Australia

Hopital Saint Louis

🇫🇷

Paris, Cedex, France

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