Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Topical QR-313 in Recessive Dystrophic Epidermolysis Bullosa (RDEB) Due to Mutation(s) in Exon 73 of the COL7A1gene (WINGS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03605069
Recruitment Status : Recruiting
First Posted : July 30, 2018
Last Update Posted : April 12, 2019
Sponsor:
Information provided by (Responsible Party):
ProQR Therapeutics

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 RDEB diagnosis with one or more pathogenic mutations in exon 73 in the COL7A1 gene.

Condition or disease Intervention/treatment Phase
Epidermolysis Bullosa Dystrophica, Recessive Drug: QR-313 Drug: Placebo Phase 1 Phase 2

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 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 4 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).


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: intra-subject, placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 RDEB Due to Mutation(s) in Exon 73 of the COL7A1 Gene
Actual Study Start Date : July 2, 2018
Estimated Primary Completion Date : April 17, 2019
Estimated Study Completion Date : April 17, 2019


Arm Intervention/treatment
First TWA (A)

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
QR-313 will be applied topically twice or thrice a week, for 4 weeks of treatment.

Drug: Placebo
Placebo will be applied topically twice or thrice a week, for 4 weeks of treatment.

Second TWA (B)
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
QR-313 will be applied topically twice or thrice a week, for 4 weeks of treatment.

Drug: Placebo
Placebo will be applied topically twice or thrice a week, for 4 weeks of treatment.




Primary Outcome Measures :
  1. Incidence of treatment emergent adverse events/serious adverse events [ Time Frame: through 8 weeks after last dose of IMP (EOS) ]
    Assessment of treatment emergent adverse events/serious adverse events

  2. To assess the effect of QR-313 on the exclusion (skipping) of exon 73 from COL7A1 mRNA [ Time Frame: after 2 or 4 weeks of treatment with IMP ]
    Absence of exon 73 in COL7A1 mRNA, detected by polymerase chain reaction (PCR)


Secondary Outcome Measures :
  1. Assessment of wound healing and skin strength measured in surface area (cm2) [ Time Frame: through 8 weeks after last dose of IMP (EOS) ]
    Wound size (surface area in cm2)

  2. 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) ]
    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

  3. 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) ]
    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.

  4. Assessment of wound healing and skin strength measuring wound area over time, as classified by the WCEI (Wound Care Education Institute) [ Time Frame: through 8 weeks after last dose of IMP (EOS) ]
    Assessment of wound area over time, measured as a percentage of tissue types (slough, eschar, granulation and epithelialization) as classified by the ECWI (Wound Care Education Institute)

  5. Assessment of wound healing and skin strength measuring onset of (re)blistering of a healed wound, as classified by the WCEI (Wound Care Education Institute) [ Time Frame: through 8 weeks after last dose of IMP (EOS) ]
    Onset of (re)blistering of a healed wound

  6. 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) ]
    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.

  7. Assessment of systemic exposure after topical administration of QR-313 to the target wound area (TWA) [ Time Frame: after 2 weeks of treatment and EOS ]
    Serum levels of QR-313

  8. Assessment of the effect of QR-313 on the presence of collagen type VII protein and anchoring fibrils [ Time Frame: at 8 weeks after last dose of IMP (EOS) ]
    Presence of collagen type VII protein expression (IIF microscopy)

  9. Assessment of the effect of QR-313 on the presence of collagen type VII protein and anchoring fibrils [ Time Frame: at 8 weeks after last dose of IMP (EOS) ]
    Presence of anchoring fibrils (TEM)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, ≥ 6 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, ie, a skin area of 10 x 10 cm that shows no signs of local infection, and contains a target wound that shows dynamic wound healing and complies to the following additional criteria:

    1. surface area of the target wound ranging from 5 to 60 cm2, located centrally in the selected 10 x 10 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03605069


Contacts
Layout table for location contacts
Contact: Clinical Trial Manager +31881667000 clinical@proqr.com

Locations
Layout table for location information
United States, California
Stanford University School of Medicine, LPCH Recruiting
Palo Alto, California, United States, 94305
Contact: Kunju Sridhar    650-721-4902    kunju@stanford.edu   
Principal Investigator: Peter Marinkovich, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Kathleen Peoples    720-777-4708    kathleen.peoples@childrenscolorado.org   
Principal Investigator: Anna L Bruckner, MD         
United States, Minnesota
Journey Clinic, Center for Pediatric Blood and Marrow Transplantation Recruiting
Minneapolis, Minnesota, United States, 55454
Contact: Christen Ebens, MD    612-626-8094    ebens012@umn.edu   
Principal Investigator: Christen Ebens, MD         
United States, Ohio
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 15005
Contact: Bret Augsburger    513-803-9009    Bret.Augsburger@cchmc.org   
Principal Investigator: Anne Lucky, MD         
France
Hopital Necker Enfants Malades Recruiting
Paris, France, 75015
Contact: Betty Bosc    +331 44 49 47 44    betty.bosc@aphp.fr   
Principal Investigator: Christine Bodemer, Pr         
Spain
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Rocio Maseda Pedrero, Dr    +34 620 042 691    rociomaseda@gmail.com   
Contact: Vega Mauleón Martínez    +34 912071876    vegamauleon@gmail.com   
Principal Investigator: Rocio Maseda Pedrero, Dr         
Sponsors and Collaborators
ProQR Therapeutics
Investigators
Layout table for investigator information
Study Director: ProQR Study Director ProQR Therapeutics

Additional Information:
Layout table for additonal information
Responsible Party: ProQR Therapeutics
ClinicalTrials.gov Identifier: NCT03605069     History of Changes
Other Study ID Numbers: PQ-313-002
2017-004806-17 ( EudraCT Number )
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ProQR Therapeutics:
Recessive Dystrophic Epidermolysis Bullosa
EB
COL7A1
RNA Therapies
Antisense oligonucleotide
Exon skipping
WINGS
Topical treatment
RDEB
Exon 73
Mutations in exon 73

Additional relevant MeSH terms:
Layout table for MeSH terms
Epidermolysis Bullosa
Epidermolysis Bullosa Dystrophica
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Collagen Diseases
Connective Tissue Diseases