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

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Brief 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

Official 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

Brief Summary

      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.
    

Detailed Description

      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 Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Incidence of treatment emergent adverse events/serious adverse events

Secondary Outcome

 Assessment of wound healing and skin strength measured in surface area (cm2)

Condition

Epidermolysis Bullosa Dystrophica, Recessive

Intervention

QR-313

Study Arms / Comparison Groups

 First TWA (A)
Description:  In each subject up to two target wound areas (TWA) are randomized, one each to active treatment or placebo.
In the first arm; randomization of the first selected TWA to active treatment or placebo

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

2

Start Date

July 2, 2018

Completion Date

December 17, 2018

Primary Completion Date

December 17, 2018

Eligibility 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).
      

Gender

All

Ages

4 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Clinical Operations, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT03605069

Organization ID

PQ-313-002

Secondary IDs

2017-004806-17

Responsible Party

Sponsor

Study Sponsor

Phoenicis Therapeutics


Study Sponsor

Clinical Operations, Study Director, Phoenicis Therapeutics


Verification Date

August 2021