Clinical trial NCT03154333: Safety and Efficacy of Diacerein 1% Ointment for Subjects With Epidermolysis Bullosa Simplex (EBS)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Epidermolysis Bullosa Simplex
Keywords: Epidermolysis
bullosa
simplex
EBS
Lead sponsor: Castle Creek Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2017-05-16
Enrollment: 54
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Subjects Who Achieved ≥ 60% Reduction in Body Surface Area (BSA) of EBS Lesions Within Assessment Area
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: The Proportion of Subjects Who Achieved Success on the Investigator's Global Assessment (IGA)
timeFrame: Baseline to Week 8
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri Healthcare
state: Missouri
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: San Antonio
country: United States
facility: Children's Hospital of San Antonio ; Texas Dermatology and Laser Specialists
state: Texas
city: Kogarah
country: Australia
facility: Premier Specialists Pty Ltd; The Church
state: New South Wales
city: Salzburg
country: Austria
facility: EB House Austria
city: Paris
country: France
facility: Hopital Saint Louis
state: Cedex
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
state: Cedex
city: Nice
country: France
facility: CHU de NICE - Hopital de l'Archet II - Service de Dermatologie
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
state: England
city: London
country: United Kingdom
facility: St. Thomas' Hospital - St Johns Institute of Dermatology
Study officials:
affiliation: Castle Creek Pharmaceuticals
name: Mary Spellman, MD
role: STUDY_DIRECTOR
References: