Topical Gentamicin Nonsense Suppression Therapy of EB (GENTELBULL)

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

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.

Study Overview

• Status: Completed
• Conditions: Epidermolysis Bullosa
• Intervention / Treatment: Drug: Gentamicin Sulfate

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; Each patient serves as its own control: one half is treated with the study treatment in addition to standard wound therapy, the other half receives standard wound therapy only.	Drug: Gentamicin Sulfate; Topical gentamicin ointment on wounds once daily for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Øystein Sandanger, MD, PhD, Section of Dermatology, OUS

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): January 11, 2022
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): May 3, 2022
• Last Update Submitted That Met QC Criteria: May 1, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases, Vesiculobullous; Skin Abnormalities; Epidermolysis Bullosa; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Gentamicins
• Other Study ID Numbers: 105989

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No