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

NCT03605069 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: PQ-313-0022017-004806-17
• Study Type: interventional
• Target: 2
• Locations: 3 countries
• Sites: 6

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.

Conditions

Epidermolysis Bullosa Dystrophica, Recessive; Epidermolysis Bullosa Dystrophica, Dominant

Keywords

Recessive Dystrophic Epidermolysis Bullosa; EB; COL7A1; RNA Therapies; Antisense oligonucleotide; Exon skipping; WINGS; Topical treatment; RDEB; Exon 73; Mutations in exon 73; Dominant Dystrophic Epidermolysis Bullosa; DDEB

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment emergent adverse events/serious adverse events

  Assessment of treatment emergent adverse events/serious adverse events

  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)

  after 4 weeks of treatment with IMP

Secondary Outcomes (8)

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

  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)

  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)

  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

  through 8 weeks after last dose of IMP (EOS)

• Assessment of wound healing and skin strength as assessed by Short Wound Specific Questionnaire (SWSQ)

  through 8 weeks after last dose of IMP (EOS)

Study Arms (2)

First TWA (A)

OTHER

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

Drug: QR-313; Drug: Placebo

Second TWA (B)

OTHER

In each subject, in the second arm; allocation of the second selected target wound area (TWA) to the alternative treatment. Second arm in the same subject as the first arm.

Drug: QR-313; Drug: Placebo

Interventions

QR-313 DRUG

QR-313 will be applied topically once daily for 8 weeks of treatment.

First TWA (A); Second TWA (B)

Placebo DRUG

Placebo will be applied topically once daily for 8 weeks of treatment.

First TWA (A); Second TWA (B)

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
• surface area of the target wound ranging from 5 to 30 cm2, located centrally in the selected 7 x 7 cm TWA.
• exposed sub-epidermal tissue to allow absorption of the IMP.
• no suspicion of current squamous cell carcinoma (SCC) upon visual inspection.

You may not qualify if:

• Pregnant or breast-feeding female
• Hemoglobin level at Screening requiring transfusion. The subject may be rescreened when the condition is considered stable.
• Use of aminoglycosides, by any route of administration, except eye drops, 7 days or 5 half-lives, whichever is longer, prior to Baseline visit.
• Untreated carcinoma of the TWA or history of carcinoma within 5 years prior to Screening, except adequately treated cutaneous squamous or basal cell carcinoma.
• Life expectancy less than 6 months, as assessed by the Investigator
• 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.
• Treatment with any systemic immunomodulators, immunosuppressants or cytotoxic chemotherapy within 2 months prior to the Baseline visit.
• 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.
• Known hypersensitivity to oligonucleotide treatment or excipients of the IMP.
• Bleeding disorder or condition requiring the use of anticoagulants to be confirmed by aPTT by local lab within 48 hours of first treatment.
• 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).

Sponsors & Collaborators

• Phoenicis Therapeutics: lead

Study Sites (6)

Stanford University School of Medicine, LPCH

Palo Alto, California, 94305, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Journey Clinic, Center for Pediatric Blood and Marrow Transplantation

Minneapolis, Minnesota, 55454, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 15005, United States

Location

Hopital Necker Enfants Malades

Paris, 75015, France

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Related Publications (1)

• Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.

  PMID: 31215818 DERIVED

MeSH Terms

Conditions

Epidermolysis Bullosa Dystrophica

Condition Hierarchy (Ancestors)

Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vesiculobullous

Study Officials

• Clinical Operations

  Phoenicis Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: intra-subject, placebo-controlled

Study Record Dates

• First Submitted: June 25, 2018
• First Posted: July 30, 2018
• Study Start: July 2, 2018
• Primary Completion: December 17, 2018
• Study Completion: December 17, 2018
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); FR (1); ES (1)