Recessive Dystrophic Epidermolysis BullosaPhase 1/2HOLOGENE7NCT02984085
Clinical Trial to Assess Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified in Patients With RDEB.
A Phase 1/2 study testing Genetically corrected cultured epidermal autograft (ATMP) in people with Recessive Dystrophic Epidermolysis Bullosa, run by Holostem s.r.l. at 1 site in Austria.
Trial summary
Prospective open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified with the aid of a gamma-retroviral vector carrying COL7A1 complementary DNA (cDNA) for restoration of the epidermis in patients with… Read more about this study
- Who is it for?
- Ages 6 to 54 years
- Conditions the study is for
- Recessive Dystrophic Epidermolysis Bullosa
- What is being tested?
- Genetically corrected cultured epidermal autograft (ATMP)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteAustria
- Study dates
- 30 Jan 2017to 6 Aug 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 6 to 54 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Signed and dated informed consent prior to any study-related procedures. Informed consent will also include the possibility of additional transplantations and of the rolling over to the long-term extension period;
- Adult male and female patients (≥18 years old and < 55); Paediatric patients aged 6 to 17 years will be also enrolled.
- RDEB molecular characterization by mutation analysis;
- Non-collagenous domain (NC1 or NC2) antibody immunofluorescence or staining positive in Western Blot;
- Presence of chronic (persistent for more than 3 months) large wounds (>10 cm2) and/or erosion;
- A cooperative attitude to follow up the study procedures (Caregivers in case of minors).
Who cannot join
- Known or suspected intolerances against anaesthesia;
- Bad general condition (ECOG index >1)
- Unresectable or metastasizing squamous cell carcinoma (SCCs);
- Antibodies to type VII collagen associated antigens demonstrated on indirect immunofluorescence;
- Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
- Severe systemic diseases (i.e. uncompensated diabetes);
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- Female subjects: pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they are willing to use one or more reliable methods of contraception with a Pearl index ≤1.
- Allergy, sensitivity or intolerance to drugs or excipients (hypersensitivity to any of the excipients listed in Investigator's brochure or in this protocol):
- Transport medium (Dulbecco's Modified Eagles Medium supplemented with L-glutamine)
- Fibrin support
- Betaisodona
- Contraindications to the local or systemic antibiotics and/ or corticosteroids foreseen by the protocol;
- Contraindications to undergo extensive surgical procedures;
- Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation based upon investigator's judgment or other concomitant medical conditions affecting grafting procedure;
- Patients (or parents in case of paediatric subject) unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study procedures and treatments.
- Participation in another clinical trial where investigational drug was received less than 6 months prior to screening visit.
Trial locations and contacts
1 site in 1 country.
Austria1 site
EB House Austria, Department of Dermatology, Paracelsus Medical University
Salzburg, 5020
About this study
Official title: Prospective, Open-label, Uncontrolled Clinical Trial to Assess the Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified With a Gamma-retroviral (rv) Vector Carrying COL7A1 cDNA for Restoration of Epidermis in Patients With Recessive Dystrophic Epidermolysis Bullosa.
Prospective open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified with the aid of a gamma-retroviral vector carrying COL7A1 complementary DNA (cDNA) for restoration of the epidermis in patients with recessive dystrophic epidermolysis bullosa. The purpose of this study is to demonstrate the safety and efficacy after one or more treatments with genetically corrected cultured epidermal autograft (Hologene 7) in patients suffering of recessive dystrophic epidermolysis bullosa (RDEB) with COL7A1 mutation.
Read the detailed description
This is a monocentric, prospective, open label, uncontrolled clinical trial, phase I/II.
Patients will be screened according to the Study Inclusion and Exclusion criteria and will be candidate for the treatment if all inclusion and none of the exclusion criteria are met.
After confirmation of eligibility, patients will undergo biopsy for the collection of the autologous epidermal cells to be used to produce the tissue for the treatment. In case all criteria are met, the transplantation of the new cultured transgenic epidermis will be planned according to the procedures and the need of the patient.
The study treatment consists of a surgical intervention for new restored stem cells implantation.
The surgery will be carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where they will be corrected, expanded and prepared as final sheets to be implanted. Therefore, the patient can have his second intervention. In this second surgery, genetically corrected cultured epidermal autograft (Hologene 7) will be implanted into the selected area. The specialist surgeon will either use a local or general anaesthetic for the implant operation. The treated area will be immobilized for some days after this operation. Antibiotics and anti-inflammatory drugs will be administered (if necessary) to prevent infections and to minimise swelling.
Three months after the transplantation, primary endpoint will be evaluated by the Investigator. The study completion will be reached when 1 year (secondary endpoint) of follow-up after the last transplant in the last patient will be accomplished.
The end of the trial is defined as the last visit of the last patient after the last treatment if any.
- Being tested
- Genetically corrected cultured epidermal autograft (ATMP)
- Keywords
- RDEB, Stem cells, Gene therapy
- 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.
Genetically corrected cultured epidermal autograft (ATMP)Drug
Also called Hologene 7 Study product (ATMP)
Genetically corrected cultured epidermal autograft (Hologene 7) is intended for transplantation onto surgically prepared blistering skin areas of RDEB patients and permanent regeneration of a healthy, functional and renewing epidermis sustained by the engraftment of transduced epidermal stem cells.
By taking some autologous epidermal cells, a new layer of transgenic tissue is grown in the laboratory. This layer of tissue is then implanted by a surgeon into the damaged area. The implantation can be done in one or more areas and repeated in case of failure of the first surgery.
| Study group | Role | What they receive |
|---|---|---|
| Genetically corrected cultured epidermal autograft | Experimental | The surgery will be carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where they will be corrected, expanded and prepared as final sheets to be implanted.
In the second surgery, genetically corrected cultured epidermal autograft (Hologene 7) will be implanted into the selected area. The specialist surgeon will either use a local or general anaesthetic for the implant operation. The treated area will be immobilized for some days after this operation. Antibiotics and anti-inflammatory drugs will be administered (if necessary) to prevent infections and to minimise swelling. Receives: Drug: Genetically corrected cultured epidermal autograft (ATMP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
number and percentage of patients experiencing treatment-related adverse events (TRAEs), serious adverse events (SAEs) and serious adverse drug reactions (ADRs) up to 3 months after the first treatment.
Measured: 3-month
Secondary outcomes (1)
Efficacy
Percentage of patients with clinical success after one or more treatments with study product at 3 and 12 months follow up.
Clinically success is reached when both the following conditions are met:
- Regeneration of a clinically normal appearing skin with absence of detectable blister.
AND
- Restoration of type VII collagen expression and restoration of anchoring fibrils in the treated area.
Measured: 3- and 12-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2016 (estimated)
- Study start30 Jan 2017
- Primary completion6 Aug 2018
- Study completion6 Aug 2018
Why it stopped: Replaced by new study in progress
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recessive Dystrophic Epidermolysis BullosaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Holostem s.r.l.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Paracelsus Medical University
- Responsible party
- Sponsor
- Investigators
- Michele De Luca, MD/Professor, Study director, Holostem s.r.l.Johann W. Bauer, MD, Principal investigator, Paracelsus Medical University - EB House
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02984085
- Sponsor's protocol ID
- HOLOGENE 7
- Acronym
- HOLOGENE7
- Status last verified
- Feb 2022
- First submitted
- 2 Dec 2016
- Last updated
- 16 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Open-label, Uncontrolled Clinical Trial to Assess the Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified With a Gamma-retroviral (rv) Vector Carrying COL7A1 cDNA for Restoration of Epidermis in Patients With Recessive Dystrophic Epidermolysis Bullosa.
- ClinicalTrials.gov ID
- NCT02984085
- Acronym / sponsor ID
- HOLOGENE7 / HOLOGENE 7
- Keywords
- RDEB, Stem cells, Gene therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Replaced by new study in progress
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Holostem s.r.l.Industry (pharma, biotech, devices)
- Collaborators
- Paracelsus Medical University
- Study start
- 30 Jan 2017 (actual)
- Primary completion
- 6 Aug 2018 (actual)
- Study completion
- 6 Aug 2018 (actual)
- First posted
- 6 Dec 2016 (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.
Prospective open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified with the aid of a gamma-retroviral vector carrying COL7A1 complementary DNA (cDNA) for restoration of the epidermis in patients with recessive dystrophic epidermolysis bullosa. The purpose of this study is to demonstrate the safety and efficacy after one or more treatments with genetically corrected cultured epidermal autograft (Hologene 7) in patients suffering of recessive dystrophic epidermolysis bullosa (RDEB) with COL7A1 mutation.
Detailed description
This is a monocentric, prospective, open label, uncontrolled clinical trial, phase I/II.
Patients will be screened according to the Study Inclusion and Exclusion criteria and will be candidate for the treatment if all inclusion and none of the exclusion criteria are met.
After confirmation of eligibility, patients will undergo biopsy for the collection of the autologous epidermal cells to be used to produce the tissue for the treatment. In case all criteria are met, the transplantation of the new cultured transgenic epidermis will be planned according to the procedures and the need of the patient.
The study treatment consists of a surgical intervention for new restored stem cells implantation.
The surgery will be carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where they will be corrected, expanded and prepared as final sheets to be implanted. Therefore, the patient can have his second intervention. In this second surgery, genetically corrected cultured epidermal autograft (Hologene 7) will be implanted into the selected area. The specialist surgeon will either use a local or general anaesthetic for the implant operation. The treated area will be immobilized for some days after this operation. Antibiotics and anti-inflammatory drugs will be administered (if necessary) to prevent infections and to minimise swelling.
Three months after the transplantation, primary endpoint will be evaluated by the Investigator. The study completion will be reached when 1 year (secondary endpoint) of follow-up after the last transplant in the last patient will be accomplished.
The end of the trial is defined as the last visit of the last patient after the last treatment if any.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Genetically corrected cultured epidermal autograft | Experimental | Drug: Genetically corrected cultured epidermal autograft (ATMP)The surgery will be carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where they will be corrected, expanded and prepared as final sheets to be implanted. In the second surgery, genetically corrected cultured epidermal autograft (Hologene 7) will be implanted into the selected area. The specialist surgeon will either use a local or general anaesthetic for the implant operation. The treated area will be immobilized for some days after this operation. Antibiotics and anti-inflammatory drugs will be administered (if necessary) to prevent infections and to minimise swelling. |
Who may qualify
- Ages
- 6 to 54 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Signed and dated informed consent prior to any study-related procedures. Informed consent will also include the possibility of additional transplantations and of the rolling over to the long-term extension period;
- Adult male and female patients (≥18 years old and < 55); Paediatric patients aged 6 to 17 years will be also enrolled.
- RDEB molecular characterization by mutation analysis;
- Non-collagenous domain (NC1 or NC2) antibody immunofluorescence or staining positive in Western Blot;
- Presence of chronic (persistent for more than 3 months) large wounds (>10 cm2) and/or erosion;
Key exclusion criteria (16 listed)
- Known or suspected intolerances against anaesthesia;
- Bad general condition (ECOG index >1)
- Unresectable or metastasizing squamous cell carcinoma (SCCs);
- Antibodies to type VII collagen associated antigens demonstrated on indirect immunofluorescence;
- Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
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 |
|---|---|---|
| Genetically corrected cultured epidermal autograft (ATMP)Also: Hologene 7 Study product (ATMP)Genetically corrected cultured epidermal autograft (Hologene 7) is intended for transplantation onto surgically prepared blistering skin areas of RDEB patients and permanent regeneration of a healthy, functional and renewing epidermis sustained by the engraftment of transduced epidermal stem cells. By taking some autologous epidermal cells, a new layer of transgenic tissue is grown in the laboratory. This layer of tissue is then implanted by a surgeon into the damaged area. The implantation can be done in one or more areas and repeated in case of failure of the first surgery. | Drug | Genetically corrected cultured epidermal autograft |
Primary outcome
Safety
Time frame: 3-month
number and percentage of patients experiencing treatment-related adverse events (TRAEs), serious adverse events (SAEs) and serious adverse drug reactions (ADRs) up to 3 months after the first treatment.
1 secondary outcome
Efficacy
Time frame: 3- and 12-months
Results and safety
The study was stopped early (reason given: Replaced by new study in progress). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2022.
- Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells.Link provided by the sponsor.
- Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa.Link provided by the sponsor.
- Closure of a large chronic wound through transplantation of gene-corrected epidermal stem cells.Link 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.
Michele De Luca, MD/Professor study director
Holostem s.r.l.
Johann W. Bauer, MD principal investigator
Paracelsus Medical University - EB House
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Genetically corrected cultured epidermal autograft (ATMP) in people with Recessive Dystrophic Epidermolysis Bullosa, run by Holostem s.r.l. at 1 site in Austria.
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 6 inclusion and 16 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 16 Feb 2022. 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 Austria. 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: Replaced by new study in progress). 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?
Safety (time frame: 3-month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Feb 2022.