Trial Outcomes & Findings for Gentamicin for RDEB (NCT NCT03012191)

Last Updated: 2019-07-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

6 participants

Primary outcome timeframe

6 months

Results posted on

2019-07-23

Participant Flow

Participant milestones

Participant milestones
Measure	Topical Gentamicin 0.5% Gentamicin ointment	Intravenous Gentamicin IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	Intradermal Gentamicin 0.5% Gentamicin ointment applied after microneedle roller assistance
Overall Study STARTED	2	2	2
Overall Study COMPLETED	2	2	2
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Gentamicin for RDEB

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Topical Gentamicin n=2 Participants 0.5% Gentamicin ointment	Intravenous Gentamicin n=2 Participants IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	Intradermal Gentamicin n=2 Participants 0.5% Gentamicin ointment applied after microneedle roller assistance
Increased Expression of Full-length Type VII Collagen as Assessed by Immunofluorescence	31.8 C7 Expression (percent of normal skin) Interval 13.7 to 54.0	28.4 C7 Expression (percent of normal skin) Interval 4.0 to 59.0	65.6 C7 Expression (percent of normal skin) Interval 2.0 to 134.0

PRIMARY outcome

Timeframe: 6 months

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).

Outcome measures

Outcome measures
Measure	Topical Gentamicin n=2 Participants 0.5% Gentamicin ointment	Intravenous Gentamicin n=2 Participants IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	Intradermal Gentamicin n=2 Participants 0.5% Gentamicin ointment applied after microneedle roller assistance
Number of Participants With New or Increased Numbers of Anchoring Fibrils as Assessed by Immuno-electron Microscopy	1 Participants	2 Participants	1 Participants

PRIMARY outcome

Timeframe: 6 months

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.

Outcome measures

Outcome measures
Measure	Topical Gentamicin n=2 Participants 0.5% Gentamicin ointment	Intravenous Gentamicin n=2 Participants IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	Intradermal Gentamicin n=2 Participants 0.5% Gentamicin ointment applied after microneedle roller assistance
Number of Participants With Absence of Gentamicin Side Effects Especially the Detection of Any Ototoxicity or Nephrotoxicity	2 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 6 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Topical Gentamicin n=2 Participants 0.5% Gentamicin ointment	Intravenous Gentamicin IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	Intradermal Gentamicin 0.5% Gentamicin ointment applied after microneedle roller assistance
Improved EBDASI Scores	171.3 Scores on a scale Interval 161.0 to 187.0	—	—

Adverse Events

Topical Gentamicin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Intravenous Gentamicin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Intradermal Gentamicin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. David Woodley

University of Southern California Department of Dermatology

Phone: (323)442-0084

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Topical Gentamicin n=2 Participants 0.5% Gentamicin ointment	Intravenous Gentamicin n=2 Participants IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.	Intradermal Gentamicin n=2 Participants 0.5% Gentamicin ointment applied after microneedle roller assistance	Total n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	9 years n=5 Participants	28.5 years n=7 Participants	22 years n=5 Participants	19.8 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	2 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	6 participants n=4 Participants
Expression of C7 in Skin	0 C7 Expression (percent of normal skin) n=5 Participants	6.8 C7 Expression (percent of normal skin) n=7 Participants	5.8 C7 Expression (percent of normal skin) n=5 Participants	4.2 C7 Expression (percent of normal skin) n=4 Participants
Presence of Anchoring Fibrils in Skin	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants