Safety and Efficacy of Topical TolaSure Targeting Aggregated Mutant Keratin in Severe Epidermolysis Bullosa Simplex

NCT05062070 | Completed Phase 1 FDA Drug

• 1 other identifier: TAMES-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

TolaSure is a topical gel for the promotion of accelerated wound healing. This Phase I study will assess the safety, tolerability, and clinical effects of TolaSure when applied to wounded skin areas of patients diagnosed with severe epidermolysis bullosa simplex (i.e., EBS-Dowling Meara). A total of 10, severe EBS patients, males and females ages 18 years and older, will be enrolled. Patients will apply TolaSure and Vehicle Gel once-daily for a maximum of 10 weeks.

Conditions

Epidermolysis Bullosa Simplex

Keywords

Epidermolysis Bullosa; Epidermolysis Bullosa Simplex; EBS; Severe EBS; EBS Dowling-Meara; Skin Diseases; Suction Blister; Skin Abnormalities; Keratin; Aggregate; Mutant; EBS-DM

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  Safety monitoring will include clinical chemistry tests, physical examinations (including assessment of Treatment and Suction Blister Areas), and vital sign measurements. These assessments along with AE reviews will identify potential TEAEs.

  Day 1, Day 2, then Weekly until End of Study (maximum 10 weeks)

Secondary Outcomes (6)

• Investigator Global Assessment (IGA)

  Day 1, Day 2, then Weekly until End of Study (maximum 10 weeks)

• Keratin Aggregate Counts and Cell Morphology Assessment

  Day 1, During Study (optional, estimated Week 3-Week 6), End of Study (maximum 10 weeks)

• Suction Blister Time

  Day 1 and End of Study (maximum 10 weeks)

• Patient's-reported Overall Impression Score of Treatment Areas

  Day 1, then Weekly until End of Study (maximum 10 weeks)

• Patient's-reported Pain Score of Treatment Areas

  Day 1, then Weekly until End of Study (maximum 10 weeks)

Other Outcomes (2)

• Proportion of Keratinocytes containing Autophagosomes

  Day 1, During Study (optional, estimated Week 3-Week 6), End of Study (maximum 10 weeks)

• Cytokine Content in Suction Blister Fluid

  Day 1 and End of Study (maximum 10 weeks)

Study Arms (2)

5 Percent TolaSure Topical Gel

ACTIVE COMPARATOR

5% (w/w) TolaSure Gel

Drug: TolaSure Topical Gel

Topical Vehicle Gel

PLACEBO COMPARATOR

TolaSure Vehicle Gel

Drug: Vehicle Topical Gel

Interventions

TolaSure Topical Gel DRUG

TolaSure Topical Gel is applied once-daily for up to 10 weeks to designated Treatment Area and Suction Blister Area.

Also known as: Active Ingredient BM-3103

5 Percent TolaSure Topical Gel

Vehicle Topical Gel DRUG

TolaSure Vehicle Gel is applied once-daily for up to 10 weeks to designated Treatment Area and Suction Blister Area.

Also known as: TolaSure Vehicle Gel

Topical Vehicle Gel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is a male or female at least 18 years of age.
• Patient has a documented genetic mutation in either the keratin 14 (K14) or keratin 5 (K5) gene and that their EBS diagnosis and/or specific mutation are consistent with severe EBS (previously EBS-DM). (If severe EBS is suspected but not genetically confirmed, confirmatory testing will be performed).
• Patient possesses the four required skin areas:
• Treatment Areas:
• Must have two (2) Treatment Areas defined as an IGA score ≥ 3. Treatment Areas may have defined erosions, erythema, and ulcerations.
• Must be comparable in size with an area of approximately 300-400 cm\^2 per area. Individually, a treatment area may be continuous or non-contiguous and must contain newly-formed blisters/erosions. Ideally, the two Treatment Areas on the patient should not be adjacent to each other and should be located bilaterally and roughly symmetrically on the trunk, abdomen, or upper or lower extremities.
• May not be infected (as assessed by the Principal Investigator) or have been treated with a topical antibiotic within 14 days.
• May not be located on palms, soles, scalp, groin, and any other areas that the Principal Investigator believes there will be difficulty in applying treatments and bandaging or assessing outcome measures.
• Suction Blister Areas (SBAs):
• Must have two (2) areas of non-wounded and visually uninvolved skin, defined as an IGA score of zero (0).
• Must be comparable in size (approximately 50 cm\^2)
• If the patient is a woman of childbearing potential (WOCBP),
• Has a negative urine pregnancy test.
• Agrees to use an approved effective form of birth control with failure rates \<1% per year (e.g., implant, injectable, combined oral contraceptive, intrauterine contraceptive device, sexual abstinence, vasectomized partner) during participation in the study (and at least 3 months thereafter).
• Is not nursing.

You may not qualify if:

• Patient's use of prior or concomitant medication or medical treatments/procedures:
• Any investigational drug 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.
• Systemic diuretics or cardiac glycosides within 30 days.
• Currently receiving chemotherapy or radiation.
• Patient has undergone stem cell transplant or gene therapy for the treatment of inherited EB.
• Surgery within the previous 3 months (except for minor cosmetic or dental procedures).
• Patient's medical history includes:
• Cancer that is currently undergoing treatment.
• History of severe vitamin, mineral, or protein deficiency.
• Current systemic infection.
• HIV/AIDS.
• 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.

Sponsors & Collaborators

• BioMendics, LLC: lead

Study Sites (1)

Stanford University School of Medicine, Dermatology Department

Redwood City, California, 94063, United States

Location

MeSH Terms

Conditions

Epidermolysis Bullosa Simplex; Epidermolysis Bullosa; Skin Diseases; Skin Abnormalities

Condition Hierarchy (Ancestors)

Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin and Connective Tissue Diseases; Skin Diseases, Vesiculobullous

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: September 30, 2021
• Study Start: May 5, 2022
• Primary Completion: June 22, 2023
• Study Completion: June 22, 2023
• Last Updated: September 11, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)