E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neurogenic bladder secondary to spina bifida |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029279 |
E.1.2 | Term | Neurogenic bladder |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041524 |
E.1.2 | Term | Spina bifida |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to demonstrate that augmentation cystoplasty using an autologous neo-bladder construct will significantly increase bladder compliance in subjects with neurogenic bladder secondary to spina bifida (myelodysplasia) that is refractory to medical treatment.
Primary outcome measure • Percent change from baseline in bladder compliance as assessed by standardized urodynamic measurements at 12 months |
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E.2.2 | Secondary objectives of the trial |
Secondary Outcome Measures in the Primary Analysis Phase
Safety • Overall safety assessment Efficacy • Percent change from baseline in bladder capacity as assessed by standardized urodynamic measurements at 12 months • Percent change from baseline in bladder compliance and capacity as assessed by standardized urodynamic measurements at 6, 9, 36 and 60 months • End filling pressure at age-related nomogram-derived bladder capacity at baseline, 6, 9, 12, 30 and 60 months
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects between the ages of 3 and 21 years of age with myelodysplasia (spina bifida)
2. Willing and able to give signed informed consent, or have a legally authorized representative who is willing and able to give consent. Informed assent will be required for children < 18 years of age as appropriate or warranted.
3. Ability of subject and/or care provider to be successfully trained in clean intermittent catheterization and bladder cycling
4. Uilization of maximally-tolerated dose and regimen of medical therapy (e.g. anticholinergics) or failure to tolerate /contraindication to such agents
5. Medical need for bladder augmentation, as defined by the presence of: a. Decreased and inadequate bladder compliance with a bladder pressure ≥40 cmH20 at or below estimated bladder capacity for age, OR b. New-onset of upper urinary tract changes (hydronephrosis, vesicoureteral reflux) in the last 12 months
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E.4 | Principal exclusion criteria |
1. Female subjects who are pregnant, lactating (breast feeding) or planning a pregnancy during the course of the study, or who are of child bearing potential and not using a highly effective method of birth control (including sexual abstinence). A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or a vasectomised partner. Subjects must be willing to continue to use one of these methods throughout the duration of the study.
2. Recent (< 12 months) urological or intraperitoneal surgery or device implantation; recent (<6 month neurological surgery-brain or spine)
3. Any prior bladder augmentation procedure
4. Requirement of concomitant urological surgical procedures in addition to augmentation (e.g., ureteral reimplantation). Minor surgical correction for bladder neck incompetence (i.e., fascial sling) is permitted.
5. Known or suspected limitation to obtaining omentum for implantation procedure (e.g., extensive intraperitoneal adhesions)
6. Any contraindication to general anaesthesia
7. Any contraindication or known anaphylactic or severe systemic reaction to either human blood products or materials of bovine origin
8. Immunocompromised subjects or subjects receiving immunosuppressive agents (inhaled corticosteroids and chronic low-dose corticosteroids [≤0.25 mg/kg prednisone or equivalent per day] are permitted). Brief pulsed corticosteroids for intermittent symptoms (e.g., asthma) are permitted.
9. Known history of hypersensitivity to aminoglycosides or fluoroquinolones.
10. Use of any investigational product within 3 months
11. Prior participation in the study
12. Unwillingness, inability, or unlikely compliance with study related procedures
13. Any circumstance in which the investigator deems participation in the study is not in the subject’s best interest
14. Subjects with an ALT or AST value >3 times the upper limit of normal
15. Subjects with an albumin value <3.0 g/dL
16. Subjects with a history of an anaphylactic or a severe systemic reaction to the biodegradable polymers glycolic acid (PGA) and lactic-co-glycolic acid (PLGA)
17. Subjects with acute or chronic abdominal skin infections and/or acute or chronic inflammatory bowel disease
18. Subjects with uncontrolled diabetes, unstable cardiac and/or pulmonary disorders, or bleeding disorders
19. Subjects who have received Botulinum Toxin A injections into the bladder within the previous 12 months.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in bladder compliance as assessed by standardized urodynamic measurements at 12 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned months | 62 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 62 |