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Safety and Efficacy of Diacerein 1% Ointment Topical Formulation Compared to Placebo for Subjects With Epidermolysis Bullosa Simplex (EBS)

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ClinicalTrials.gov Identifier: NCT03154333
Recruitment Status : Terminated (An independent data monitoring committee suggested that the study will not meet statistical objectives.)
First Posted : May 16, 2017
Last Update Posted : October 22, 2018
Sponsor:
Information provided by (Responsible Party):
Castle Creek Pharmaceuticals, LLC

May 10, 2017
May 16, 2017
October 22, 2018
June 1, 2017
October 15, 2018   (Final data collection date for primary outcome measure)
Efficacy of Diacerein 1% Ointment compared to Control Ointment based on Reduction in BSA of EBS lesions from Visit 2 (Week 0) to Visit 8 (Week 16) [ Time Frame: Change from Visit 2 (Week 0) to Visit 8 (Week 16) ]
The primary endpoint is the proportion of subjects who achieve ≥40% reduction in BSA of EBS lesions from Visit 2 (Week 0) to Visit 8 (Week 16) to compare the efficacy of Diacerein 1% Ointment to Control 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 BSA will be determined by the investigator and the palmer method will be used to determine BSA of EBS lesion. 1% BSA is defined as the area of the subject's hand held flat, including the thumb and fingers held together.
Efficacy of Diacerein 1% Ointment compared to Control Ointment [ Time Frame: Change from Visit 8 (Week 16) compared to Visit 2 (Week 0) ]
Statistically significant difference between Diacerein 1% ointment and Control ointment in terms of the proportion of subject who achieve treatment success defined as an Investigator's Global Assessment (IGA) grade 0 or 1 at Visit 8 (Week 16) compared to Visit 2 (Week 0) with at least a 2-point reduction in the IGA score.
Complete list of historical versions of study NCT03154333 on ClinicalTrials.gov Archive Site
  • Efficacy of Diacerein 1% Ointment compared to Control Ointment from Visit 2 (Week 0) to Visit 8 (Week 16) [ Time Frame: Change from Visit 2 (Week 0) compared to Visit 8 (Week 16) ]
    Statistically significant difference between Diacerein 1% ointment and Control ointment in terms of the proportion of subject who achieve treatment success defined as an Investigator's Global Assessment (IGA) grade 0 or 1 at Visit 2 (Week 0) compared to Visit 8 (Week 16) with at least a 2-point reduction in the IGA score.
  • Efficacy of Diacerein 1% Ointment compared to Control Ointment based on Reduction in BSA of EBS lesions from Visit 2 (Week 0) to Visit 6 (Week 8) [ Time Frame: Change from Visit 2 (Week 0) compared to Visit 6 (Week 8) ]
    Determine the proportion of subjects who achieve ≥40% reduction in BSA of EBS lesions from Visit 2 (Week 0) to Visit 6 (Week 8) to compare the efficacy of Diacerein 1% Ointment to Control 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 BSA will be determined by the investigator and the palmer method will be used to determine BSA of EBS lesion. 1% BSA is defined as the area of the subject's hand held flat, including the thumb and fingers held together.
  • Efficacy of Diacerein 1% Ointment compared to Control Ointment from Visit 2 (Week 0) to Visit 6 (Week 8) [ Time Frame: Change from Visit 2 (Week 0) compared to Visit 6 (Week 8) ]
    Statistically significant difference between Diacerein 1% ointment and Control ointment in terms of the proportion of subject who achieve treatment success defined as an Investigator's Global Assessment (IGA) grade 0 or 1 at Visit 2 (Week 0) compared to Visit 6 (Week 8) with at least a 2-point reduction in the IGA score.
  • Pain Intensity assessed using the Numeric Rating Scale [ Time Frame: Change from Visit 2 (Week 0) compared to Visit 6 (Week 8) ]
    Pain Intensity will be assessed using the Numeric Rating Scale to describe the pain intensity.The Pain Intensity Assessment is the subject's assessment of pain at its worst experienced over the previous 24 hours on all EBS lesions.
  • Pruritus Intensity assessed using the Numeric Rating Scale [ Time Frame: Change from Visit 2 (Week 0) compared to Visit 6 (Week 8) ]
    Pruritus Intensity will be assessed using the Numeric Rating Scale. The Pruritus Intensity is the subject's, or caregiver's if appropriate, assessment of the average overall intensity of pruritus experienced by the subject over the previous 24 hours on all EBS lesions
  • Mobility Assessment using a series of age-appropriate questions in the eDiary [ Time Frame: Change from Visit 2 (Week 0) compared to Visit 8 (Week 16) ]
    The Mobility Assessment is the subject/caregiver's assessment of the subject's degree of mobility over the previous 24 hours. The subject/caregiver will report the degree of mobility by answering a series of age-appropriate questions in the eDiary.
  • Number of patients with adverse events based on assessment of safety measures [ Time Frame: Change from Visit 8 (Week 16) compared to Visit 2 (Week 0) ]
    Number of patients with adverse events using the following safety measure assessments: demographics\medical history, adverse events and SAEs, vital signs, physical examination, clinical laboratory, and urine pregnancy tests.
  • Number of patients with adverse events based on assessment of safety measures [ Time Frame: Change from Visit 8 (Week 16) compared to Visit 2 (Week 0) ]
    Number of patients with adverse events using the following safety measure assessments: demographics\medical history, adverse events and SAEs, vital signs, physical examination, clinical laboratory, and urine pregnancy tests.
  • Pruritus Intensity assessed using the Numeric Rating Scale [ Time Frame: Change from Visit 8 (Week 16) compared to Visit 2 (Week 0) ]
    Pruritus Intensity will be assessed using the Numeric Rating Scale. The Pruritus Intensity is the subject's, or caregiver's if appropriate, assessment of the average overall intensity of pruritus experienced by the subject over the previous 24 hours on all EBS lesions
  • Pain Intensity assessed using the Numeric Rating Scale or Face Diagram [ Time Frame: Change from Visit 8 (Week 16) compared to Visit 2 (Week 0) ]
    Pain Intensity will be assessed using the Numeric Rating Scale or Face Diagram to describe the pain intensity.
  • Mobility Assessment using a series of age-appropriate questions in the eDiary [ Time Frame: Change from Visit 8 (Week 16) compared to Visit 2 (Week 0) ]
    The Mobility Assessment is the subject/caregiver's assessment of the subject's degree of mobility over the previous 24 hours. The subject/caregiver will report the degree of mobility by answering a series of age-appropriate questions in the eDiary.
  • Reduction in BSA of EBS lesions based on the investigator's assessment [ Time Frame: Change from Visit 8 (Week 16) compared to Visit 2 (Week 0) ]
    The BSA will be determined by the investigator and 1% BSA is defined as the area of the subject's hand held flat, including the thumb and fingers held together.
  • Lesion Surface Area of the Reference Lesion based on the investigator's assessment or photographs [ Time Frame: Change from Visit 8 (Week 16) compared to Visit 2 (Week 0) ]
    The Lesion Surface Area will measure the length and width of the Reference Lesion using a ruler. Length will be measured to the nearest millimeter. Width (the length of the longest axis perpendicular to the length) will be measured to the nearest millimeter.
Not Provided
Not Provided
 
Safety and Efficacy of Diacerein 1% Ointment Topical Formulation Compared to Placebo 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 (EBS) [DELIVERS Study]
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 simplex form is classified by skin blister development in the basal epidermis. Diacerein 1% Ointment is a topical ointment that is being developed for the treatment of EBS. Diacerein in the topical formulation is hydrolyzed to rhein in the epidermis and dermis following administration. Diacerein and rhein have been shown to inhibit the in vitro and in vivo production and activity of interleukin-1β (IL-1β) and other pro-inflammatory cytokines.The purpose of this study is to compare the efficacy of Diacerein 1% Ointment to Control Ointment when applied once-daily for 8 weeks in subjects with EBS.

The proposed study is an international, multicenter, randomized, double-blind, vehicle-controlled, parallel group study to evaluate the safety and efficacy of topical Diacerein 1% Ointment for the treatment of subjects with EBS. Subject randomization will be stratified by genotype (KRT5 and/or KRT14 versus other genotypes) and age group (<8 and ≥8 years old). Participants will be subject to up to 6-week screening period, then be assigned to treat EBS lesions once daily with either Diacerein 1% ointment topical formulation or placebo control ointment for 8 weeks, followed by an 8 week follow-up period. Approximately 80 subjects are planned to be randomized to one of the 2 treatment groups in this study at approximately 20 international investigational centers.

The primary objective of this study is to compare the efficacy of Diacerein 1% Ointment to Control 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 Control Ointment in subjects with EBS in changes in Investigator Global Assessment (IGA) scores, pain, pruritus, mobility, and safety and tolerability.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Epidermolysis Bullosa Simplex
  • Drug: Diacerein 1% Ointment Topical Formulation
    Diacerein 1% Ointment administered topically
  • Drug: Vehicle
    Place ointment administered topically
  • Experimental: Diacerein 1% ointment
    Diacerein 1% ointment topical formulation will be used for 8 weeks
    Intervention: Drug: Diacerein 1% Ointment Topical Formulation
  • Placebo Comparator: A placebo topical ointment
    Placebo topical ointment will be used for 8 weeks
    Intervention: Drug: Vehicle
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
80
Same as current
October 15, 2018
October 15, 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subject is male or female at least 4 years of age at Visit 1
  • Subject has a documented genetic mutation consistent with EBS. A blood or saliva sample will be collected for genetic confirmation if no documented gene mutation data is available. 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 (plantar areas where >25% of the area has hyperkeratosis that has been present for greater than 12 weeks cannot be included as part of the Assessment Area
    • Generalized: arms, legs, torso, hands and feet (scalp, groin and areas where, in the investigator's opinion, the study medication might become occluded cannot be included as part of the Assessment Area)
  • 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 (e.g., medicated cleansers, CBD oil, MediHoney, Silvadine cream 1%, the Investigator should consult the Medical Monitor regarding therapies not specified in the protocol
  • Subject/caregiver agrees to follow topical product application instructions during the treatment period
  • If the subject is a woman of childbearing potential, she has a negative urine pregnancy test and agrees to use an approved effective method of birth control, as defined by this protocol, for the duration of the study.
  • Subject is non-pregnant, non-lactating and is not planning for pregnancy during the study period
  • Subject is in good general health and free of any known disease state or physical condition which, in the investigator's opinion, might impair evaluation of the EBS lesions or which exposes the subject to an unacceptable risk by study participation
  • Subject is willing and able to follow all study instructions and to attend all study visits
  • Subject/caregiver is able to comprehend and willing to sign an Informed Consent and/or Assent Form.

Exclusion Criteria:

  • Subject has EBS lesions to be treated that are infected (i.e., EBS lesions that require therapy to treat an infection)
  • Subject has used any diacerein containing product within 6 months prior to Visit 1
  • Subject has used systemic immunotherapy or cytotoxic chemotherapy within 60 days prior to Visit 1
  • Subject has used systemic steroidal therapy or has used topical steroidal therapy on the EBS lesions to be treated within 30 days prior to Visit 2 (Note: inhaled and ophthalmic products containing steroids are allowed)
  • Subject has evidence of a systemic infection or has used systemic antibiotics within 7 days prior to Visit 1
  • 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 Visit 1. Note: As needed (PRN) use of acetaminophen/paracetamol or NSAIDs within the 4 weeks prior to Visit 1 are permitted provided the treatment was unrelated to EBS symptom relief.
  • Subject has used any systemic diuretics or cardiac glycosides or any systemic product that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application or the study assessments within 30 days prior to Visit 1
  • Subject has used any topical product containing allantoin on the EBS lesions to be treated within 30 days prior to Visit 1
  • Subject has a current malignancy, or a history of treatment for a malignancy within 2 years prior to Visit 1 (Note: does not include non-melanoma skin cancer)
  • Subject currently has diabetes mellitus (HbA1c ≥6.5%); Note: controlled diabetes (HbA1c < 6.5%) is also considered exclusionary
  • Subject has a history of cardiac, hepatic (ALT and or AST >2x ULN, Total bilirubin >1.5x ULN at Visit 1), or renal disease (eGFR<30 ml/min/1.73 m^2) that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application or the study assessments
  • Subject has a non-EBS skin disease (e.g., psoriasis, atopic dermatitis, eczema, sun damage, etc.), or condition (e.g., sunburn) that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application or the study assessments
  • Subject has a history of sensitivity to any of the ingredients in the study medications
  • Subject has participated in an investigational drug trial/device in which administration of an investigational study medication occurred within 30 days prior to Visit 1.
Sexes Eligible for Study: All
4 Years and older   (Child, Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   France,   Germany,   Israel,   Netherlands,   United Kingdom,   United States
 
 
NCT03154333
CCP-020-301
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Castle Creek Pharmaceuticals, LLC
Castle Creek Pharmaceuticals, LLC
Not Provided
Study Director: Amir Tavakkol, MD Castle Creek Pharmaceuticals
Castle Creek Pharmaceuticals, LLC
June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP