Intravenous Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)

NCT ID: NCT03392909

Last Updated: 2022-11-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-05
• Study Completion Date: 2023-12-01

Brief Summary

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable, devastating, inherited skin disease caused by mutations in the COL7A1 gene that encodes for type VII collagen (C7), the major component of anchoring fibrils (AFs), structures that mediate epidermal-dermal adherence. Thirty percent of RDEB patients have nonsense mutations. The investigators recently demonstrated in 5 such patients that intradermal and topical gentamicin induced "read-through" of their nonsense mutations and created robust and sustained new C7 and AFs at the dermal-epidermal junction (DEJ) of their skin and also stimulated wound closure and reduced new blister formation. No untoward side effects occurred. Herein, the investigators propose evaluating the safety and efficacy of intravenous gentamicin in these patients. In theory, this intravenous administration has the possibility of treating simultaneously all of the patients' skin wounds. The milestones will be increased C7 and AFs in the patients' DEJ, improved EB Disease Activity Scores, and absence of gentamicin side effects.

Conditions

Recessive Dystrophic Epidermolysis Bullosa

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravenous Gentamicin

Intravenous gentamicin (7.5 mgs/kg) daily for for either 14 days and then stopped or twice weekly for three months and then stopped.

Group Type: EXPERIMENTAL

Gentamicin

Intervention Type: DRUG

Short-term intravenous gentamicin therapy should have the advantage of treating all of the patient's multiple skin wounds simultaneously. Six patients (three adults and 3 children) will receive intravenous gentamicin (7.5 mgs/kg) daily for 14 days and then stopped. Three adult patients will receive intravenous gentamicin (7.5mg/kg) biweekly for three months and then stopped.

Interventions

Gentamicin

Short-term intravenous gentamicin therapy should have the advantage of treating all of the patient's multiple skin wounds simultaneously. Six patients (three adults and 3 children) will receive intravenous gentamicin (7.5 mgs/kg) daily for 14 days and then stopped. Three adult patients will receive intravenous gentamicin (7.5mg/kg) biweekly for three months and then stopped.

Intervention Type: DRUG

Other Intervention Names

Gentamicin Sulfate

Eligibility Criteria

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 7 and up can participate in the 14 day IV gentamicin trial. Male or female, aged 18 and up can participate in the 3 month IV gentamicin trial.
• Been diagnosed with recessive dystrophic epidermolysis bullosa (RDEB) and with a nonsense mutation in the COL7A1 gene.
• Immunofluorescence evaluation of skin biopsies reveals absence or decreased intensity of C7 expression at their DEJ (dermal epidermal junction) compared with normal human skin biopsies.
• Cultured fibroblasts from patient skin synthesize and secrete full-length, 290kDa C7 alpha chains in the presence of supplemented gentamicin (400 μg/ml in culture).
• Ability to sit or lie down for over 30 minutes for IV infusions. For those in the 3 month trial, to be willing to continue treatment at home under the supervision of licensed and trained infusion nurses.

Exclusion Criteria

• Recent exposure to gentamicin within the past 6 weeks.
• Pre-existing known auditory impairment.
• Pre-existing known renal impairment.
• Pre-existing known allergies to aminoglycosides or sulfate compounds.
• Pregnancy or lactation
• Current use of medications with known ototoxicity or nephrotoxicity.
• Current enrollment in another experimental clinical trial involving systemic treatment with C7 or C7 producing products for the treatment of RDEB.

• Minimum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

David Woodley

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David T. Woodley, MD

Role: PRINCIPAL_INVESTIGATOR

Professor, University of Southern California

Mei Chen, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Professor, University of Southern California

Locations

University of Southern California

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

David T Woodley, MD

Role: CONTACT

dwoodley@usc.edu

626-533-6028

Mei Chen, Ph.D

Role: CONTACT

chenm@usc.edu

323-865-0621

Facility Contacts

David Woodley, MD

Role: primary

dwoodley@usc.edu

323-865-0956

Mei Chen, Ph.D

Role: backup

chenm@usc.edu

323-865-0621

Other Identifiers

HS-17-00995

Identifier Type: -

Identifier Source: org_study_id