The Study Sponsor, Krystal Biotech, Inc.  conducted a research study to evaluate the safety and effectiveness of an investigational gene therapy, B-VEC, for the treatment of wounds in people with Dystrophic Epidermolysis Bullosa (DEB).B-VEC is a topical gene therapy that is intended to correct the underlying cause of DEB by expressing the collagen VII protein that is missing in DEB patients. B-VEC is the first topical gene therapy being developed for DEB and phase I and phase II clinical trials have been completed. B-VEC has been given to both pediatric and adult participants. There were no drug-related safety events reported during or following these clinical trials and it was confirmed that the full-length collagen VII protein is detected following administration. The intent of this phase III study was to further evaluate the safety of B-VEC and determine whether administration improved wound healing as compared to placebo.

Additional details about the study can be found at this link:  https://clinicaltrials.gov/ct2/show/NCT03536143

Detailed study results can be found at this link: https://www.nejm.org/doi/full/10.1056/NEJMoa2206663

The team at Stanford has investigated gene therapy for RDEB using a participant’s own skin cells for over 30 years. We have completed enrollment for our Phase 1/2a Gene Therapy study. This study involved taking a biopsy of the skin of a participant with RDEB, growing their skin cells in a clean room, inserting the correct gene for type VII collagen into these cells, then grafting these corrected cells onto the participant’s wounds in the operating room.

The initial results of our Phase 1 study were published in the Journal of the American Medical Association (JAMA) in November 2016. Click here to read the full text of this article.

The following images show wounds before and after treatment with these corrected skin sheets.

Long term data (following participants for up to 5 years after grafting) on the Phase 1/2a study was recently published. Click here to read the article.

Briefly, a total of 7 participants underwent treatment in the Phase 1/2a clinical trial with a total of 42 wounds that received treatment. Wounds that were grafted had improved healing compared to control wounds. Treated wounds were more durable and had less pain and less itch than non-treated wounds. Expression of type VII collagen (from the gene that was inserted into skin cells) was seen up to 2 years after grafting. There were no severe adverse events in the study.

Enrollment for the Phase 3 study has began. Click here for more information. 

For more information about our clinical trials and research studies, please click here, or on the Current Studies tab on the left.

Link to clinicaltrials.gov page for Phase 1/2a Gene Therapy Study: https://clinicaltrials.gov/ct2/show/NCT01263379

For information about your rights as a research participant, please contact the Stanford Institutional Review Board (IRB) at (650) 723-5244 or toll-free at 1-866-680-2906.

1988:   Bullous Disease Clinic established at Stanford

1993:   Genetic basis of EB characterized

1996:   First use of gene therapy in mice to correct EB mutations in human skin

2003:   Pre-clinical studies of gene therapy for RDEB in a mouse model

2009:   Approval from Food and Drug Administration (FDA) to start Phase 1 clinical trial

2009:   Initial development of clean room at Stanford for gene therapy graft manufacture

2012:   Approval from Stanford Institutional Review Board for Phase 1 clinical trial 

2013:   First RDEB participant receives genetically corrected skin grafts in Phase 1 trial

2016:   Results of Phase 1 gene therapy clinical trial published in JAMA

2016:   Breakthrough Therapy status awarded by the FDA to RDEB Gene Therapy Trial

EB patients often have severe itch, which leads to scratching, which can worsening wounds. We first investigated how much of a problem itch is in EB patients. We administered a survey and published two articles about itch and EB. The first describes how itch affects EB patients. The second describes different treatments that EB patients use for itch.

We then tried to find new treatments for itch. We investigated a medication called serlopitant for itch in a small pilot study. Results of that study are available here on clinicaltrials.gov and are in press in the Journal of the American Academy of Dermatology.

We are currently conducting a larger study using serlopitant for itch, which is actively enrolling new participants.

Stanford was one of the sites of the National EB Registry, headed by Dr. Fine at Vanderbilt from 1986 until 2002. Dr. Marinkovich served as the Stanford site investigator. This study was instrumental in learning about the effects of EB over time.

Stanford participated as a site in the studies of Zorblisa (also known as SD-101 cream). Results of these studies are available on clinicaltrials.gov:

Phase 2b study: https://clinicaltrials.gov/ct2/show/NCT02014376

Open Label Study for Phase 2b: https://clinicaltrials.gov/ct2/show/NCT02090283

Phase 3 study (with results): https://clinicaltrials.gov/ct2/show/NCT02384460

Open Label Study for Phase 3 (with results): https://clinicaltrials.gov/ct2/show/NCT02670330

Type I Collagen Dressing Study

Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/25557742

Link to clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT01716169

Apligraf Study

Link to clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT00587223

Dermagraft Study

Link to clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT01749306

The Study Sponsor, Krystal Biotech, Inc. conducted a research study to evaluate the safety and effectiveness of an investigational gene therapy, B-VEC, for the treatment of wounds in people with Dystrophic Epidermolysis Bullosa (DEB). B-VEC is a topical gene therapy that is intended to correct the underlying cause of DEB by expressing the collagen VII protein that is missing in DEB patients. B-VEC is the first topical gene therapy being developed for DEB and phase I and phase II clinical trials have been completed. B-VEC has been given to both pediatric and adult participants. There were no drug-related safety events reported during or following these clinical trials and it was confirmed that the full-length collagen VII protein is detected following administration. The intent of this study was to further evaluate the safety of B-VEC and determine whether administration improved wound healing as compared to placebo.

Study results can be found at this link: https://www.nejm.org/doi/full/10.1056/NEJMoa2206663

Additional details about the study can be found at this link:  https://clinicaltrials.gov/ct2/show/NCT03536143