First Human Trial to Evaluate QR-313 for Dystrophic Epidermolysis Bullosa Initiated

Known as “butterfly children,” patients with recessive dystrophic epidermolysis bullosa (RDEB) suffer from a debilitating and painful genetic skin condition characterized by extremely fragile skin and persistent blistering. Aggravated by the slightest bump or rub, RDEB is caused by a mutation in the gene COL7A1, which fails to produce the necessary protein collagen VII, the anchoring fibers that hold the skin together.

While there are currently no approved treatments for the rare skin disease, there are therapies in development, such as ProQR’s RNA therapy, QR-313, which is now being evaluated in its first human clinical trial, dubbed “WINGS.” This past May, Rare Disease Report^® spoke with Daniel de Boer, CEO of ProQR, in an exclusive interview on the novel RNA therapy in development about its promising preclinical display.

“QR-313 is a new therapeutic that is investigational and in clinical studies,” de Boer to Rare Disease Report^®. “It aims to restore normal skin in patients by closing the wounds and restoring normal skin strength. We are developing a so-called oligonucleotide, an RNA therapy; this oligonucleotide is topically applied. It is, basically, a cream that patients put on the skin."

He added that the drug is formulated in that cream, and that the drug gets taken up into the skin where it targets the underlying genetic defect at the RNA level with the goal of restoring normal protein expression, and thus, restore normal, intact skin.

According to de Boer, QR-313 exhibited efficacious behavior in both cellular and in vivo models studied by independent groups and ProQR through its ability to target exon 73 and restore normal COL7A1 function.

WINGS, a double-blind, randomized, intra-subject, placebo-controlled phase 1/2 clinical trial will evaluate the safety, tolerability, and efficacy of QR-313 in patients with RDEB due to mutation(s) in exon 73 of the COL7A1 gene.

Aside from assessing the drug’s safety, tolerability, and efficacy, the trial’s primary objectives will include an assessment of the proof of mechanism (exclusion, or skipping, of exon 73 from COL7A1 mRNA assessed by polymerase chain reaction).

Secondary objectives will include quantifying blood levels of QR-313 and assessing effects on wound healing, skin strength, the presence of the collagen type VII protein, and anchoring fibrils in the skin.

Participating patients at specialized centers in the United States and select European countries will be administered the gel on their wounds approximately every other day for up to 4 weeks with a subsequent 8-week observation period. Additionally, a maximum of 4 small skin biopsies will be performed and tissue will be analyzed for molecular endpoints.

“The initiation of our first human clinical trial for QR-313 is an exciting next step in the development of this novel investigational therapy for DEB,” commented David M. Rodman, MD, executive vice president of research and development at ProQR, in a recent statement.

“WINGS is designed to initially provide molecular proof of mechanism and subsequently clinical proof of concept for QR-313. Now that the study is initiated we expect to dose the first set of adult and pediatric patients over the next few months and provide interim proof of mechanism results late this year,” he added.

Interim proof of mechanism results from the trial are anticipated in 2018, and full clinical proof of concept results from the study are anticipated in 2019. Currently, 8 patients are expected to receive either active gel or placebo on 2 separate wounds. The frequency and/or method of topical delivery may be adjusted depending on the interim analysis results. The rate, strength, and stability of wounds treated with active gel will be compared with those treated with placebo.