This Phase II clinical study will assess the efficacy, safety and tolerability of topical TolaSure Gel in adults and pediatric patients (2 years of age and older) diagnosed with localized, intermediate, or severe epidermolysis bullosa simplex (EBS). Each patient (40 to complete) will be enrolled in the study and will be randomized to receive either TolaSure Gel or a topical Placebo for daily application for 2-months. After 2-months, all patients will receive TolaSure Gel to daily apply for an additional 2-months. A remote follow-up visit will occur 2-months after the end of study. Total time in the study is 6-months. Localized patients will be applying study medication to their feet, with the option to treat their hands as well throughout the study. Intermediate and severe EBS patients will be applying study medication to randomized treatment area(s) (a minimum of \~2-3% Body Surface Area (BSA)), with the option to treat their feet as well throughout the study.
Patient is a male or female at least 2 years of age.
Patient has a documented diagnosis and confirmed clinical history of localized (previously known as Weber-Cockayne), intermediate (previously Kӧbner), or severe (previously EBS-Dowling Meara) autosomal dominant EBS and/or a genetic mutation in either the KRT14 or KRT5 gene consistent with localized, intermediate, or severe EBS. The Investigator will determine patient eligibility based on historical phenotypic presentation of EBS symptoms along with genetic/diagnosis documentation to determine EBS severity. (If localized, intermediate, or severe EBS is suspected but not diagnosed or genetically confirmed, confirmatory testing will be performed).
Patient must have at least moderate plantar disease activity, defined as ≥15% involvement of the plantar surface of at least one foot, as assessed by clinical examination or standardized imaging, with evidence of active disease (e.g., blisters, erosions, or crusting).
For treatment, the Target Lesional Area (TLA) will consist of daily treating the feet (tops and bottoms) which is approximately 7% body surface area (BSA). Localized EBS subjects will also have the option to treat their hands (tops and bottoms), which is approximately an additional 6% BSA. Palmoplantar evaluation is separate from the intermediate to severe TLA-treated regions per protocol.
Any investigational drug or therapy within 30 days.
Systemic steroidal therapy within 30 days.
Topical steroidal therapy within 14 days (Note: inhaled and ophthalmic products containing steroids are allowed).
Systemic antibiotic therapy within 7 days.
Crossover
5% TolaSure Topical Gel
DrugTolaSure Topical Gel is applied once-daily to designated treatment areas for up to 4 months (Part 2 End of Study).
Topical Placebo Gel
DrugTopical Placebo Gel is applied once-daily to designated treatment areas for up to 2 months (Part 1 End of Study).
Change in Blister Surface Area of the Designated Treatment Area(s)
Clinical photography will be used to assess changes in disease severity within the target lesional area (TLA) and recurrence of blistering by measuring blister surface area in the designated TLA over time.
Plantar Blister Surface Area Reduction
Plantar blister surface area changes over time will be examined using clinical photography for localized EBS patients that treat their feet and those intermediate to severe EBS subjects that opt-in to treat their feet.
Subject-reported Pain Score in Target Lesional Areas During Treatment Application
Using the adult or pediatric PROMIS® Measure form, peak pain during treatment application will be reported on a weekly basis until Part 2 End of Study (EOS, 4-months), with a possible assessment at the 6-month follow up visit. Pain trends in TolaSure Gel, 5% w/w and Placebo groups will be compared. The following PROMIS® Measure forms will be used depending on the patient's age: The Adult Pain Interference-Short Form 8a, Pediatric Pain Interference-Short Form 8a, and Parent Proxy Pain Interference-Short Form 8a. These scales are from 1 to 5 and relate to how much pain interferes with daily activities, with 1 indicating Never/Not at All and 5 indicating Almost Always/Very Much. For 2-4 year-old subjects, worst pain Numeric Rating Scale (NRS) questionnaire will be reported by caregivers/guardians. Pain NRS is from 0 to 10 with 0=no pain and 10=worst pain imaginable.
Subject-reported Itch Score in Target Lesional Area
Using the adult or pediatric PROMIS® Measure form, itch characteristics will be reported on a weekly basis until Part 2 End of Study (EOS, 4-months), with a possible assessment at the 6-month follow up visit. Itch trends in TolaSure Gel, 5% w/w and Placebo groups will be compared. The following PROMIS® Measure forms will be used depending on the patient's age: The Adult Itch Interference-Short Form 8a, Pediatric Itch-Short Form 8a (PIQ-C), and Parent Proxy Itch-Short Form 8a (PIQ-C). These scales are from 1 to 5 and relate to how much itch interferes with daily activities and the level of itch, with 1 indicating Never/No Itch and 5 indicating Almost Always/Very Severe. For 2-4 year-old subjects, worst scratch/itch Numeric Rating Scale (WSI-NRS) questionnaire will be reported by caregivers/guardians. WSI-NRS is from 0 to 10 with 0=no itching or scratching and 10=worst imaginable itching or scratching.
Subject-reported Quality of Life (QoL)
Patient's quality of life (QoL) metrics, highlighting symptoms and daily living concerns of EBS patients, will be reported at Visit 2/ Baseline, Part 1 End of Study (EOS), and Part 2 EOS, with a possible assessment at the 6-month follow up visit. This QoL assessment will be given to patients in a questionnaire format. The questions focus on how EBS blistering areas affect daily physical and social activities as well as mental and emotional health. The scale range is from 0 to 10, with 0 being not at all affected and 10 being severely affected. QoL metrics in TolaSure Gel, 5% w/w and Placebo control groups will be examined.
Blistering and Keratoderma of Hands
Changes to blister surface area and keratoderma over time on the hands of localized EBS subjects will be examined using clinical photography.
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BioMendics, LLC
Lead sponsor
Northwestern University
Collaborator
Ann & Robert H Lurie Children's Hospital of Chicago
Collaborator
Stanford University
Collaborator
Lucile Packard Children's Hospital
Collaborator
