Gentamicin for Junctional Epidermolysis Bullosa

University of Southern California

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Junctional Epidermolysis Bullosa

Treatments: Drug: Gentamicin Sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT03526159

HS-18-00290

Details and patient eligibility

About

Herlitz junctional epidermolysis bullosa (H-JEB), an incurable, fatal, inherited skin disease, is caused by loss-of-function mutations in the LAMA3, LAMB3 or LAMC2 genes, resulting in loss of laminin 332 and poor epidermal-dermal adherence. Eighty percent of H-JEB patients have LAMB3 mutations and about 95% of these are nonsense mutations. The investigators recently demonstrated that gentamicin readily induced nonsense mutation readthrough and produced full-length laminin beta3 in several nonsense mutations tested. Importantly, the gentamicin-induced laminin beta3 restored laminin 332 assembly, secretion, and deposition into the dermal-epidermal junction (DEJ). Newly induced laminin 332 reversed abnormal H-JEB cellular phenotypes. Herein, the investigators propose the first clinical trial of gentamicin (by topical and intravenous administration) in JEB patients with nonsense mutations. The milestones will include restored laminin 332 and hemidesmosomes at the DEJ, improved wound closure, and the absence of significant gentamicin side effects.

Full description

Three subjects (adults and children of any age) will receive topical gentamicin to be applied to select skin sites.

Three subjects (adults and children of any age) will receive intravenous (IV) gentamicin infusions.

Patients will be assessed for Primary and Secondary endpoints during follow up visits.

Enrollment: 6 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. JEB patients with nonsense mutations in the LAMB3 gene in either one or two alleles.

Exclusion criteria

1. JEB patients who do not have nonsense mutations in the LAMB3 gene in either allele.
2. Pre-existing known auditory impairment.
3. Pre-existing known renal impairment.
4. Pre-existing known allergies to aminoglycosides or sulfate compounds.
5. Pregnancy.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Gentamicin Sulfate

Experimental group

Description:

IV Arm: 7.5 mg/kg gentamicin once daily for 14 days. Topical Arm: 0.5% gentamicin ointment applied twice daily for 14 days to selected skin sites.

Treatment:

Drug: Gentamicin Sulfate