Clinical Trial to Assess the Safety and Efficacy of Investigational Product in Patients Due to Hypospadias Treatment Failure

NCT05093166 | Terminated Phase 1

• 1 other identifier: HTA-HUR-01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypospadias

Keywords

Hypospadias treatment failure; Urethral reconstruction; Cell therapy; Stem cells

Outcome Measures

Primary Outcomes (10)

• Number and percentage of patients experiencing AESI

  To demonstrate the safety of Holour in terms of AESI (persistent fever, infections)

  3 months after treatment

• Number and percentage of patients experiencing ADRs

  To demonstrate the safety of Holour in terms of ADRs

  3 months after treatment

• Number and percentage of patients experiencing SAEs

  To demonstrate the safety of Holour in terms of SAEs

  3 months after treatment

• Number and percentage of patients experiencing Serious ADRs

  To demonstrate the safety of Holour in terms of Serious ADRs

  3 months after treatment

• Number and percentage of patients experiencing AESI

  To demonstrate the safety of Holour in terms of AESI (persistent fever, infections)

  12 months after treatment

• Number and percentage of patients experiencing ADRs

  To demonstrate the safety of Holour in terms of AESI ADRs

  12 months after treatment

• Number and percentage of patients experiencing SAEs

  To demonstrate the safety of Holour in terms of SAEs

  12 months after treatment

• Number and percentage of patients experiencing Serious ADRs

  To demonstrate the safety of Holour in terms of Serious ADRs

  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.

  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.

  12 months after treatment

Secondary Outcomes (8)

• Number of patients with the treatment efficacy after Holour implantation and surgical reconstruction

  up to 1 year after implantation

• Evaluation of the percentage of re-epithelialization

  up to 1 year after implantation

• Evaluation of the clinical epithelial stability on the transplanted area by visual inspections

  up to 1 year after implantation

• Evaluation of scar retraction presence

  up to 1 year after implantation

• Evaluation of uroflowmetry rate

  From 3 to 12 months after the treatment

Study Arms (1)

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.

Drug: "Ex vivo" expanded autologous human oral epithelium containing stem cells

Interventions

"Ex vivo" expanded autologous human oral epithelium containing stem cells DRUG

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.

Urethral reduced functionality and/or lesions due to previous hypospadias treatment failure

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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):
• 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;

Sponsors & Collaborators

• Holostem s.r.l.: lead
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator
• University of Modena and Reggio Emilia: collaborator

Study Sites (1)

Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

MeSH Terms

Conditions

Hypospadias

Condition Hierarchy (Ancestors)

Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Penile Diseases; Genital Diseases, Male; Genital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Graziella Pellegrini, Professor

  Holostem s.r.l.

  STUDY DIRECTOR

• Gianantonio Manzoni, MD

  Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: October 26, 2021
• Study Start: November 26, 2021
• Primary Completion: December 12, 2022
• Study Completion: December 12, 2022
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)