Study to Evaluate QR-313 in subjects with Recessive Dystrophic Epidermolysis Bullosa (RDEB) due to mutation(s) in exon 73 of the COL7A1 gene

Phase 1

Conditions: Recessive Dystrophic Epidermolysis Bullosa (RDEB) due to mutation(s) in exon 73 of the COL7A1 gene
MedDRA version: 20.0Level: PTClassification code 10014989Term: Epidermolysis bullosaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2017-004806-17-ES

Lead Sponsor: ProQR Theraputics

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 8

Inclusion Criteria

1. Male or female, = 2 years of age at Screening with a clinical diagnosis of RDEB with confirmation of at least one of the alleles of the COL7A1 gene containing one or more pathogenic mutations in exon 73.
2. Have at least one TWA of 10 x 10 cm that shows dynamic wound healing, no signs of local infection and in which a wound can be selected with the following criteria:
a. a surface area ranging from 5 to 60 cm2
b. open wound that has healing potential
c. exposed sub-epidermal tissue to allow absorption of the IMP
d. no suspicion of current squamous cell carcinoma (SCC) upon visual inspection
Are the trial subjects under 18? yes
Number of subjects for this age range: 7
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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. Untreated carcinoma of the TWA or history of carcinoma within 5 years prior to Screening, except adequately treated cutaneous squamous or basal cell carcinoma.
4. Life expectancy less than 6 months, as assessed by the Investigator
5. 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.
6. Treatment with any systemic immunomodulators, immunosuppressants or cytotoxic chemotherapy within 2 months prior to the Baseline visit.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To evaluate safety and tolerability following topical administration of QR-313 to the target wound area (TWA) <br>- To assess the effect of QR-313 on the exclusion (skipping) of exon 73 from COL7A1 mRNA;Secondary Objective: - To assess the preliminary efficacy on wound healing and skin strength<br>- To assess systemic exposure after topical administration of QR-313 to the Target Wound Area (TWA)<br>- To assess the effect of QR-313 on the presence of collagen type VII protein and anchoring fibrils;Primary end point(s): - Assessment of adverse events/serious adverse events<br>- Absence of exon 73 in COL7A1 mRNA, detected by polymerase chain reaction (PCR);Timepoint(s) of evaluation of this end point: - AEs are assessed throughout the study<br>- Exon skip is assessed after 1 week of treatment with IMP

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Wound size (surface area)<br>- Wound severity as assessed by Physician Subjective Assessment of Severity (PSAS) and Physician Subjective Assessment of Change (PSAC)<br>- Wound status as assessed by Short Wound Specific Questionnaire (SWSQ)<br>- Status of wound closure<br>- Onset of (re)blistering of a healed wound<br>- Serum levels of QR-313<br>- Presence of collagen type VII protein expression, measured by indirect immunofluorescence (IIF) microscopy<br>- Presence of anchoring fibrils measured by transmission electron microscopy (TEM);Timepoint(s) of evaluation of this end point: - weekly images are taken throughout the study for the purpose of the wound healing and skin strength parameters<br>- serum level of QR-313 is measured after 1 week of treatment with IMP<br>- collagen type VII protein expression at 8 weeks after last dose of IMP (EOS)<br>- anchoring fibrils measured at 8 weeks after last dose of IMP (EOS)

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