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

• Register: ClinicalTrials.gov
• Last refreshed on: 30 August 2021
• Main ID: NCT03605069
• Date of registration: 25/06/2018
• Prospective Registration: Yes
• Primary sponsor: Phoenicis Therapeutics
• Public title: 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
• Scientific title: A First in Human, Double-blind, Randomized, Intra-subject Placebo-controlled, Multiple Dose Study of QR-313 Evaluating Safety, Proof of Mechanism, Preliminary Efficacy and Systemic Exposure in Subjects With DDEB or RDEB Due to Mutation(s) in Exon 73 of the COL7A1 Gene
• Date of first enrolment: July 2, 2018
• Target sample size: 2
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03605069
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

France, Spain, United States

Contacts

• Name: Clinical Operations
• Affiliation: Phoenicis Therapeutics

Key inclusion & exclusion criteria

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).



Age minimum: 4 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Epidermolysis Bullosa Dystrophica, Dominant

Epidermolysis Bullosa Dystrophica, Recessive

Intervention(s)

Drug: QR-313

Drug: Placebo

Primary Outcome(s)

Incidence 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 [Time Frame: after 4 weeks of treatment with IMP]

Secondary Outcome(s)

Assessment of systemic exposure after topical administration of QR-313 to the target wound area (TWA) [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 [Time Frame: after 8 weeks of treatment]

Assessment of wound healing and skin strength measured in surface area (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) [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 [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) [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) [Time Frame: through 8 weeks after last dose of IMP (EOS)]

Secondary ID(s)

2017-004806-17

PQ-313-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors