Intravenous Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)

• ClinicalTrials.gov Identifier: NCT03392909
• Recruitment Status: Recruiting
• First Posted: January 8, 2018
• Last Update Posted: November 3, 2022
• Sponsor: University of Southern California
• Information provided by (Responsible Party): David Woodley, University of Southern California

Tracking Information

• First Submitted Date: January 2, 2018
• First Posted Date: January 8, 2018
• Last Update Posted Date: November 3, 2022
• Actual Study Start Date: July 5, 2018
• Estimated Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 2, 2018)

• Full-length type VII collagen expression [ Time Frame: 6 months ]
  Increased expression of full-length type VII collagen as assessed by immunofluorescence
• Generation of anchoring fibrils [ Time Frame: 6 months ]
  Generation of new anchoring fibrils as assessed by immuno-electron microscopy
• Absence of gentamicin side effects [ Time Frame: 6 months ]
  Absence of gentamicin side effects, especially the detection of any ototoxicity or nephrotoxicity

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 2, 2018)

• Improved Disease Activity scores [ Time Frame: 6 months ]
  Improved epidermolysis bullosa Disease Activity scores
• Improved Quality of Life score [ Time Frame: 6 months ]
  Improved Quality of Life score

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Intravenous Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)
• Official Title: Restoration of Full-Length Type VII Collagen in RDEB Patients With Nonsense Mutations After Intravenous Gentamicin Treatment
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recessive Dystrophic Epidermolysis Bullosa

Intervention

Drug: 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.

Other Name: Gentamicin Sulfate

Study Arms

Experimental: 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.

Intervention: Drug: Gentamicin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 2, 2018): 9
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2023
• Estimated Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: David T Woodley, MD; 626-533-6028; dwoodley@usc.edu

Contact: Mei Chen, Ph.D; 323-865-0621; chenm@usc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03392909
• Other Study ID Numbers: HS-17-00995
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: David Woodley, University of Southern California
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Southern California
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: David T. Woodley, MD; Professor, University of Southern California
• Principal Investigator: Mei Chen, Ph.D; Professor, University of Southern California

• PRS Account: University of Southern California
• Verification Date: November 2022