Urethral reconstruction in patients due to hypospadias treatment failure.
Conditions
Interventions
Product Name: Ex vivo expanded autologous human epithelial cells containing oral mucosa highly proliferative cells
Product Code: [Holour]
Pharmaceutical Form: Implant
Current Sponsor code: -
Concentra
Sponsors
HOLOSTEM TERAPIE AVANZATE S.R.L.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Subjects must meet all the following inclusion criteria to be eligible for enrolment into the study: 1. 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 2. Male patients between 5 and 17 years old (less than 18 years old); 3. Need for urethroplasty in failed hypospadias treatment; 4. Hypospadias complications shown by clinical evaluation, uroflowmetry with post-micturition residual evaluation and/or retrograde urethrography and/or urethroscopy; 5. Uroflowmetry rate: Uroflowmetry with a plateau-shaped curve and low qmax according to paediatric uroflow nomograms; 6. Absence of other contraindications to HOLOUR implantation based on investigator's judgment; 7. A cooperative attitude to follow up the study procedures. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a subject from study enrolment: 1. Known or suspected intolerances against anaesthesia; 2. Bad general condition (ECOG index >2); 3. 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; 4. Severe systemic disease (i.e. uncompensated diabetes); 5. Stenosis or retraction secondary to medical conditions other than hypospadias failure (i.e. radiotherapy, lichen sclerosis, etc…); 6. 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. 7. Contraindications to the post- treatment local or systemic antibiotics and/or corticosteroids; 8. UTI or urinoculture positive require a re-screening of patient; 9. Contraindications to undergo extensive surgical procedures; 10. Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell implantation based upon investigator’s judgment or other concomitant medical conditions affecting grafting procedure; 11. 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; 12. Participation in another clinical trial where conventional investigational drug was received less than 1 months prior to screening visit; 13. Patients who received surgical procedure within 6 months prior to screening visit; 14. Anaesthesia or severe hypoesthesia of the area; 15. Diagnosis of local or systemic neoplastic disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Safety Objective: To demonstrate the safety of HOLOUR in terms of AESI (persisten fever, infections), ADRs, SAEs, Serious ADRs, at 3 months and one year after the treatment for urethral reconstruction in patients suffering from urethral reduced functionality due to hypospadias treatment failure. Primary Efficacy Objective: To evaluate the clinical success of the implantation of HOLOUR at one year after the treatment. ;Secondary Objective: Secondary Objectives: - To evaluate the efficacy of the treatment with HOLOUR and reconstruction - To evaluate the percentage of re-epithelialization; - To evaluate the clinical epithelial stability on the transplanted area; - To evaluate the presence of scar retraction; - To evaluate the uroflowmetry rate; - To evaluate the postvoid residual; - To evaluate the safety using the Clavien Dindo score for surgical complications; - To evaluate the safety at any time after the treatment. ;Primary end point(s): Safety profile of the treatment with HOLOUR at 3 and 12 months after application (primary safety endpoint) will be described separately by age and summarized. AESIs, AEs, TEAEs and ADRs: •AEs will be coded by System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA). •Incidence of AEs, AESIs, serious AEs, ADRs and serious, ADRs will be summarized both in terms of frequency of patients with at least one event and in term of frequency of events. •Persistent fever and infections will be notified as Adverse Events of Special Interest. The number and percentage of AESI (judged as related or unrelated) will be presented. •In addition, ADRs will be also stratified based on their relationship to the following: oBiopsy; oImplantation of HOLOUR; oSurgical reconstruction of penis; oPost-implantation pharmacological treatment with systemic and topical corticosteroids and antibiotics; oCell-based product (HOLOUR). Vital signs and laboratory parameters •Vital signs ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NA;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Italy
Contacts
Public ContactFania Ferrari
Holostem Terapie Avanzate S.r.l.
Outcome results
None listed