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 |
Scarred narrowing of urethra |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 26.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046466 |
E.1.2 | Term | Urethral stricture |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 |
To compare tissue-engineered oral mucosa graft (MukoCell®) urethroplasty vs. native oral mucosa graft urethroplasty with respect to the 12-month recurrence rate (treatment failure rate) and long-term complication rate at the donor site |
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E.2.2 | Secondary objectives of the trial |
• To demonstrate the superiority of oral mucosal cell harvesting for TEOMG (MukoCell®) urethroplasty vs. native OMG urethroplasty with respect to short-term and mid-term complications at the donor site • To compare TEOMG (MukoCell®) urethroplasty vs. native OMG urethroplasty with respect to the 24-month recurrence rate (treatment failure rate) und long-term complication rate at the donor site • To evaluate safety and tolerability of TEOMG (MukoCell®) urethroplasty vs. native OMG urethroplasty.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed declaration of consent and data protection declaration obtained prior to any trial-specific procedures 2. Male patient aged ≥18 and ≤75 years 3. Urethral stricture fulfilling the following criteria: - Medical need for urethroplasty - Located pre-dominantly bulbar - No more than 3 previous urethrotomies
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E.4 | Principal exclusion criteria |
1. Any urethroplasty in the past 2. Presence of solely penile stricture 3. Penile /urethral abnormality (e.g. hypospadia, penile curvature, etc.) interfering with study related assessments 4. Lichen sclerosis 5 Previous radiation therapy or laser treatment of the urethral region 6. Acute or chronic urethritis, presence of balanitis 7. Acute or chronic infections in the oral cavity 8. Presence of urologic disease(s) interfering with urination 9. Concomitant therapy with medications that may lead to urinary retention (e.g. anticholinergics etc.) 10. Severe liver or kidney disease 11. Severe somatopathic, neurological and /or psychiatric disease(s) 12. Malignant growth (concurrent or previous cancer with a relapse-free and treatment-free interval of less than 5 years before the Screening visit)
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E.5 End points |
E.5.1 | Primary end point(s) |
Recurrence rate (treatment failure rate) up to Visit 8 (12 months [±2 weeks] after urethroplasty): The primary endpoint of the clinical trial is the recurrence rate (treatment failure rate) up to Visit 8, defined as the percentage of patients with a need for an intervention due to a medically relevant restenosis of urethra at the operated site diagnosed up to 12 months [±2 weeks] after urethroplasty. An intervention is defined as another urethroplasty or urethrotomy in the area of the initial urethroplasty conducted at the beginning of this clinical trial. Note: An intervention due to an anastomosis stricture is not counted as an intervention for the primary endpoint.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months after urethroplasty |
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E.5.2 | Secondary end point(s) |
1. Short-term donor site complication rate The calculation includes all patients with at least one solicited adverse reaction (reaction to harvesting of oral mucosa) at the donor site of moderate or severe intensity (rating scores 2 or 3) (i.e. donor site complications with onset ≤4 days after harvesting of oral mucosal cells /native OMG). 2. Mid-term donor site complication rate The calculation includes all patients with at least one solicited adverse reaction (reaction to harvesting of oral mucosa) at the donor site of moderate or severe intensity (rating scores 2 or 3) newly reported or ongoing defined as donor site complications occurring >4 days to <30 days after harvesting of oral mucosal cells /native OMG. 3. Long-term donor site complication rate The calculation includes all patients with at least one solicited adverse reaction (reaction to harvesting of oral mucosa) at the donor site of moderate or severe intensity (rating scores 2 or 3) newly reported or ongoing defined as donor site complications occurring ≥30 days to ≤24 months [±2 weeks depending on Visit 10] after harvesting of oral mucosal cells /native OMG). 4. Recurrence rate (treatment failure rate) up to Visit 10 (24 months [±2 weeks] after urethroplasty) 5. Change in mean uroflowmetry peak flow rates from baseline to 1 month after urethroplasty (Visit 1 vs. Visit 6) 6. Change in mean QoL-US score from baseline to 1, 6, 12, and 24 month(s) after urethroplasty (Visit 1 vs. Visits 6, 7, 8, and 10, respectively) 7. Change in mean QoL-DSS score from baseline to 1, 6, 12, and 24 month(s) after urethroplasty (Visit 1 vs. Visits 6, 7, 8, and 10, respectively)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Ad 1: 4 days after harvesting of oral mucosal cells / native OMG Ad 2: 30 days after harvesting of oral mucosal cells / native OMG Ad 3: 24 months after harvesting of oral mucosal cells / native OMG Ad 4: 24 months after urethroplasty Ad 5: 1 month after urethroplasty Ad 6: 1, 6, 12 and 24 months after urethroplasty Ad 7: 1, 6, 12 and 24 months after urethroplasty |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
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 |
conventional urethroplasty with oral mucosal graft |
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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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |