Epidermolysis Bullosa Dystrophica, RecessivePhase 1/2NCT03605069
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
A Phase 1/2 study testing QR-313 in people with Epidermolysis Bullosa Dystrophica, Recessive and Epidermolysis Bullosa Dystrophica, Dominant, run by Phoenicis Therapeutics at 6 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Epidermolysis Bullosa Dystrophica, Recessive, Epidermolysis Bullosa Dystrophica, Dominant
- What is being tested?
- QR-313
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 2 Jul 2018to 17 Dec 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States4 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Cincinnati Children's Hospital
Cincinnati, Ohio, 15005
Journey Clinic, Center for Pediatric Blood and Marrow Transplantation
Minneapolis, Minnesota, 55454
Stanford University School of Medicine, LPCH
Palo Alto, California, 94305
About this study
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
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.
Read the 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).
- Being tested
- QR-313, Placebo
- 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
- Medical subject headings
- Epidermolysis Bullosa Dystrophica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QR-313Drug
QR-313 will be applied topically once daily for 8 weeks of treatment.
PlaceboDrug
Placebo will be applied topically once daily for 8 weeks of treatment.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: QR-313; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment emergent adverse events/serious adverse events
Assessment of treatment emergent adverse events/serious adverse events
Measured: 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)
Measured: after 4 weeks of treatment with IMP
Secondary outcomes (8)
Assessment of wound healing and skin strength measured in surface area (cm2)
Wound size (surface area in cm2)
Measured: 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)
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
Measured: 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)
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.
Measured: 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
Onset of (re)blistering of a healed wound
Measured: through 8 weeks after last dose of IMP (EOS)
Assessment of wound healing and skin strength as assessed by Short Wound Specific Questionnaire (SWSQ)
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.
Measured: through 8 weeks after last dose of IMP (EOS)
Assessment of systemic exposure after topical administration of QR-313 to the target wound area (TWA)
Serum levels of QR-313
Measured: 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
Presence of collagen type VII protein expression (IIF microscopy)
Measured: after 8 weeks of treatment
Assessment of the effect of QR-313 on the presence of collagen type VII protein and anchoring fibrils
Presence of anchoring fibrils (TEM)
Measured: after 8 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2018
- Study start2 Jul 2018
- Primary completion17 Dec 2018
- Study completion17 Dec 2018
Why it stopped: Low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Epidermolysis Bullosa Dystrophica, RecessiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- intra-subject, placebo-controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Phoenicis Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Operations, Study director, Phoenicis Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03605069
- Sponsor's protocol ID
- PQ-313-002
- Other IDs
- 2017-004806-17, 2017
- Status last verified
- Aug 2021
- First submitted
- 25 Jun 2018
- Last updated
- 25 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31215818
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03605069
- Acronym / sponsor ID
- PQ-313-002
- Keywords
- Recessive Dystrophic Epidermolysis Bullosa, EB, COL7A1, RNA Therapies, Antisense oligonucleotide, Exon skipping, WINGS, Topical treatment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Phoenicis TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 2 Jul 2018 (actual)
- Primary completion
- 17 Dec 2018 (actual)
- Study completion
- 17 Dec 2018 (actual)
- First posted
- 30 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- intra-subject, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| First TWA (A) | Other | Drug: QR-313, Drug: PlaceboIn 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 |
| Second TWA (B) | Other | Drug: QR-313, Drug: PlaceboIn 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. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QR-313QR-313 will be applied topically once daily for 8 weeks of treatment. | Drug | First TWA (A), Second TWA (B) |
| PlaceboPlacebo will be applied topically once daily for 8 weeks of treatment. | Drug | First TWA (A), Second TWA (B) |
Primary outcome
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
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
Absence of exon 73 in COL7A1 mRNA, detected by droplet digital polymerase chain reaction (ddPCR)
8 secondary outcomes
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 as assessed by Physician Subjective Assessment of Change (PSAC)
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 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 the effect of QR-313 on the presence of collagen type VII protein and anchoring fibrils
Time frame: after 8 weeks of treatment
Results and safety
The study was stopped early (reason given: Low enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Derived from this study: PubMed 31215818Miah 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.
- company websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Operations study director
Phoenicis Therapeutics
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing QR-313 in people with Epidermolysis Bullosa Dystrophica, Recessive and Epidermolysis Bullosa Dystrophica, Dominant, run by Phoenicis Therapeutics at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment emergent adverse events/serious adverse events (time frame: through 8 weeks after last dose of IMP (EOS)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03605069, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.