ClinicalTrials.gg
TerminatedNCT05111600HOLOGENE 5Updated Feb 19, 2025

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 interventional study of Transplantation in Junctional Epidermolysis Bullosa Non-Herlitz Type, sponsored by Holostem s.r.l.. Terminated at 2 sites in 2 countries. Open to participants aged 6 Months to 65 Years. Per ClinicalTrials.gov, last updated 2025-02-19.

Sponsored by Holostem s.r.l. · Phase 2/3, Interventional, and Treatment

Why this study was terminated
Development program review and update due to Sponsor re-organization
Phase
Phase 2/3
Study type
Interventional
Enrollment
2
Allocation
Not applicable
Ages
6 Months to 65 Years
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Junctional Epidermolysis Bullosa Non-Herlitz Type
03

In context

Lead sponsor

Holostem s.r.l. is the lead sponsor of 6 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Months to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Signed and dated prior to any study-related procedures.
  2. Male and female patients between 6 months and 65 years old;
  3. Diagnosis of generalized intermediate LAMB3-dependent JEB, confirmed by NGS or Sanger sequencing and/or immunofluorescence;
  4. Detectable residual expression of laminin 332 (and its beta-3 chain) by immunofluorescence and/or Western Blot analysis;
  5. 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, ...)
  6. A cooperative attitude to follow the study procedures (caregivers in case of children);
  7. 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.

Exclusion criteria

Exclusion Criteria:

  1. Known or suspected intolerance to anaesthesia;
  2. Bad general condition ( index >1);
  3. Presence of any skin cancers in the area(s) qualified for treatment;
  4. Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
  5. 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 [WOCBP]) UNLESS they are willing to use highly effective methods;
  6. Allergy, sensitivity or intolerance to study medication or other material required by study protocol (as per Investigator's brochure)
  7. to the local or systemic antibiotics and/or foreseen by the protocol;
  8. Contraindications to undergo extensive surgical procedures;
  9. Presence of i) systemic diseases, ii) 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;
  10. 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.
  11. 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.
Terms in these criteria, in plain language(8)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Excipients

The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
2 participants (actual)

Study arms

  • Experimental
    Treatment

    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.

    Drug: Transplantation

Interventions

  • DrugTransplantation

    Implantation of autologous cultured grafts containing genetically modified stem cells for restoration of functional skin on pre-selected areas

    Also known as: Engraftment

06

What researchers measure

Primary outcomes

  1. Re-epithelialization

    Re-epithelialization in absence of blisters in at least 50% of the transplanted area measured by the Investigator

    Time frame: 12 months

  2. Protein residual expression

    Protein residual expression resulting in 'Yes' or 'Partial' measured by Immunofluorescence

    Time frame: 12 months

  3. Expression of transgenic mRNA

    Expression of transgenic mRNA resulting in 'Yes' or 'Partial' measured by In situ hybridization

    Time frame: 12 months

  4. Hemidesmosomes presence

    Presence of hemidesmosomes measured by electron microscopy

    Time frame: 12 months

  5. Skin stability

    Negativity or positivity at the stripping test

    Time frame: 12 months

  6. 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

    Time frame: 12 months

Secondary outcomes

  1. Re-epithelialization by Independent Assessor

    % of re-epithelialization assessed by the Independent Assessor

    Time frame: 12 months

  2. 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

    Time frame: 12 months

  3. Treatment-emergent adverse events

    Number and % of treatment-emergent adverse events

    Time frame: 12 months

  4. Serious adverse events

    Number and % of serious adverse events

    Time frame: 12 months

  5. Adverse events of special interest

    Number and % of adverse events of special interest

    Time frame: 12 months

  6. Adverse drug reactions

    Number and % of adverse drug reactions

    Time frame: 12 months

07

Study locations

2 sites
  • Hopital Necker-Enfants Malades
    Paris, France
  • Struttura Complessa di Dermatologia Azienda Ospedaliero Universitaria Policlinico di Modena
    Modena, Italy
08

References and documents

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Jul 2022 to primary completion in Mar 2024, 19 months.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 1, 2021
First posted
Nov 8, 2021
StartActual
Jul 15, 2022
Primary completionActual
Mar 12, 2024
CompletionActual
Nov 22, 2024
Last update
Feb 19, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 19, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05111600
Lead sponsor
Holostem s.r.l.
Collaborators
IRCCS San Raffaele, University of Modena and Reggio Emilia
Responsible party
Sponsor
First posted
Nov 8, 2021
Start date
Jul 15, 2022
Primary completion
Mar 12, 2024
Completion
Nov 22, 2024
Last update
Feb 19, 2025

Study contacts

Cristina Magnoni, MD, Surgeon
principal investigator · Struttura Complessa di Dermatologia Azienda Ospedaliero Universitaria Policlinico di Modena

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.

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