Topical Gentamicin Nonsense Suppression Therapy of EB

NCT04644627 | Completed Phase 1

• 1 other identifier: 105989
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Epidermolysis Bullosa

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Healed skin robustness

  18 weeks

• Systemic gentamicin levels

  6 weeks

• Protein restoration by gentamicin

  6 weeks

Study Arms (1)

Single arm

EXPERIMENTAL

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

Interventions

Gentamicin Sulfate DRUG

Topical gentamicin ointment on wounds once daily for 6 weeks

Single arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has EB caused by nonsense mutation
• 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.
• 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.
• Women of childbearing potential must use a highly effective contraception method

You may not qualify if:

• Known contact allergy against gentamicin sulfate or other ingredients in the ointment
• Known intolerance to gentamicin sulfate of any sort
• Moderate or severely reduced kidney function (eGFR \<45)
• Use other experimental therapy against EB
• Receiving systemic aminoglycosides during the last 3 months
• The patient uses muscle relaxant drug(s)

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, 0424, Norway

Location

MeSH Terms

Conditions

Epidermolysis Bullosa

Interventions

Gentamicins

Condition Hierarchy (Ancestors)

Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vesiculobullous

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Øystein Sandanger, MD, PhD

  Section of Dermatology, OUS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Wound size calculations will be performed on digital photos, the outcome assessor will not know which wounds are treated and which are controls.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Each patient serve as its own control, study treatment is given to one half of the body, the other half receives regular wound treatment. Which side to be treated is determined with randomization.

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: November 25, 2020
• Study Start: December 1, 2020
• Primary Completion: January 11, 2022
• Study Completion: May 1, 2022
• Last Updated: May 3, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)