Topical QR-313 in Dominant Dystrophic Epidermolysis Bullosa (DDEB) or Recessive Dystrophic Epidermolysis Bullosa (RDEB) Due to Mutation(s) in Exon 73 of the COL7A1gene
Topical QR-313 in Dominant Dystrophic Epidermolysis Bullosa (DDEB) or Recessive Dystrophic Epidermolysis Bullosa (RDEB) Due to Mutation(s) in Exon 73 of the COL7A1gene
A double-blind, randomized, intra-subject placebo-controlled, multicenter, multiple dose
 study, evaluating safety, proof of mechanism, preliminary efficacy and systemic exposure in
 subjects with confirmed DDEB or RDEB diagnosis with one or more pathogenic mutations in exon
 73 in the COL7A1 gene.
This clinical trial will evaluate the safety and tolerability, proof of mechanism, systemic
 exposure and preliminary efficacy following topical application of QR-313 to subjects with
 confirmed DDEB or RDEB with one or more pathogenic mutations in exon 73 in the COL7A1 gene.

 Up to two Target Wound Areas (TWAs) per subject will be selected and randomized. Each TWA
 will be treated with IMP for 8 weeks, either QR-313 or matching placebo. All subjects will
 continue to be followed up for 8 weeks post last dose.

 Subjects will be monitored through home visits and site visits. An imaging system will be
 used to assess the target wound at all home and study site visits.

 QR-313 is a 21-nucleotide antisense oligonucleotide (AON) designed to hybridize to a specific
 sequence in the COL7A1 pre-messengerRNA (pre-mRNA).
Inclusion Criteria:

 1. Male or female, ≥ 4 years of age at Screening with a clinical diagnosis of DDEB or
 RDEB and at least one pathogenic mutation in exon 73 of the COL7A1 gene.

 2. Have at least one TWA, ie, a skin area of 7 x 7 cm that ishows no signs of local
 infection, and contains a target wound that is either new or shows dynamic wound
 healing and complies to the following additional criteria:

 1. surface area of the target wound ranging from 5 to 30 cm2, located centrally in
 the selected 7 x 7 cm TWA.

 2. exposed sub-epidermal tissue to allow absorption of the IMP.

 3. no suspicion of current squamous cell carcinoma (SCC) upon visual inspection.

 Exclusion Criteria:

 1. Pregnant or breast-feeding female

 2. Hemoglobin level at Screening requiring transfusion. The subject may be rescreened
 when the condition is considered stable.

 3. Use of aminoglycosides, by any route of administration, except eye drops, 7 days or 5
 half-lives, whichever is longer, prior to Baseline visit.

 4. Untreated carcinoma of the TWA or history of carcinoma within 5 years prior to
 Screening, except adequately treated cutaneous squamous or basal cell carcinoma.

 5. Life expectancy less than 6 months, as assessed by the Investigator

 6. Current or known history of clinically significant hepatic or renal disease, that in
 the opinion of the Investigator, could impact subject safety or study participation.

 7. Treatment with any systemic immunomodulators, immunosuppressants or cytotoxic
 chemotherapy within 2 months prior to the Baseline visit.

 8. Use of any investigational drug or device within 28 days or 5 half-lives of the
 Baseline visit, whichever is longer, or plans to participate in another study of a
 drug or device during the study period. The washout of 5 half-lives does not apply to
 gene and cell therapy.

 9. Known hypersensitivity to oligonucleotide treatment or excipients of the IMP.

 10. Bleeding disorder or condition requiring the use of anticoagulants to be confirmed by
 aPTT by local lab within 48 hours of first treatment.

 11. Use of systemic or topical steroids within 1 month prior to the baseline visit
 (inhaled and ophthalmic drops of corticosteroids or low dose topical solution of
 budesonide for esophagial strictures may be allowed).