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

An International, Multicenter, Randomized, Double-Blind, Parallel-Group Phase 2 Study Evaluating the Safety and Efficacy of Diacerein 1% Ointment Topical Formulation in Subjects With Epidermolysis Bullosa Simplex

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.

Study Overview

• Status: Terminated
• Conditions: Epidermolysis Bullosa Simplex
• Intervention / Treatment: Drug: diacerein 1% ointment; Drug: A placebo ointment

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Premier Specialists Pty Ltd; The Church
• Austria
  • Salzburg, Austria, A-5020
    • EB House Austria
• France
  • Nice, France, 06202
    • CHU de NICE - Hopital de l'Archet II - Service de Dermatologie
  • Cedex
    • Paris, Cedex, France, 75010
      • Hôpital Saint Louis
    • Paris, Cedex, France, 75015
      • Hôpital Necker-Enfants Malades
• Germany
  • Freiburg, Germany, 79104
    • University Medical Center Freiburg
• Israel
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Netherlands
  • Groningen, Netherlands, AB20;30,001
    • University Medical Center Groningen
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • St. Thomas' Hospital - St Johns Institute of Dermatology
  • England
    • London, England, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Healthcare
  • New York
    • Stony Brook, New York, United States, 11790
      • Stony Brook University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • University of North Carolina - Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425-5780
      • Medical University of South Carolina (MUSC)
  • Texas
    • San Antonio, Texas, United States, 78218
      • Children's Hospital of San Antonio ; Texas Dermatology and Laser Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: diacerein 1% ointment; diacerein 1% ointment will be used for 8 weeks	Drug: diacerein 1% ointment; diacerein 1% ointment administered topically; Other Names: CCP-020
Placebo Comparator: vehicle ointment; vehicle ointment will be used for 8 weeks	Drug: A placebo ointment; vehicle ointment administered topically

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Achieved ≥ 60% Reduction in Body Surface Area (BSA) of EBS Lesions Within Assessment Area	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	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects Who Achieved Success on the Investigator's Global Assessment (IGA)	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	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Castle Creek Pharmaceuticals, LLC
• Investigators: Study Director: Mary Spellman, MD, Castle Creek Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): October 15, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: May 10, 2017
• First Submitted That Met QC Criteria: May 12, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Actual): November 5, 2019
• Last Update Submitted That Met QC Criteria: October 16, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: EBS; bullosa; Epidermolysis; simplex
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases, Vesiculobullous; Skin Abnormalities; Epidermolysis Bullosa; Epidermolysis Bullosa Simplex; Anti-Inflammatory Agents; Diacetylrhein
• Other Study ID Numbers: CCP-020-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No