NCT03526159

Gentamicin for Junctional Epidermolysis Bullosa

Recruiting now Phase 1, PHASE2 Last updated 7 April 2020

What this trial tests

Phase 1, PHASE2 trial testing Gentamicin Sulfate in Junctional Epidermolysis Bullosa in 6 participants. Currently enrolling.

Timeline

1 June 2018

Primary endpoint
30 July 2020

31 August 2020

Quick facts

Lead sponsor	University of Southern California
Phase	Phase 1, PHASE2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	6
Start date	1 June 2018
Primary completion	30 July 2020
Estimated completion	31 August 2020
Sites	1 location across United States

Drugs / interventions tested

• Gentamicin Sulfate — full drug profile →

Conditions studied

• Junctional Epidermolysis Bullosa — all drugs for Junctional Epidermolysis Bullosa →

Sponsor

University of Southern California

Who can join

Eligibility, any sex, with Junctional Epidermolysis Bullosa. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Herlitz junctional epidermolysis bullosa (H-JEB), an incurable, fatal, inherited skin disease, is caused by loss-of-function mutations in the LAMA3, LAMB3 or LAMC2 genes, resulting in loss of laminin 332 and poor epidermal-dermal adherence. Eighty percent of H-JEB patients have LAMB3 mutations and about 95% of these are nonsense mutations. The investigators recently demonstrated that gentamicin readily induced nonsense mutation readthrough and produced full-length laminin beta3 in several nonsense mutations tested. Importantly, the gentamicin-induced laminin beta3 restored laminin 332 assembly, secretion, and deposition into the dermal-epidermal junction (DEJ). Newly induced laminin 332 reversed abnormal H-JEB cellular phenotypes. Herein, the investigators propose the first clinical trial of gentamicin (by topical and intravenous administration) in JEB patients with nonsense mutations. The milestones will include restored laminin 332 and hemidesmosomes at the DEJ, improved wound closure, and the absence of significant gentamicin side effects.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Epidermolysis bullosa: Advances in research and treatment.
   Prodinger C, Reichelt J, Bauer JW, Laimer M. · · 2019 · cited 56× · PMID 31140655 · DOI 10.1111/exd.13979
2. Molecular Therapeutics in Development for Epidermolysis Bullosa: Update 2020.
   Has C, South A, Uitto J. · · 2020 · cited 43× · PMID 32328988 · DOI 10.1007/s40291-020-00466-7
3. Gentamicin Induces Laminin 332 and Improves Wound Healing in Junctional Epidermolysis Bullosa Patients with Nonsense Mutations.
   Kwong A, Cogan J, Hou Y, Antaya R, et al · · 2020 · cited 36× · PMID 32222156 · DOI 10.1016/j.ymthe.2020.03.006
4. Molecular and Clinical Outcomes After Intravenous Gentamicin Treatment for Patients With Junctional Epidermolysis Bullosa Caused by Nonsense Variants.
   Mosallaei D, Hao M, Antaya RJ, Levian B, et al · · 2022 · cited 20× · PMID 35234826 · DOI 10.1001/jamadermatol.2021.5992
5. Leading edge: emerging drug, cell, and gene therapies for junctional epidermolysis bullosa.
   Keith AR, Twaroski K, Ebens CL, Tolar J. · · 2020 · cited 17× · PMID 32178539 · DOI 10.1080/14712598.2020.1740678
6. Clinical Perspectives of Gene-Targeted Therapies for Epidermolysis Bullosa.
   Welponer T, Prodinger C, Pinon-Hofbauer J, Hintersteininger A, et al · · 2021 · cited 14× · PMID 34110606 · DOI 10.1007/s13555-021-00561-5
7. Stairways to Advanced Therapies for Epidermolysis Bullosa.
   De Rosa L, Enzo E, Palamenghi M, Sercia L, et al · · 2023 · cited 12× · PMID 36167646 · DOI 10.1101/cshperspect.a041229
8. Challenges in Treating Genodermatoses: New Therapies at the Horizon.
   Morren MA, Legius E, Giuliano F, Hadj-Rabia S, et al · · 2021 · cited 10× · PMID 35069188 · DOI 10.3389/fphar.2021.746664