scholarly journals Hologene 5: A Phase II/III Clinical Trial of Combined Cell and Gene Therapy of Junctional Epidermolysis Bullosa

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura De Rosa ◽  
Elena Enzo ◽  
Giulia Zardi ◽  
Christine Bodemer ◽  
Cristina Magnoni ◽  
...  

Epidermolysis bullosa (EB) is a group of devastating genetic diseases characterized by skin and mucosal fragility and formation of blisters, which develop either spontaneously or in response to minor mechanical trauma. There is no definitive therapy for any form of EB. Intermediate junctional EB (JEB) caused by mutations in the gene LAMB3 has been the first genetic skin disease successfully tackled by ex vivo gene therapy. Here, we present a multicenter, open-label, uncontrolled phase II/III study that aims at confirming the efficacy of Hologene 5, a graft consisting of cultured transgenic keratinocytes and epidermal stem cells and meant to combine cell and gene therapy for the treatment of LAMB3-related JEB. Autologous clonogenic keratinocytes will be isolated from patients’ skin biopsies, genetically corrected with a gamma-retroviral vector (γRV) carrying the full-length human LAMB3 cDNA and plated onto a fibrin support (144cm2). The transgenic epidermis will be transplanted onto surgically prepared selected skin areas of at least six JEB patients (four pediatric and two adults). Evaluation of clinical efficacy will include, as primary endpoint, a combination of clinical parameters, such as percentage of re-epithelialization, cellular, molecular, and functional parameters, mechanical stress tests, and patient-reported outcome (PRO), up to 12months after transplantation. Safety and further efficacy endpoints will also be assessed during the clinical trial and for additional 15years in an interventional non-pharmacological follow-up study. If successful, this clinical trial would provide a therapeutic option for skin lesions of JEB patients with LAMB3 mutations and pave the way to a combined cell and gene therapy platform tackling other forms of EB and different genodermatoses.Clinical Trial Registration: EudraCT Number: 2018-000261-36.

2006 ◽  
Vol 14 (7S_Part_12) ◽  
pp. P677-P677
Author(s):  
Michael J. Castle ◽  
Fernando Calvo Baltanas ◽  
Imre Kovacs ◽  
Alan H. Nagahara ◽  
Krystof S. Bankiewicz ◽  
...  

2000 ◽  
Vol 11 (16) ◽  
pp. 2283-2287 ◽  
Author(s):  
Elena Dellambra ◽  
Graziella Pellegrini ◽  
Liliana Guerra ◽  
Giuliana Ferrari ◽  
Giovanna Zambruno ◽  
...  

2014 ◽  
Vol 2 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Laura De Rosa ◽  
Sonia Carulli ◽  
Fabienne Cocchiarella ◽  
Daniela Quaglino ◽  
Elena Enzo ◽  
...  

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 567-567
Author(s):  
Toru Kono ◽  
Taishi Hata ◽  
Yoshinori Munemoto ◽  
Takanori Matsui ◽  
Hiroshi Kojima ◽  
...  

567 Background: Oxaliplatin-induced peripheral neuropathy (OPN) continues to be a substantial problem for many cancer patients. In light of the promising data on TJ-107 from a previous pilot study (ASCO-GI, 2009), the present clinical trial was conducted to evaluate its efficacy for the prevention of OPN. To determine whether TJ-107 given as an adjuvant therapy effectively prevents oxaliplatin-induced peripheral neuropathy Methods: A phase II, randomized, double-blind, placebo-controlled trial was conducted in colorectal cancer patients undergoing therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX). TJ-107 (7.5g) or matching placebo was orally administered three times daily. The primary endpoint was the incidence of grade 2 or greater OPN according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria after 8 cycles of chemotherapy. Patient-reported neurotoxicity symptoms were also assessed using the neurotoxicity subscale of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx, version 4). Secondary endpoints included the incidence of all grades of OPN after each cycle and chemotherapy response rates. Results: A total of 93 patients were enrolled from May 1, 2009 to March 31, 2010 at 37 participating GONE trial institutions in Japan. Eighty-nine evaluable patients were randomized to either the TJ-107 group (n = 44) or the placebo group (n = 45). Placebo patients showed a significantly higher rate of neurotoxicity than that of TJ-107 patients (p < 0.001), with the median difference in NTX-12 score of 3 and 3.5 at the 8th week and 26th week, respectively. There were no significant between-group differences in response to chemotherapy (55.5% in TJ-107, 39.1% in placebo). In addition, TJ-107 treatment was well tolerated overall. Conclusions: TJ-107 shows promise in reducing the incidence of OPN. Further investigation in a larger phase III trial is necessary before any conclusions can be drawn. [Table: see text]


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