Topical Gentamicin Nonsense Suppression Therapy of EB

Epidermolysis Bullosa Clinical Trial

— GENTELBULL  

Official title:

TOPICAL GENTAMICIN TREATMENT OF PATIENTS WITH EPIDERMOLYSIS BULLOSA DUE TO NONSENSE MUTATIONS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04644627
• Other study ID #: 105989
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 1, 2020
• Est. completion date: May 1, 2022

Study information

• Verified date: May 2022
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall purpose of this study is to address whether topical gentamicin therapy is an effective and feasible treatment. Specifically, we will investigate the effect of non-intensive treatment (once daily or every other day) on skin protein expression, as well as quantify the effect on wound healing in patients with EB caused by PSC (part A). Furthermore, we will address in vitro whether gentamicin restores protein expression of genes affected by SSM in fibroblasts derived from skin biopsies obtained from patients with EB caused by SSM (part B). If these in vitro experiments yield positive results, the patients donating the cells will be offered to enter part A of this study. The overall duration of part A in this study is planned to be 18 weeks per patients and consists of a 6 weeks treatment period followed by a 12 week follow up period. Each patient will attend 3 study visits: at week 0, week 6 and week 18. All patients will be included within a time period of 12 months. The overall duration of part B will be up to 8 weeks per patients of which 4-7 weeks are spent to prepare fibroblasts obtained from skin biopsies. Then 5 days of in vitro intervention and subsequent analysis follows. Altogether, the duration of the GENTELBULL study will be 78 weeks or less.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: May 1, 2022
• Est. primary completion date: January 11, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. The patient has EB caused by nonsense mutation

2. The patient has a symmetrical distribution of wounds which allows for wounds on one side of the body to serve as control wounds, while study therapy is applied to the other side.

3. The patient (if an adult) or parent(s)/guardian(s) is capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

4. Women of childbearing potential must use a highly effective contraception method

Exclusion Criteria:

1. Known contact allergy against gentamicin sulfate or other ingredients in the ointment

2. Known intolerance to gentamicin sulfate of any sort

3. Moderate or severely reduced kidney function (eGFR <45)

4. Use other experimental therapy against EB

5. Receiving systemic aminoglycosides during the last 3 months

6. The patient uses muscle relaxant drug(s)

Related Conditions & MeSH terms

• Epidermolysis Bullosa

Intervention

Drug:
• Gentamicin Sulfate
Topical gentamicin ointment on wounds once daily for 6 weeks

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Wound size reduction	Mean of ratios for wound areas (measured in cm2) at week 6 to that of week 0 of gentamicin-treated wounds, compared to the corresponding mean of ratios for standard care-treated wounds. The observed effect is considered significant if p<0.05 (unpaired t-test). Of note, each patient may or may not reach the primary end point independent of the other participants	6 weeks
Secondary	Healed skin robustness	Mean of ratios for single wound areas (measured in cm2) at week 18 to that of week 6 of gentamicin-treated wounds, compared to the corresponding mean of ratios for standard care-treated wounds. The observed effect is considered significant if p<0.05 (unpaired t-test). Of note, each patient may or may not reach the primary end point independent of the other participants	18 weeks
Secondary	Systemic gentamicin levels	Trough levels gentamicin in serum day 1 and week 6. If detectable day 1, levels will be monitored more frequently	6 weeks
Secondary	Protein restoration by gentamicin	Immune histochemistry analysis of skin biopsy obtained from healed treated wound area at week 6 and 18 compared to skin biopsy from non-treated non-affected skin obtained at baseline (negative control) and non-affected skin from one healthy control (positive control)	6 weeks