E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of this study is to assess the safety and tolerability of ADSVF, as add-on treatment to endoscopic urethrotomy for recurrent bulbar urethral stenosis during the follow-up. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to obtain preliminary data on the efficacy of ADSVF injection as add-on treatment to endoscopic urethrotomy on: - validated symptoms scores (ICIQ male, USP and Personnal Global impression of Improvement (PGII scale), quantitative functional tests (uroflowmetry and post voiding residual assessment), recurrence rate (need for re intervention on the urethral stenosis) at 1, 3, 6, 9, 18 and 24 months, - imaging assessment of spongiofibrosis volume with Fat Sat sequences in an urethral MRI at 1 and 9 months. Relationship of efficacy and safety results with imaging, ADSVF composition and biological characteristics will be explored.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1) Signed informed consent (2) Male, aged from 18 to 85 years (3) Bulbar urethral stenosis ≤ 3 cm Although there is no concensus on a clear definition of what a significant bulbar UrS is to date, a significant Bulbar UrS will be defined as 3 dimension entity for the study: - A narrowing of urethra that does not accept a standard flexible fibroscope (CH16) to pass through - In a patient with bothersome voiding and/or storage symptoms or any complication (infection, retention) who is asking for a relief - Qmax ≤ 15 ml/s AND USP ICIQ male LUTS voiding dysfunction domain ≠ 0 (Zero)
(4) At least one urethral dilatation or urthrotomy for the bulbar stenosis in the past 24 months before diagnosis of stenosis (5) Ability to avoid corticoids or immunosuppressive drugs one month after treatment (6) Good general health status according to clinical history and a physical examination (7 BMI > 18 to insure adequate access to abdominal or other subcutaneous adipose tissue for adipose tissue harvesting
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E.4 | Principal exclusion criteria |
(1) Urethral stenosis of other location than bulbar (2) Urethral stenosis length > 3 cm (3) Urethral stenosis on reconstructed penis (transgender, post amputation) (4) Prior perineal or pelvic radiotherapy (5) Concurent urinary tract infection without treatment (6) Concurent perineal infection (7) Penile cancer < 5 years (8) Current or recent history of abnormal, severe, progressive, uncontrolled infectious, hepatic, haematological, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease (9) Congenital or acquired immunodeficiencies (10) Contraindication to the anaesthetic or surgical procedure (11) Corticoids or immunosuppressive drugs > 3 months (12) Any active viral infection among the following: HIV, HTLV I and II, VHB, VHC and Syphillis (13) Administrative restricted rights
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints will include the frequency and intensity of classic adverse events of urethrotomy: urethral bleeding, urinary infection, urethral pain (intensity and duration), and urethral perforation with fistula or perineal soft tissue infection. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1, 3, 6, 9, 18 and 24 months. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are listed below and will be assessed at baseline 1, 3, 6, 9, 18 and 24 months. - Symptoms and quality of life using validated scale and questionnaires: ICIQ male LUTS (International Consultation on incontinence Questionnaire), USP (Urinary Symptom Profile) questionnaires and a PGII (Personnal Global impression of Improvement) scale. - US examination: Uroflowmetry (Qmax in ml/s, voided volume in ml) and post voiding residual volume using ultrasound bladder scan. - Recurrence occurring between 3 months and 24 months after the ADSVF injection and defined as a urinary retention or a decrease in uroflowmetry and quality of life equal to baseline situation ± 20% in a patient asking for a relief after an initial period of improvement (compare to baseline values) - Volume of spongiofibrosis using MRI in Sagittal view in T1 Fat Sat after Gadolinium injection (reconstruction to evaluate total volume in mm3 of spongiofibrosis).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 3, 6, 9, 18 and 24 months, |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
a procedure of endoscopic urethrotomy (standard care) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |