Recessive Dystrophic Epidermolysis BullosaPhase 1NCT02493816
Safety Study of Gene-modified Autologous Fibroblasts in Recessive Dystrophic Epidermolysis Bullosa
A Phase 1 study testing Gene-modified autologous fibroblasts in people with Recessive Dystrophic Epidermolysis Bullosa, run by King's College London at 1 site in United Kingdom.
Trial summary
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB. Read more about this study
- Who is it for?
- Ages 17 years and older
- Conditions the study is for
- Recessive Dystrophic Epidermolysis Bullosa
- What is being tested?
- Gene-modified autologous fibroblasts
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2015to Mar 2018
- Phase
- Phase 1
- 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 17 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinical and genetic diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations.
- A reduced number or morphologically abnormal anchoring fibrils confirmed by TEM.
- At least 5x8cm of intact skin on the trunk and/or extremities that is suitable for cell injections.
- Able to undergo local anaesthesia.
- Subjects aged ≥ 17 years and able to give informed consent prior to the first study intervention.
Who cannot join
- Subjects who received other investigational medicinal products within 6 months prior to enrolment into this study.
- Past medical history of biopsy proven skin malignancy.
- Subjects who have received immunotherapy including oral corticosteroids (Prednisolone >1mg/kg) for more than one week (intranasal and topical preparations are permitted) or chemotherapy within 60 days of enrolment into this study.
- Known allergy to any of the constituents of the investigational medicinal product (IMP).
- Subjects with BOTH:
- positive serum antibodies to C7 confirmed by ELISA and
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- positive IIF with binding to the base of salt split skin.
- Subjects who are pregnant or of child-bearing potential who are neither abstinent nor practising an acceptable means of contraception when this is in line with the usual and preferred lifestyle of the subject, as determined by the Investigator, for 12 months after the cell injections.
- Subjects with positive results for HIV, Hepatitis B, Hepatitis C, HTLV or Syphilis.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Guy's and St Thomas' NHS Foundation Trust
London, SE1 9RT
About this study
Official title: Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults With Recessive Dystrophic Epidermolysis Bullosa.
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.
Read the detailed description
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.
This is an open-label single-centre phase I study with primary objective to evaluate the adverse and serious adverse events over 12 months' follow-up period. Secondary objectives include (1) analysis of type VII collagen (C7) expression and morphology of anchoring fibrils in the injected areas of the skin; (2) analysis of immune response to newly expressed C7.
Each study participant will receive three intradermal injections of COL7A1 gene-modified autologous fibroblasts on Day 0 only. Each subject will undergo an initial screening including a physical examination and assessment of disease severity. Blood analyses and skin biopsies will be performed at various time points as per the monitoring schedule over 12 months.
- Being tested
- Gene-modified autologous fibroblasts
- 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.
Gene-modified autologous fibroblastsDrug
Also called COL7A1 gene-modified autologous fibroblasts
3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.
| Study group | Role | What they receive |
|---|---|---|
| Gene-modified autologous fibroblasts | Experimental | 3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only. Receives: Drug: Gene-modified autologous fibroblasts |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over 12 months' follow up period.
Measured: 12 months
Secondary outcomes (5)
Type VII collagen protein expression, measured by direct immunofluorescence, in the treated and untreated skin
Measured: Week 2, Month 3 and Month 12
Morphology of anchoring fibrils, measured by transmission electron microscopy, in the treated and untreated skin
Measured: Week 2, Month 3 and Month 12
Vector copy number, measured by q-PCR, in the treated and untreated skin
Measured: Week 2, Month 3 and Month 12
Anti-type VII collagen antibodies measured by ELISA and indirect immunofluorescence
Measured: Week 2, Month 1, Month 3, Month 6 and Month 12
T-cell responses to full length type VII collagen measured by ELISPOT
Measured: Week 2, Month 1, Month 3, Month 6 and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2015 (estimated)
- Study startSep 2015
- Primary completionMar 2018
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Recessive Dystrophic Epidermolysis BullosaStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London
- Responsible party
- Sponsor
- Investigators
- John A McGrath, FRCP, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02493816
- Sponsor's protocol ID
- LENTICOL-F
- Status last verified
- Aug 2018
- First submitted
- 21 May 2015
- Last updated
- 24 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Wong T, Gammon L, Liu L, Mellerio JE, Dopping-Hepenstal PJ, Pacy J, Elia G, Jeffery R, Leigh IM, Navsaria H, McGrath JA. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2008 Sep;128(9):2179-89. doi: 10.1038/jid.2008.78. Epub 2008 Apr 3.
PubMed 18385758Lwin SM, Syed F, Di WL, Kadiyirire T, Liu L, Guy A, Petrova A, Abdul-Wahab A, Reid F, Phillips R, Elstad M, Georgiadis C, Aristodemou S, Lovell PA, McMillan JR, Mee J, Miskinyte S, Titeux M, Ozoemena L, Pramanik R, Serrano S, Rowles R, Maurin C, Orrin E, Martinez-Queipo M, Rashidghamat E, Tziotzios C, Onoufriadis A, Chen M, Chan L, Farzaneh F, Del Rio M, Tolar J, Bauer JW, Larcher F, Antoniou MN, Hovnanian A, Thrasher AJ, Mellerio JE, Qasim W, McGrath JA. Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. JCI Insight. 2019 Jun 6;4(11):e126243. doi: 10.1172/jci.insight.126243. eCollection 2019 Jun 6.
PubMed 31167965
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults With Recessive Dystrophic Epidermolysis Bullosa.
- ClinicalTrials.gov ID
- NCT02493816
- Acronym / sponsor ID
- LENTICOL-F
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- University College, London
- Study start
- Sep 2015 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 10 Jul 2015 (estimated)
- 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.
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.
Detailed description
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.
This is an open-label single-centre phase I study with primary objective to evaluate the adverse and serious adverse events over 12 months' follow-up period. Secondary objectives include (1) analysis of type VII collagen (C7) expression and morphology of anchoring fibrils in the injected areas of the skin; (2) analysis of immune response to newly expressed C7.
Each study participant will receive three intradermal injections of COL7A1 gene-modified autologous fibroblasts on Day 0 only. Each subject will undergo an initial screening including a physical examination and assessment of disease severity. Blood analyses and skin biopsies will be performed at various time points as per the monitoring schedule over 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gene-modified autologous fibroblasts | Experimental | Drug: Gene-modified autologous fibroblasts3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only. |
Who may qualify
- Ages
- 17 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Clinical and genetic diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations.
- A reduced number or morphologically abnormal anchoring fibrils confirmed by TEM.
- At least 5x8cm of intact skin on the trunk and/or extremities that is suitable for cell injections.
- Able to undergo local anaesthesia.
- Subjects aged ≥ 17 years and able to give informed consent prior to the first study intervention.
Key exclusion criteria (9 listed)
- Subjects who received other investigational medicinal products within 6 months prior to enrolment into this study.
- Past medical history of biopsy proven skin malignancy.
- Subjects who have received immunotherapy including oral corticosteroids (Prednisolone >1mg/kg) for more than one week (intranasal and topical preparations are permitted) or chemotherapy within 60 days of enrolment into this study.
- Known allergy to any of the constituents of the investigational medicinal product (IMP).
- Subjects with BOTH:
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 |
|---|---|---|
| Gene-modified autologous fibroblastsAlso: COL7A1 gene-modified autologous fibroblasts3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only. | Drug | Gene-modified autologous fibroblasts |
Primary outcome
Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over 12 months' follow up period.
Time frame: 12 months
5 secondary outcomes
Type VII collagen protein expression, measured by direct immunofluorescence, in the treated and untreated skin
Time frame: Week 2, Month 3 and Month 12
Morphology of anchoring fibrils, measured by transmission electron microscopy, in the treated and untreated skin
Time frame: Week 2, Month 3 and Month 12
Vector copy number, measured by q-PCR, in the treated and untreated skin
Time frame: Week 2, Month 3 and Month 12
Anti-type VII collagen antibodies measured by ELISA and indirect immunofluorescence
Time frame: Week 2, Month 1, Month 3, Month 6 and Month 12
T-cell responses to full length type VII collagen measured by ELISPOT
Time frame: Week 2, Month 1, Month 3, Month 6 and Month 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Background: PubMed 18385758Wong T, Gammon L, Liu L, Mellerio JE, Dopping-Hepenstal PJ, Pacy J, Elia G, Jeffery R, Leigh IM, Navsaria H, McGrath JA. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2008 Sep;128(9):2179-89. doi: 10.1038/jid.2008.78. Epub 2008 Apr 3.
- Results publication: PubMed 31167965Lwin SM, Syed F, Di WL, Kadiyirire T, Liu L, Guy A, Petrova A, Abdul-Wahab A, Reid F, Phillips R, Elstad M, Georgiadis C, Aristodemou S, Lovell PA, McMillan JR, Mee J, Miskinyte S, Titeux M, Ozoemena L, Pramanik R, Serrano S, Rowles R, Maurin C, Orrin E, Martinez-Queipo M, Rashidghamat E, Tziotzios C, Onoufriadis A, Chen M, Chan L, Farzaneh F, Del Rio M, Tolar J, Bauer JW, Larcher F, Antoniou MN, Hovnanian A, Thrasher AJ, Mellerio JE, Qasim W, McGrath JA. Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. JCI Insight. 2019 Jun 6;4(11):e126243. doi: 10.1172/jci.insight.126243. eCollection 2019 Jun 6.
- 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.
John A McGrath, FRCP principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gene-modified autologous fibroblasts in people with Recessive Dystrophic Epidermolysis Bullosa, run by King's College London at 1 site in United Kingdom.
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 9 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: finished, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over 12 months' follow up period. (time frame: 12 months). 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 NCT02493816, which also lists 2 linked publications.
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 24 Sep 2019.