Recruiting
Phase 1
Phase 2

Gentamicin

Sponsor:

University of Southern California

Code:

NCT04140786

Conditions

Junctional Epidermolysis Bullosa

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

Gentamicin Sulfate, Injectable

Study Details

Brief summary:

Herlitz junctional epidermolysis bullosa (H-JEB), an incurable and fatal inherited skin disease, is caused by loss-of-function mutations in LAMA3, LAMB3 and LAMC2. These mutations result in diminished laminin 332 and epidermal-dermal adherence. 85% of JEB patients have nonsense mutations in LAMA3, LAMB3, or LAMC2, suggesting that H-JEB is a prime therapeutic target for nonsense suppression therapy. The investigators recently demonstrated in three patients that topical gentamicin created new and stable laminin 332 at the dermal-epidermal junction (DEJ), and also improved wound closure and skin quality. Furthermore, these preliminary studies showed that intravenous gentamicin also induced laminin 332 and transiently improved patients' clinical outcomes. No untoward side effects occurred. The investigators propose to optimize the intravenous gentamicin regimen including dosage and infusion schedules to enhance the therapeutic outcome. The milestones will be an increase of laminin 332 in the patients' DEJ, improvement in EB Disease Activity Scores, and no gentamicin-associated side effects.

Conditions

Junctional Epidermolysis Bullosa

Study ID

NCT04140786

Start date

Oct 31, 2019

Status verified date

Nov, 2022

Completion date

Nov 1, 2023

Anticipated

Primary completion date

Nov 1, 2023

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • JEB patients with nonsense mutations in LAMB3 or LAMA3 in either one or two alleles
  • Immunofluorescence (IF) analysis showing absence or decreased laminin 332 expression at their DEJ compared with normal skin.

Exclusion Criteria:

  • Pre-existing known auditory impairment.
  • Pre-existing known renal impairment.
  • Pre-existing known allergies to aminoglycosides or sulfate compounds.
  • Pregnancy.
  • Recent exposure to systemic gentamicin within the past 6 weeks.
  • Current use of any medications with known potential ototoxicity or nephrotoxicity.

Study Design

Enrollment

6 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Daily IV Gentamicin

Once daily (for 24 days) IV infusions of 10 mg/kg gentamicin delivered over a 30-60 minute period.

experimental: Biweekly IV Gentamicin

Twice weekly (for 3 months or 24 total) IV infusions of 10 mg/kg gentamicin delivered over a 30-60 minute period.

Interventions

Gentamicin Sulfate, Injectable

10mg/kg prepared from commercially available stock (typically Kabi Pharmaceuticals) by licensed pharmacists.

Primary outcome measure

  • Laminin 332 Expression in Skin [ Time Frame: 3 months ]
  • Safety (Ototoxicity) [ Time Frame: 3 months ]
  • Safety (Nephrotoxicity) [ Time Frame: 3 months ]
  • Safety (Autoimmune Response) [ Time Frame: 3 months ]

Central Contacts and Locations

Central contacts

David T Woodley, MD

(323) 442 0084dwoodley@med.usc.edu

Locations

University of Southern California

Recruiting

Los Angeles, California, United States, 90033

Contacts

David Woodley, MD

323-865-0956dwoodley@med.usc.edu

Mei Chen, Ph.D

3238650621chenm@usc.edu

More Information

Sponsor

University of Southern California

Last update posted

Nov 3, 2022

Last verified

Nov, 2022

Keywords

  • Nonsense mutation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Southern California on 2022-11-03.