Recruiting
Phase 1
Phase 2

Gentamicin

Sponsor:

University of Southern California

Code:

NCT03526159

Conditions

Junctional Epidermolysis Bullosa

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

Gentamicin Sulfate

Study Details

Brief summary:

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.

Conditions

Junctional Epidermolysis Bullosa

Study ID

NCT03526159

Start date

Jun 1, 2018

Status verified date

Apr, 2020

Completion date

Aug 31, 2020

Anticipated

Primary completion date

Jul 30, 2020

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

6 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Gentamicin Sulfate

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.

Interventions

Gentamicin Sulfate

Gentamicin (formulated as gentamicin sulfate) is a well-known, well-characterized antibiotic that has been used for four decades as a treatment against gram negative bacteria. It, like other aminoglycoside antibiotics, has the well documented added potential to facilitate readthrough of premature termination codons in eukaryotic cells and organisms.

Primary outcome measure

  • Increased laminin beta 3 / laminin 332 expression as assessed by immunofluorescence. [ Time Frame: 3 months ]
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: 3 months ]
  • Generation of new hemidesmosomes as assessed by electron microscopy. [ Time Frame: 3 months ]

Central Contacts and Locations

Central contacts

Mei Chen, Ph.D.

3238650621chenm@usc.edu

David Woodley, M.D.

3238650956dwoodley@usc.edu

Locations

University of Southern California

Recruiting

Los Angeles, California, United States, 90033

Contacts

David Woodley, MD

323-865-0956dwoodley@usc.edu

Mei Chen, Ph.D

323-865-0621chenm@usc.edu

More Information

Sponsor

University of Southern California

Last update posted

Apr 7, 2020

Last verified

Apr, 2020

Keywords

  • Herlitz
  • Laminin 332
  • Laminin beta 3
  • JEB

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Southern California on 2020-04-07.