Clinical trial NCT04644627: Topical Gentamicin Nonsense Suppression Therapy of EB
Official title: TOPICAL GENTAMICIN TREATMENT OF PATIENTS WITH EPIDERMOLYSIS BULLOSA DUE TO NONSENSE MUTATIONS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Epidermolysis Bullosa
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2020-11-25
Enrollment: 4
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Wound size reduction
timeFrame: 6 weeks
Secondary outcomes:
measure: Healed skin robustness
timeFrame: 18 weeks
measure: Systemic gentamicin levels
timeFrame: 6 weeks
measure: Protein restoration by gentamicin
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Section of Dermatology, OUS
name: Øystein Sandanger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: