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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
2
Stanford University School of Medicine, LPCH
Palo Alto, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Journey Clinic, Center for Pediatric Blood and Marrow Transplantation
Minneapolis, Minnesota, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
Hopital Necker Enfants Malades
Paris, France
Hospital Universitario La Paz
Madrid, Spain
Incidence of treatment emergent adverse events/serious adverse events
Assessment of treatment emergent adverse events/serious adverse events
Time frame: through 8 weeks after last dose of IMP (EOS)
To assess the effect of QR-313 on the exclusion (skipping) of exon 73 from COL7A1 mRNA
Absence of exon 73 in COL7A1 mRNA, detected by droplet digital polymerase chain reaction (ddPCR)
Time frame: after 4 weeks of treatment with IMP
Assessment of wound healing and skin strength measured in surface area (cm2)
Wound size (surface area in cm2)
Time frame: through 8 weeks after last dose of IMP (EOS)
Assessment of wound healing and skin strength as assessed by Physician Subjective Assessment of Severity (PSAS)
Wound severity as assessed by Physician Subjective Assessment of Severity (PSAS), a 3-point Likert static scale that classifies a wound in mild, moderate or severe
Time frame: through 8 weeks after last dose of IMP (EOS)
Assessment of wound healing and skin strength as assessed by Physician Subjective Assessment of Change (PSAC)
Wound change in severity as assessed by Physician Subjective Assessment of Change (PSAC), a 3-point Likert static scale that classifies a wound as mild, moderate or severe.
Time frame: through 8 weeks after last dose of IMP (EOS)
Assessment of wound healing and skin strength measuring onset of (re)blistering of a healed wound
Onset of (re)blistering of a healed wound
Time frame: through 8 weeks after last dose of IMP (EOS)
Assessment of wound healing and skin strength as assessed by Short Wound Specific Questionnaire (SWSQ)
Wound status as assessed by Short Wound Specific Questionnaire (SWSQ) addressing three domains: pruritus, pain, and inflammation. Pruritus and pain are recorded as a Patient Reported Outcome (PRO) measure. Inflammation is reported as an Observer Reported Outcome (ObsRO) measure.
Time frame: through 8 weeks after last dose of IMP (EOS)
Assessment of systemic exposure after topical administration of QR-313 to the target wound area (TWA)
Serum levels of QR-313
Time frame: Day 1 and after 4 and 8 weeks of treatment and EOS
Assessment of the effect of QR-313 on the presence of collagen type VII protein and anchoring fibrils
Presence of collagen type VII protein expression (IIF microscopy)
Time frame: after 8 weeks of treatment
Assessment of the effect of QR-313 on the presence of collagen type VII protein and anchoring fibrils
Presence of anchoring fibrils (TEM)
Time frame: after 8 weeks of treatment
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