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Trial Outcomes & Findings for Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Nonsense Mutation Patients (NCT NCT02698735)

NCT ID: NCT02698735

Last Updated: 2019-10-29

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 for each patient. All treated and untreated sites for all patients were also analyzed to determine statistical significance of treatment versus placebo for topical and intradermal administrations. 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

5 participants

Primary outcome timeframe

3 months

Results posted on

2019-10-29

Participant Flow

A sixth participant in this study (as proposed) was to be a RDEB patient without a nonsense mutation to act as a negative control. Since the patient had no chance to benefit from any treatment, and with the risks/expense/travel/biopsies we decided not to enroll such a patient.

Unit of analysis: Skin test sites

Participant milestones

Participant milestones
Measure
Gentamicin Versus Placebo
Split body skin Test Site study with each patient getting 0.1% topical gentamicin to a test site wound (Test Site #1) or placebo ointment to another like sized wound (Test Site #2) and each patient getting an intradermal injection of gentamicin in an intact skin site (Test Site #3) or an intradermal injection of placebo solution to another intact skin site (Test Site #4). So, there are a total of 4 Test Skin Sites in each patient.
Overall Study
STARTED
5 20
Overall Study
COMPLETED
5 18
Overall Study
NOT COMPLETED
0 2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Nonsense Mutation Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Gentamicin Versus Placebo
n=18 Skin Test Sites
Split body skin Test Site study with each patient getting 0.1% topical gentamicin to a test site wound (Test Site #1) or placebo ointment to another like sized wound (Test Site #2) and each patient getting an intradermal injection of gentamicin in an intact skin site (Test Site #3) or an intradermal injection of placebo solution to another intact skin site (Test Site #4). So, there are a total of 4 Test Skin Sites in each patient.
Age, Categorical
<=18 years
2 Participants
n=93 Participants
Age, Categorical
Between 18 and 65 years
3 Participants
n=93 Participants
Age, Categorical
>=65 years
0 Participants
n=93 Participants
Age, Continuous
21.6 years
n=93 Participants
Sex: Female, Male
Female
2 Participants
n=93 Participants
Sex: Female, Male
Male
3 Participants
n=93 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=93 Participants
Race (NIH/OMB)
Asian
0 Participants
n=93 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=93 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=93 Participants
Race (NIH/OMB)
White
3 Participants
n=93 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=93 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=93 Participants
Region of Enrollment
United States
5 Participants
n=93 Participants
Expression of C7 in Skin
3.78 C7 Expression (% of normal skin)
n=93 Participants
Presence and Definition of Anchoring Fibrils
3 Participants
n=93 Participants

PRIMARY outcome

Timeframe: 3 months

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 for each patient. All treated and untreated sites for all patients were also analyzed to determine statistical significance of treatment versus placebo for topical and intradermal administrations. 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.

Outcome measures

Outcome measures
Measure
Topical Gentamicin Ointment
n=5 Participants
0.1% Gentamicin antibiotic in vehicle ointment
Topical Placebo Ointment
n=5 Participants
Placebo Control (Vehicle ointment alone)
Intradermal Gentamicin Injection
n=4 Participants
8 mg Gentamicin in Solution (200ul Intradermal Injection)
Intradermal Placebo Injection
n=4 Participants
200 ul Placebo Intradermal Injection
Restoration of Full-length Type VII Collagen as Assessed by Immunofluorescence.
5 Fluorescence Intensity (MFI) for C7
Standard Error 55.5
5 Fluorescence Intensity (MFI) for C7
Standard Error 3.5
4 Fluorescence Intensity (MFI) for C7
Standard Error 56.2
4 Fluorescence Intensity (MFI) for C7
Standard Error 2.2

PRIMARY outcome

Timeframe: 3 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). Comparisons were also made between placebo-treated and gentamicin-treated sites.

Outcome measures

Outcome measures
Measure
Topical Gentamicin Ointment
n=5 Participants
0.1% Gentamicin antibiotic in vehicle ointment
Topical Placebo Ointment
n=5 Participants
Placebo Control (Vehicle ointment alone)
Intradermal Gentamicin Injection
n=4 Participants
8 mg Gentamicin in Solution (200ul Intradermal Injection)
Intradermal Placebo Injection
n=4 Participants
200 ul Placebo Intradermal Injection
Number of Participants With Anchoring Fibrils as Assessed by Immuno-electron Microscopy
3 Participants
0 Participants
3 Participants
0 Participants

Adverse Events

Topical Gentamicin Ointment

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Topical Placebo Ointment

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Intradermal Gentamicin Injection

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Intradermal Placebo Injection

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

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place