Epidermolysis Bullosa Simplex
Conditions
Keywords
Epidermolysis, bullosa, simplex, EBS
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.
Interventions
diacerein 1% ointment administered topically
DRUGA placebo ointment
vehicle ointment administered topically
Sponsors
Castle Creek Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Achieved ≥ 60% Reduction in Body Surface Area (BSA) of EBS Lesions Within Assessment Area | Baseline 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Australia, Austria, France, Germany, Israel, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diacerein 1% Ointment diacerein 1% ointment will be used for 8 weeks
diacerein 1% ointment: diacerein 1% ointment administered topically | 28 |
| Vehicle Ointment vehicle ointment will be used for 8 weeks
vehicle ointment administered topically | 26 |
| Total | 54 |
Baseline characteristics
| Characteristic | Diacerein 1% Ointment | Vehicle Ointment | Total |
|---|---|---|---|
| Age, Customized Age <8 years old | 13 Participants | 12 Participants | 25 Participants |
| Age, Customized Age greater than or equal to 8 years old | 15 Participants | 14 Participants | 29 Participants |
| Baseline BSA(Body Surface Area) of EBS(Epidermolysis Bullosa Simplex) Lesions within Assessment Area | 5.76 Percent of BSA STANDARD_DEVIATION 4.674 | 7.13 Percent of BSA STANDARD_DEVIATION 7.606 | 6.42 Percent of BSA STANDARD_DEVIATION 6.237 |
| Baseline IGA Score of 3 or 4 IGA Score: 3 | 26 Participants | 24 Participants | 50 Participants |
| Baseline IGA Score of 3 or 4 IGA Score: 4 | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 24 Participants | 23 Participants | 47 Participants |
| Sex: Female, Male Female | 14 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Male | 14 Participants | 10 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 26 |
| other Total, other adverse events | 16 / 28 | 15 / 26 |
| serious Total, serious adverse events | 0 / 28 | 2 / 26 |
Outcome results
Primary
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
Time frame: Baseline to Week 8
Population: All efficacy analyses were conducted using the Intent to Treat (ITT) Population that consisted of all randomized subjects who were dispensed study drug. Subjects were included in the treatment group to which they were assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diacerein 1% Ointment | Proportion of Subjects Who Achieved ≥ 60% Reduction in Body Surface Area (BSA) of EBS Lesions Within Assessment Area | 16 Participants |
| Vehicle Ointment | Proportion of Subjects Who Achieved ≥ 60% Reduction in Body Surface Area (BSA) of EBS Lesions Within Assessment Area | 14 Participants |
p-value: 0.966695% CI: [0.63, 1.62]Cochran-Mantel-Haenszel
Secondary
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
Time frame: Baseline to Week 8
Population: All efficacy analyses were conducted using the Intent to Treat (ITT) Population that consisted of all randomized subjects who were dispensed study drug. Subjects were included in the treatment group to which they were assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diacerein 1% Ointment | The Proportion of Subjects Who Achieved Success on the Investigator's Global Assessment (IGA) | 12 Participants |
| Vehicle Ointment | The Proportion of Subjects Who Achieved Success on the Investigator's Global Assessment (IGA) | 7 Participants |
p-value: 0.286195% CI: [0.41, 3.28]Cochran-Mantel-Haenszel