Phase 2
Completed N=5
Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Nonsense Mutation Patients
Recessive Dystrophic Epidermolysis Bullosa
Source: ClinicalTrials.gov NCT02698735 ↗
Enrolled (actual)
5
Serious AEs
0.0%
Results posted
Aug 2019
Primary outcomePrimary: Restoration of Full-length Type VII Collagen as Assessed by Immunofluorescence. — 5; 5; 4; 4 Fluorescence Intensity (MFI) for C7
Summary
Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable, devastating, inherited skin disease for which there is only supportive care. RDEB is due to mutations in COL7A1 gene that encodes for type VII collagen (C7), the major component of anchoring fibrils (AFs) mediating epidermal-dermal adherence. Approximately 20% of COL7A1 mutations are nonsense mutations leading to premature stop codons and a truncated C7 with diminished function. The investigators demonstrated that aminoglycosides such as gentamicin readily induce premature termination codon (PTC) "read through" and produce biologically functional C7 in 22 reported COL7A1 nonsense mutations. Importantly, aminoglycoside-induced C7 reversed the abnormal RDEB cell phenotype and incorporated into the dermal-epidermal junction. Herein, the investigators propose the first clinical trial of gentamicin (topical and intradermal) in RDEB patients with nonsense mutations that the investigators have fully characterized. The milestones include increased C7 and AFs at the patients' dermal-epidermal junction and absence of significant gentamicin side effects.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Restoration of Full-length Type VII Collagen as Assessed by Immunofluorescence. |
5; 5; 4; 4 | — |
| PRIMARY Number of Participants With Anchoring Fibrils as Assessed by Immuno-electron Microscopy |
3; 0; 3; 0 | — |
Eligibility Criteria
Inclusion Criteria
(i) RDEB patients with a nonsense mutation in COL7A1 in either one or two alleles (ii) An absence or decrease in C7 expression at their DEJ when compared to that of normal human skin.
Exclusion Criteria
(i) Pre-existing renal or auditory impairment (ii) Allergies to aminoglycosides or sulfate compounds (iii) Pregnancy (iv) Exposure to gentamicin within the past 6 weeks.
Data sourced from ClinicalTrials.gov (NCT02698735). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.