Gentamicin for RDEB

• ClinicalTrials.gov Identifier: NCT03012191
• Recruitment Status: Completed
• First Posted: January 6, 2017
• Results First Posted: July 23, 2019
• Last Update Posted: July 23, 2019
• Sponsor: University of Southern California
• Information provided by (Responsible Party): David Woodley, University of Southern California

• Study Type: Interventional
• 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 Sulfate
• Enrollment: 6

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin
Arm/Group Description	0.5% Gentamicin ointment	IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	0.5% Gentamicin ointment applied after microneedle roller assistance
Period Title: Overall Study
Started	2	2	2
Completed	2	2	2
Not Completed	0	0	0

Baseline Characteristics

Arm/Group Title		Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin	Total
Arm/Group Description		0.5% Gentamicin ointment	IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	0.5% Gentamicin ointment applied after microneedle roller assistance	Total of all reporting groups
Overall Number of Baseline Participants		2	2	2	6
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2 participants	2 participants	2 participants	6 participants
	<=18 years	2 100.0%	0 0.0%	1 50.0%	3 50.0%
	Between 18 and 65 years	0 0.0%	2 100.0%	1 50.0%	3 50.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	2 participants	2 participants	2 participants	6 participants
		9; (1 to 17)	28.5; (27 to 30)	22; (17 to 27)	19.8; (1 to 30)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2 participants	2 participants	2 participants	6 participants
	Female	0 0.0%	1 50.0%	1 50.0%	2 33.3%
	Male	2 100.0%	1 50.0%	1 50.0%	4 66.7%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2 participants	2 participants	2 participants	6 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	2 100.0%	2 100.0%	2 100.0%	6 100.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	2 participants	2 participants	2 participants	6 participants
		2	2	2	6
Expression of C7 in Skin; Mean (Full Range); Unit of measure: C7 Expression (percent of normal skin)
	Number Analyzed	2 participants	2 participants	2 participants	6 participants
		0; (0 to 0)	6.8; (2 to 11.6)	5.8; (0 to 11.6)	4.2; (0 to 11.6)
Presence of Anchoring Fibrils in Skin; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2 participants	2 participants	2 participants	6 participants
		0 0.0%	1 50.0%	1 50.0%	2 33.3%

Outcome Measures

1. Primary Outcome

Title	Increased Expression of Full-length Type VII Collagen as Assessed by Immunofluorescence
Description	The expression of type VII collagen at the patients' dermal-epidermal junction was assessed by immunofluorescence (IF) using an antibody specific to type VII collagen. The expression was semi-quantitated using NIH Image J software. The IF expression of type VII collagen was assessed before treatment and at one and three months after treatment. At each assessment time point, type VII collagen expression was also measured in normal human skin. The expression of type VII collagen was then expressed as a percentage of the type VII collagen expressed in normal human skin.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin
Arm/Group Description:	0.5% Gentamicin ointment	IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	0.5% Gentamicin ointment applied after microneedle roller assistance
Overall Number of Participants Analyzed	2	2	2
Mean (Full Range); Unit of Measure: C7 Expression (percent of normal skin)
	31.8; (13.7 to 54.0)	28.4; (4.0 to 59.0)	65.6; (2 to 134)

2. Primary Outcome

Title	Number of Participants With New or Increased Numbers of Anchoring Fibrils as Assessed by Immuno-electron Microscopy
Description	The expression of anchoring fibril structures at the patients' dermal-epidermal junction was assessed by immuno-electron microscopy (IEM) using an antibody specific to type VII collagen. The IEM expression of anchoring fibrils was assessed before treatment and at one and three months after treatment. At each assessment time point, anchoring fibrils were compared with normal human skin. Baseline pre-treatment and one and three month post-treatment sites were compared for the presence of anchoring fibrils after gentamicin treatment (or increase if anchoring fibrils were detected at baseline in patients).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin
Arm/Group Description:	0.5% Gentamicin ointment	IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	0.5% Gentamicin ointment applied after microneedle roller assistance
Overall Number of Participants Analyzed	2	2	2
Measure Type: Count of Participants; Unit of Measure: Participants
	1 50.0%	2 100.0%	1 50.0%

3. Primary Outcome

Title	Number of Participants With Absence of Gentamicin Side Effects Especially the Detection of Any Ototoxicity or Nephrotoxicity
Description	Prolonged exposure to systemic gentamicin is associated with ototoxicity and nephrotoxicity. Specific tests (creatinine clearance and gold-tone audiometry) are performed throughout the study in order to detect any drug-specific adverse events as a result of systemic exposure to gentamicin. Additionally, we test patient skin and serum throughout the study to look for increase of autoantibodies to C7. Since some of these patients may have never had C7 expressed in their bodies, gentamicin-induced C7 may cause in auto-immune response.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin
Arm/Group Description:	0.5% Gentamicin ointment	IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	0.5% Gentamicin ointment applied after microneedle roller assistance
Overall Number of Participants Analyzed	2	2	2
Measure Type: Count of Participants; Unit of Measure: Participants
	2 100.0%	2 100.0%	2 100.0%

4. Secondary Outcome

Title	Improved EBDASI Scores
Description	EBDASI - Epidermolysis Bullosa Disease Activity and Scarring Index Scale - Minimum (0) to Maximum (506) A lower score indicates a better outcome (less disease activity and/or damage) A clinical tool for evaluating the disease activity and damage associated with bullous patients. To be administered by a licensed dermatologist.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

EBDASI is a system-wide disease activity score used for participants in the Intravenous Gentamicin phase of the study. Participants receiving Topical and Intradermal Gentamicin were not administered the EBDASI.

Arm/Group Title	Intravenous Gentamicin
Arm/Group Description:	IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.
Overall Number of Participants Analyzed	2
Mean (Full Range); Unit of Measure: Scores on a scale
	171.3; (161 to 187)

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin
Arm/Group Description	0.5% Gentamicin ointment	IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	0.5% Gentamicin ointment applied after microneedle roller assistance
All-Cause Mortality
	Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/2 (0.00%)	0/2 (0.00%)	0/2 (0.00%)
Serious Adverse Events
	Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/2 (0.00%)	0/2 (0.00%)	0/2 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Topical Gentamicin	Intravenous Gentamicin	Intradermal Gentamicin
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/2 (0.00%)	0/2 (0.00%)	0/2 (0.00%)

Limitations and Caveats

Small number of subjects analyzed due to rarity of the disease and experimental plan.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. David Woodley
• Organization: University of Southern California Department of Dermatology
• Phone: (323)442-0084
• EMail: dwoodley@med.usc.edu

• Responsible Party: David Woodley, University of Southern California
• ClinicalTrials.gov Identifier: NCT03012191
• Other Study ID Numbers: HS-16-00788
• First Submitted: January 4, 2017
• First Posted: January 6, 2017
• Results First Submitted: June 3, 2019
• Results First Posted: July 23, 2019
• Last Update Posted: July 23, 2019