Junctional Epidermolysis Bullosa Non-Herlitz TypePhase 2/3HOLOGENE 5NCT05111600
Open-label, Pivotal Clinical Trial to Confirm Efficacy and Safety of Autologous Grafts Containing Stem Cells Genetically Modified for Epidermis Restoration in Patients With Junctional Epidermolysis Bullosa
A Phase 2/3 study testing Transplantation in people with Junctional Epidermolysis Bullosa Non-Herlitz Type, run by Holostem s.r.l. at 2 sites in 2 countries.
Trial summary
Prospective, multicenter and multinational, open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified transduced with a LAMB3-gamma retroviral vector. Read more about this study
- Who is it for?
- Ages 6 months to 65 years
- Conditions the study is for
- Junctional Epidermolysis Bullosa Non-Herlitz Type
- What is being tested?
- Transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 15 Jul 2022to 22 Nov 2024
- Phase
- Phase 2/3
- 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 months to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Signed and dated informed consent prior to any study-related procedures.
- Male and female patients between 6 months and 65 years old;
- Diagnosis of generalized intermediate LAMB3-dependent JEB, confirmed by NGS or Sanger sequencing and/or immunofluorescence;
- Detectable residual expression of laminin 332 (and its beta-3 chain) by immunofluorescence and/or Western Blot analysis;
- Presence of blisters and/or ≥ 6 cm2 erosions (persistent or recurrent for more than 3 months); the area of the erosion can be considered as the sum of smaller areas in the same body part (i.e. leg, thigh, arm, …)
- A cooperative attitude to follow the study procedures (caregivers in case of children);
- Patients' compliance with the study schedule and procedures, including complete immobilization of the transplanted areas for at least two weeks and hospitalization up to 1 month after transplantation.
Who cannot join
- Known or suspected intolerance to anaesthesia;
- Bad general condition (ECOG index >1);
- Presence of any skin cancers in the area(s) qualified for treatment;
- Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
- Female subjects: Pregnant (as evident by a positive urine hCG or serum-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential [WOCBP]) UNLESS they are willing to use highly effective birth control methods;
- Allergy, sensitivity or intolerance to study medication excipients or other material required by study protocol (as per Investigator's brochure)
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- Contraindications to the local or systemic antibiotics and/or corticosteroids foreseen by the protocol;
- Contraindications to undergo extensive surgical procedures;
- Presence of i) systemic diseases, ii) clinically significant or unstable concurrent disease, iii) other concomitant medical conditions, iv) other clinical contraindications to stem cell transplantation, which based on Investigator's judgment, in consultation with the Sponsor Medical Expert may affect the participation in the study or the 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.
- Previous treatments or clinical trials envisaging the use of cells (including bone marrow transplantation, BMT) and/or both in vivo or ex vivo gene therapy products.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Italy1 site
Struttura Complessa di Dermatologia Azienda Ospedaliero Universitaria Policlinico di Modena
Modena
About this study
Official title: Multicentre, Open-label, Uncontrolled, Pivotal Clinical Trial to Confirm the Efficacy and Safety of Autologous Fibrin-cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified for Restoration of Epidermis in Patients With Junctional Epidermolysis Bullosa
Prospective, multicenter and multinational, open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified transduced with a LAMB3-gamma retroviral vector. The purpose of this study is to demonstrate the safety and efficacy after one or more treatments with genetically corrected cultured epidermal autograft (Hologene 5) for restoration of the epidermis in patients with generalized intermediate LAMB3-dependent Junctional Epidermolysis Bullosa.
Read the detailed description
This trial aims to prove the efficacy and safety of RV-LAMB3-transduced epidermal stem cells and lead to a permanent therapy for the skin lesions affecting JEB patients.
Patients are screened according to the Study Inclusion and Exclusion criteria and if found eligible, participants are candidate for the treatment. After confirmation of eligibility, patients will undergo to biopsy for the collection of the autologous epidermal cells used to produce the tissue for the treatment. If 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 is carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy is processed in a laboratory of a regenerative medicine manufacturing site where the tissue is corrected, expanded and prepared as final sheets to be implanted. Afterward, the patient undergoes to the second intervention when the grafts containing genetically corrected cultured keratinocytes (Hologene-5) are implanted into the selected area under local or general anaesthesia.
The treated area is then immobilized for some days after this surgery. Antibiotics and anti-inflammatory drugs may be administered (if necessary) to prevent infections and to minimise swelling.
The follow-up after implantation is 12 months. The treatment can be repeated. The end of the trial is defined as the last visit of the last patient after the last treatment.
- Being tested
- Transplantation
- Medical subject headings
- Epidermolysis Bullosa, Junctional, Non-Herlitz Type
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TransplantationDrug
Also called Engraftment
Implantation of autologous cultured grafts containing genetically modified stem cells for restoration of functional skin on pre-selected areas
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | After confirmation of eligibility criteria and ICF signature, subject undergoes to skin biopsy for collection of autologous epidermal cells to be used to produce IMP under GMP process. Approximately 2 months later, IMP is transplanted on selected area. Receives: Drug: Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Re-epithelialization
Re-epithelialization in absence of blisters in at least 50% of the transplanted area measured by the Investigator
Measured: 12 months
Protein residual expression
Protein residual expression resulting in 'Yes' or 'Partial' measured by Immunofluorescence
Measured: 12 months
Expression of transgenic mRNA
Expression of transgenic mRNA resulting in 'Yes' or 'Partial' measured by In situ hybridization
Measured: 12 months
Hemidesmosomes presence
Presence of hemidesmosomes measured by electron microscopy
Measured: 12 months
Skin stability
Negativity or positivity at the stripping test
Measured: 12 months
Patient Reported Outcome
Chnage in Patient Reported Outcome score measured by 5-points Likert scale, where: 1=Definitely Worsened, 2=Slightly Worsened, 3=Unchanged, 4=Slightly Improved, 5=Definitely Improved
Measured: 12 months
Secondary outcomes (6)
Re-epithelialization by Independent Assessor
% of re-epithelialization assessed by the Independent Assessor
Measured: 12 months
Quality of Life improvement
Change in EBDASI (Epidermolysis Bullosa Disease Activity and Scarring Index) skin section score, where Best score=0 and Worse score=120 for Activity and Best score=0 and Worse score=84 for Damage
Measured: 12 months
Treatment-emergent adverse events
Number and % of treatment-emergent adverse events
Measured: 12 months
Serious adverse events
Number and % of serious adverse events
Measured: 12 months
Adverse events of special interest
Number and % of adverse events of special interest
Measured: 12 months
Adverse drug reactions
Number and % of adverse drug reactions
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2021
- Study start15 Jul 2022
- Primary completion12 Mar 2024
- Study completion22 Nov 2024
Why it stopped: Development program review and update due to Sponsor re-organization
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Junctional Epidermolysis Bullosa Non-Herlitz TypeStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Holostem s.r.l.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IRCCS San Raffaele, University of Modena and Reggio Emilia
- Responsible party
- Sponsor
- Investigators
- Cristina Magnoni, MD, Surgeon, Principal investigator, Struttura Complessa di Dermatologia Azienda Ospedaliero Universitaria Policlinico di Modena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05111600
- Sponsor's protocol ID
- HTA-HG5-02
- Acronym
- HOLOGENE 5
- Status last verified
- Feb 2025
- First submitted
- 1 Sep 2021
- Last updated
- 19 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre, Open-label, Uncontrolled, Pivotal Clinical Trial to Confirm the Efficacy and Safety of Autologous Fibrin-cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified for Restoration of Epidermis in Patients With Junctional Epidermolysis Bullosa
- ClinicalTrials.gov ID
- NCT05111600
- Acronym / sponsor ID
- HOLOGENE 5 / HTA-HG5-02
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Development program review and update due to Sponsor re-organization
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Holostem s.r.l.Industry (pharma, biotech, devices)
- Collaborators
- IRCCS San Raffaele, University of Modena and Reggio Emilia
- Study start
- 15 Jul 2022 (actual)
- Primary completion
- 12 Mar 2024 (actual)
- Study completion
- 22 Nov 2024 (actual)
- First posted
- 8 Nov 2021 (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.
Prospective, multicenter and multinational, open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified transduced with a LAMB3-gamma retroviral vector. The purpose of this study is to demonstrate the safety and efficacy after one or more treatments with genetically corrected cultured epidermal autograft (Hologene 5) for restoration of the epidermis in patients with generalized intermediate LAMB3-dependent Junctional Epidermolysis Bullosa.
Detailed description
This trial aims to prove the efficacy and safety of RV-LAMB3-transduced epidermal stem cells and lead to a permanent therapy for the skin lesions affecting JEB patients.
Patients are screened according to the Study Inclusion and Exclusion criteria and if found eligible, participants are candidate for the treatment. After confirmation of eligibility, patients will undergo to biopsy for the collection of the autologous epidermal cells used to produce the tissue for the treatment. If 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 is carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy is processed in a laboratory of a regenerative medicine manufacturing site where the tissue is corrected, expanded and prepared as final sheets to be implanted. Afterward, the patient undergoes to the second intervention when the grafts containing genetically corrected cultured keratinocytes (Hologene-5) are implanted into the selected area under local or general anaesthesia.
The treated area is then immobilized for some days after this surgery. Antibiotics and anti-inflammatory drugs may be administered (if necessary) to prevent infections and to minimise swelling.
The follow-up after implantation is 12 months. The treatment can be repeated. The end of the trial is defined as the last visit of the last patient after the last treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: TransplantationAfter confirmation of eligibility criteria and ICF signature, subject undergoes to skin biopsy for collection of autologous epidermal cells to be used to produce IMP under GMP process. Approximately 2 months later, IMP is transplanted on selected area. |
Who may qualify
- Ages
- 6 months to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Signed and dated informed consent prior to any study-related procedures.
- Male and female patients between 6 months and 65 years old;
- Diagnosis of generalized intermediate LAMB3-dependent JEB, confirmed by NGS or Sanger sequencing and/or immunofluorescence;
- Detectable residual expression of laminin 332 (and its beta-3 chain) by immunofluorescence and/or Western Blot analysis;
- Presence of blisters and/or ≥ 6 cm2 erosions (persistent or recurrent for more than 3 months); the area of the erosion can be considered as the sum of smaller areas in the same body part (i.e. leg, thigh, arm, …)
Key exclusion criteria (11 listed)
- Known or suspected intolerance to anaesthesia;
- Bad general condition (ECOG index >1);
- Presence of any skin cancers in the area(s) qualified for treatment;
- Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
- Female subjects: Pregnant (as evident by a positive urine hCG or serum-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential [WOCBP]) UNLESS they are willing to use highly effective birth control methods;
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 |
|---|---|---|
| TransplantationAlso: EngraftmentImplantation of autologous cultured grafts containing genetically modified stem cells for restoration of functional skin on pre-selected areas | Drug | Treatment |
Primary outcome
Re-epithelialization
Time frame: 12 months
Re-epithelialization in absence of blisters in at least 50% of the transplanted area measured by the Investigator
Protein residual expression
Time frame: 12 months
Protein residual expression resulting in 'Yes' or 'Partial' measured by Immunofluorescence
Expression of transgenic mRNA
Time frame: 12 months
Expression of transgenic mRNA resulting in 'Yes' or 'Partial' measured by In situ hybridization
Hemidesmosomes presence
Time frame: 12 months
Presence of hemidesmosomes measured by electron microscopy
Skin stability
Time frame: 12 months
Negativity or positivity at the stripping test
Patient Reported Outcome
Time frame: 12 months
Chnage in Patient Reported Outcome score measured by 5-points Likert scale, where: 1=Definitely Worsened, 2=Slightly Worsened, 3=Unchanged, 4=Slightly Improved, 5=Definitely Improved
6 secondary outcomes
Re-epithelialization by Independent Assessor
Time frame: 12 months
Quality of Life improvement
Time frame: 12 months
Treatment-emergent adverse events
Time frame: 12 months
Serious adverse events
Time frame: 12 months
Adverse events of special interest
Time frame: 12 months
Adverse drug reactions
Time frame: 12 months
Results and safety
The study was stopped early (reason given: Development program review and update due to Sponsor re-organization). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2025.
- Hologene 5: A Phase II/III Clinical Trial of Combined Cell and Gene Therapy of Junctional Epidermolysis BullosaLink provided by the sponsor.
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.
Cristina Magnoni, MD, Surgeon principal investigator
Struttura Complessa di Dermatologia Azienda Ospedaliero Universitaria Policlinico di Modena
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Transplantation in people with Junctional Epidermolysis Bullosa Non-Herlitz Type, run by Holostem s.r.l. at 2 sites in 2 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 7 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 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France, Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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: Development program review and update due to Sponsor re-organization). 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?
Re-epithelialization (time frame: 12 months). The study lists 6 primary outcomes in all. 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 19 Feb 2025.