HypospadiasPhase 1/2HOLOURNCT05093166
Clinical Trial to Assess the Safety and Efficacy of Investigational Product in Patients Due to Hypospadias Treatment Failure
A Phase 1/2 study testing "Ex vivo" expanded autologous human oral epithelium containing stem cells in people with Hypospadias, run by Holostem s.r.l. at 1 site in Italy.
Trial summary
The purpose of this trial is to assess the safety and efficacy of Holour in patients suffering from hypospadias treatment failure. Holour is intended for urethral replacement and is made from ex vivo expanded autologous oral mucosal cells including stem cells. Read more about this study
- Who is it for?
- Ages 5 to 17 years, men only
- Conditions the study is for
- Hypospadias
- What is being tested?
- "Ex vivo" expanded autologous human oral epithelium containing stem cells
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteItaly
- Study dates
- 26 Nov 2021to 12 Dec 2022
- 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 5 to 17 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Signed and dated informed consent prior to any study-related procedures (Caregivers); Patients whose parents/legal representatives have been thoroughly informed of the aim of the study procedures and provided signed and dated written informed consent;
- Male patients between 5 and 17 years old (less than 18 years old);
- Need for urethroplasty in failed hypospadias treatment;
- Hypospadias complications shown by clinical evaluation, uroflowmetry with post-micturition residual evaluation and/or retrograde urethrography and/or urethroscopy;
- Uroflowmetry rate: Uroflowmetry with a plateau-shaped curve and low qmax according to paediatric uroflow normograms;
- Absence of other contraindications to HOLOUR implantation based on investigator's judgement;
- 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 >2);
- Clinical and/or laboratory signs of acute systemic infections and/or severe inflammation at the time of screening. Patient can be re-screened after appropriate treatment;
- Severe systemic disease (i.e. uncompensated diabetes);
- Stenosis or retraction secondary to medical conditions other than hypospadias failure (i.e. radiotherapy, lichen sclerosis, etc…);
- Allergy, sensitivity or intolerance to drugs or excipients (hypersensitivity to any of the excipients listed in Investigator's brochure or in this protocol):
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- Transport medium (Dulbecco's Modified Eagles Medium supplemented with L-glutamine)
- Fibrin support;
- Contraindications to the post- treatment local or systemic antibiotics and/or corticosteroids;
- UTI or urine culture positive requiring a re-screening of patient;
- Contraindications to undergo extensive surgical procedures;
- Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell implantation based on investigator's judegment or other concomitant medical conditions affecting grafting procedure;
- Patients and parents/tutor 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 conventional investigational drug was received less than 1 months prior to screening visit;
- Patients who received surgical procedure within 6 months prior to screening visit;
- Anaesthesia or severe hypoesthesia of the area;
- Diagnosis of local or systemic neoplastic disease.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
Milan, 20122
About this study
Official title: Prospective, Open-label, Uncontrolled Pilot Clinical Trial to Assess the Safety and Efficacy of Autologous Cultured Oral Mucosa Grafts for Urethral Reconstruction in Patients Due to Hypospadias Treatment Failure
The purpose of this trial is to assess the safety and efficacy of Holour in patients suffering from hypospadias treatment failure. Holour is intended for urethral replacement and is made from ex vivo expanded autologous oral mucosal cells including stem cells.
Read the detailed description
Holour is a prospective, open-label, uncontrolled pilot clinical trial phase i/ii. The aim of this clinical trial is to perform a tissue engineering therapy to assess the safety (at 3 and 12 months) and efficacy (at 12 months) of the autologous treatment.
Patients will be screened according to the study inclusion and exclusion criteria and will be candidate for the treatment if all eligibility criteria are met. Up to 8 patients will be treated by means of autologous cultured oral mucosa grafts containing oral mucosa stem cells. Holour is produced by ex vivo expansion of cells obtained from oral mucosa biopsy collected from patient. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where the epithelial cells will be isolated, expanded and prepared as final graft to be implanted. Holour administration will be planned according to the procedures and the need of the patient.
The entire procedure envisages the following steps:
- Oral mucosa biopsy to manufacture autologous grafts of Holour.
- Penile urethroplasty in two stages:
- First stage: application of holour on the wound bed prepared according to standard surgery.
- Second stage: penis reconstruction according to standard surgical procedure. The surgical procedures may be followed by a post-implantation treatment (if necessary) with corticosteroids and antibiotics.
The treatment includes a single administration of Holour; in case of "failure" of the first procedure eligible patients can undergo to a second implantation.
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.
- Conditions
- Hypospadias
- Being tested
- "Ex vivo" expanded autologous human oral epithelium containing stem cells
- Keywords
- Hypospadias treatment failure, Urethral reconstruction, Cell therapy, Stem cells
- Medical subject headings
- Hypospadias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
"Ex vivo" expanded autologous human oral epithelium containing stem cellsDrug
The treatment includes a single administration of investigational product through a dedicated surgical procedure of penis wound bed preparation, epithelial surface adaption and product application followed by urethra tubularization and penis reconstruction.
| Study group | Role | What they receive |
|---|---|---|
| Urethral reduced functionality and/or lesions due to previous hypospadias treatment failure | Experimental | The first step consists in a small oral mucosa biopsy collection by surgeon under general anaesthesia. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where the epithelial cells will be isolated, expanded and prepared as final graft to be implanted.
The treatment for urethra reconstruction required a two stage urethroplasty:
1. First stage: application of Holour on the wound bed prepared according to standard surgery The penis will be immobilized for some days after this operation.
2. Second stage: surgical procedure for urethral tubularization and penile reconstruction according to standard surgical procedure.
The surgical procedures may be followed by a post-implantation treatment (if necessary) with corticosteroids and antibiotics. Receives: Drug: "Ex vivo" expanded autologous human oral epithelium containing stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and percentage of patients experiencing AESI
To demonstrate the safety of Holour in terms of AESI (persistent fever, infections)
Measured: 3 months after treatment
Number and percentage of patients experiencing ADRs
To demonstrate the safety of Holour in terms of ADRs
Measured: 3 months after treatment
Number and percentage of patients experiencing SAEs
To demonstrate the safety of Holour in terms of SAEs
Measured: 3 months after treatment
Number and percentage of patients experiencing Serious ADRs
To demonstrate the safety of Holour in terms of Serious ADRs
Measured: 3 months after treatment
Number and percentage of patients experiencing AESI
To demonstrate the safety of Holour in terms of AESI (persistent fever, infections)
Measured: 12 months after treatment
Number and percentage of patients experiencing ADRs
To demonstrate the safety of Holour in terms of AESI ADRs
Measured: 12 months after treatment
Number and percentage of patients experiencing SAEs
To demonstrate the safety of Holour in terms of SAEs
Measured: 12 months after treatment
Number and percentage of patients experiencing Serious ADRs
To demonstrate the safety of Holour in terms of Serious ADRs
Measured: 12 months after treatment
Number of patients with implantation success
Implantation success is defined on the basis of the degree of clinical (no lesions, no significant retractions) epithelial stability on the transplanted area. The degree of epithelial stability will be evaluated by visual inspection, cistouretrography, uretroscophy and checked for evaluating reepithelialization, erosions, infection, etc. and documented with photos with measures.
Measured: 12 months after treatment
percentage of patients with implantation success
Implantation success is defined on the basis of the degree of clinical (no lesions, no significant retractions) epithelial stability on the transplanted area. The degree of epithelial stability will be evaluated by visual inspection, cistouretrography, uretroscophy and checked for evaluating reepithelialization, erosions, infection, etc. and documented with photos with measures.
Measured: 12 months after treatment
Secondary outcomes (8)
Number of patients with the treatment efficacy after Holour implantation and surgical reconstruction
Regeneration of a clinically normal appearing urethra epithelium with absence of detectable erosions/retractions and Clinical functionality (uroflowmetry) after the second step (urethral reconstruction) of transplant.
Measured: up to 1 year after implantation
Evaluation of the percentage of re-epithelialization
Evaluation of the percentage of re-epithelialization
Measured: up to 1 year after implantation
Evaluation of the clinical epithelial stability on the transplanted area by visual inspections
Evaluation of the regeneration of a clinically normal appearing epithelium with absence of detectable erosions/retractions
Measured: up to 1 year after implantation
Evaluation of scar retraction presence
Evaluation of the penile retraction due to presence/absence of scars
Measured: up to 1 year after implantation
Evaluation of uroflowmetry rate
Evaluation of the change of uroflowmetry compared to the baseline value with change of the curve shape and significant increase of the qmax flow rate;
Measured: From 3 to 12 months after the treatment
Evaluation of the post-void residual volume through uroflowmetry
Evaluation of the change of the post-void residual compared to the baseline
Measured: From 3 to 12 months after the treatment
Evaluation of the presence and severity of surgical complications
Presence and severity of surgical complications using the Clavien Dindo scale with the classification into 5 grades (I, II, III, IV and V from no need for clinical intervention to the death of the patient)
Measured: up to 1 year after implantation
Evaluation of the adeverse events in terms of SAEs, AESI, ADR Serious ADRs,
Evaluation of the adeverse events in terms of SAEs, AESI, ADR Serious ADRs,
Measured: up to 1 year after implantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2021
- Study start26 Nov 2021
- Primary completion12 Dec 2022
- Study completion12 Dec 2022
Why it stopped: Due to the current re-organization at the Sponsor site
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypospadiasStudies 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Holostem s.r.l.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Modena and Reggio Emilia
- Responsible party
- Sponsor
- Investigators
- Graziella Pellegrini, Professor, Study director, Holostem s.r.l.Gianantonio Manzoni, MD, Principal investigator, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05093166
- Sponsor's protocol ID
- HTA-HUR-01
- Acronym
- HOLOUR
- Status last verified
- Nov 2024
- First submitted
- 3 Sep 2021
- Last updated
- 12 Nov 2024
- 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 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Open-label, Uncontrolled Pilot Clinical Trial to Assess the Safety and Efficacy of Autologous Cultured Oral Mucosa Grafts for Urethral Reconstruction in Patients Due to Hypospadias Treatment Failure
- ClinicalTrials.gov ID
- NCT05093166
- Acronym / sponsor ID
- HOLOUR / HTA-HUR-01
- Conditions
- Hypospadias
- Keywords
- Hypospadias treatment failure, Urethral reconstruction, Cell therapy, Stem cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the current re-organization at the Sponsor site
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Holostem s.r.l.Industry (pharma, biotech, devices)
- Collaborators
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Modena and Reggio Emilia
- Study start
- 26 Nov 2021 (actual)
- Primary completion
- 12 Dec 2022 (actual)
- Study completion
- 12 Dec 2022 (actual)
- First posted
- 26 Oct 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.
The purpose of this trial is to assess the safety and efficacy of Holour in patients suffering from hypospadias treatment failure. Holour is intended for urethral replacement and is made from ex vivo expanded autologous oral mucosal cells including stem cells.
Detailed description
Holour is a prospective, open-label, uncontrolled pilot clinical trial phase i/ii. The aim of this clinical trial is to perform a tissue engineering therapy to assess the safety (at 3 and 12 months) and efficacy (at 12 months) of the autologous treatment.
Patients will be screened according to the study inclusion and exclusion criteria and will be candidate for the treatment if all eligibility criteria are met. Up to 8 patients will be treated by means of autologous cultured oral mucosa grafts containing oral mucosa stem cells. Holour is produced by ex vivo expansion of cells obtained from oral mucosa biopsy collected from patient. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where the epithelial cells will be isolated, expanded and prepared as final graft to be implanted. Holour administration will be planned according to the procedures and the need of the patient.
The entire procedure envisages the following steps:
- Oral mucosa biopsy to manufacture autologous grafts of Holour.
- Penile urethroplasty in two stages:
- First stage: application of holour on the wound bed prepared according to standard surgery.
- Second stage: penis reconstruction according to standard surgical procedure. The surgical procedures may be followed by a post-implantation treatment (if necessary) with corticosteroids and antibiotics.
The treatment includes a single administration of Holour; in case of "failure" of the first procedure eligible patients can undergo to a second implantation.
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 |
|---|---|---|
| Urethral reduced functionality and/or lesions due to previous hypospadias treatment failure | Experimental | Drug: "Ex vivo" expanded autologous human oral epithelium containing stem cellsThe first step consists in a small oral mucosa biopsy collection by surgeon under general anaesthesia. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where the epithelial cells will be isolated, expanded and prepared as final graft to be implanted. The treatment for urethra reconstruction required a two stage urethroplasty: 1. First stage: application of Holour on the wound bed prepared according to standard surgery The penis will be immobilized for some days after this operation. 2. Second stage: surgical procedure for urethral tubularization and penile reconstruction according to standard surgical procedure. The surgical procedures may be followed by a post-implantation treatment (if necessary) with corticosteroids and antibiotics. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Signed and dated informed consent prior to any study-related procedures (Caregivers); Patients whose parents/legal representatives have been thoroughly informed of the aim of the study procedures and provided signed and dated written informed consent;
- Male patients between 5 and 17 years old (less than 18 years old);
- Need for urethroplasty in failed hypospadias treatment;
- Hypospadias complications shown by clinical evaluation, uroflowmetry with post-micturition residual evaluation and/or retrograde urethrography and/or urethroscopy;
- Uroflowmetry rate: Uroflowmetry with a plateau-shaped curve and low qmax according to paediatric uroflow normograms;
Key exclusion criteria (17 listed)
- Known or suspected intolerances against anaesthesia;
- Bad general condition (ECOG index >2);
- Clinical and/or laboratory signs of acute systemic infections and/or severe inflammation at the time of screening. Patient can be re-screened after appropriate treatment;
- Severe systemic disease (i.e. uncompensated diabetes);
- Stenosis or retraction secondary to medical conditions other than hypospadias failure (i.e. radiotherapy, lichen sclerosis, etc…);
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 |
|---|---|---|
| "Ex vivo" expanded autologous human oral epithelium containing stem cellsThe treatment includes a single administration of investigational product through a dedicated surgical procedure of penis wound bed preparation, epithelial surface adaption and product application followed by urethra tubularization and penis reconstruction. | Drug | Urethral reduced functionality and/or lesions due to previous hypospadias treatment failure |
Primary outcome
Number and percentage of patients experiencing AESI
Time frame: 3 months after treatment
To demonstrate the safety of Holour in terms of AESI (persistent fever, infections)
Number and percentage of patients experiencing ADRs
Time frame: 3 months after treatment
To demonstrate the safety of Holour in terms of ADRs
Number and percentage of patients experiencing SAEs
Time frame: 3 months after treatment
To demonstrate the safety of Holour in terms of SAEs
Number and percentage of patients experiencing Serious ADRs
Time frame: 3 months after treatment
To demonstrate the safety of Holour in terms of Serious ADRs
Number and percentage of patients experiencing AESI
Time frame: 12 months after treatment
To demonstrate the safety of Holour in terms of AESI (persistent fever, infections)
Number and percentage of patients experiencing ADRs
Time frame: 12 months after treatment
To demonstrate the safety of Holour in terms of AESI ADRs
Number and percentage of patients experiencing SAEs
Time frame: 12 months after treatment
To demonstrate the safety of Holour in terms of SAEs
Number and percentage of patients experiencing Serious ADRs
Time frame: 12 months after treatment
To demonstrate the safety of Holour in terms of Serious ADRs
Number of patients with implantation success
Time frame: 12 months after treatment
Implantation success is defined on the basis of the degree of clinical (no lesions, no significant retractions) epithelial stability on the transplanted area. The degree of epithelial stability will be evaluated by visual inspection, cistouretrography, uretroscophy and checked for evaluating reepithelialization, erosions, infection, etc. and documented with photos with measures.
percentage of patients with implantation success
Time frame: 12 months after treatment
Implantation success is defined on the basis of the degree of clinical (no lesions, no significant retractions) epithelial stability on the transplanted area. The degree of epithelial stability will be evaluated by visual inspection, cistouretrography, uretroscophy and checked for evaluating reepithelialization, erosions, infection, etc. and documented with photos with measures.
8 secondary outcomes
Number of patients with the treatment efficacy after Holour implantation and surgical reconstruction
Time frame: up to 1 year after implantation
Evaluation of the percentage of re-epithelialization
Time frame: up to 1 year after implantation
Evaluation of the clinical epithelial stability on the transplanted area by visual inspections
Time frame: up to 1 year after implantation
Evaluation of scar retraction presence
Time frame: up to 1 year after implantation
Evaluation of uroflowmetry rate
Time frame: From 3 to 12 months after the treatment
Evaluation of the post-void residual volume through uroflowmetry
Time frame: From 3 to 12 months after the treatment
Evaluation of the presence and severity of surgical complications
Time frame: up to 1 year after implantation
Evaluation of the adeverse events in terms of SAEs, AESI, ADR Serious ADRs,
Time frame: up to 1 year after implantation
Results and safety
The study was stopped early (reason given: Due to the current re-organization at the Sponsor site). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- 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.
Graziella Pellegrini, Professor study director
Holostem s.r.l.
Gianantonio Manzoni, MD principal investigator
Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
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 "Ex vivo" expanded autologous human oral epithelium containing stem cells in people with Hypospadias, run by Holostem s.r.l. at 1 site in Italy.
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 17 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 12 Nov 2024. 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 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 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: Due to the current re-organization at the Sponsor site). 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?
Number and percentage of patients experiencing AESI (time frame: 3 months after treatment). The study lists 10 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 12 Nov 2024.