E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stress urinary incontinence (SUI) in female patients with predominately intrinsic sphincter deficiency of moderate severity |
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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 | 10066218 |
E.1.2 | Term | Stress urinary incontinence |
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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 |
The objective of this study is to find the optimal cell count for functional regeneration of the urethral sphincter, including safety evaluation.
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E.2.2 | Secondary objectives of the trial |
Efficacy variables: • Change from baseline in the IEF score for comparison of each pair wise combination of treatment groups not considered in the primary analysis, • Change from screening in the short pad-test results, • Change from baseline in the I-QoL score, • Change from baseline in the Visual Analog Scale (VAS) score, • Frequency of responders regarding the IEF score; different definitions of response (reduction by 50% and 75%) will be used, • Amount of urinary volume lost during incontinence episodes, • Correlation between fluids taken and IEF score, • Investigator’s assessment by Clinical Global Impression (CGI) score.
Standard safety examinations like comparison of routine laboratory measures and frequency, type, intensity, and seriousness of AEs including Suspected Unexpected Serious Adverse Reactions (SUSARs) will be provided. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients of ≥ 18 years of age, • Age limit approved for Germany: 18 – 75 years, • Age limit approved for the Czech Republic: 18 – 65 years. 2. Graded as moderate SUI at screening visit, according to the classification based on the short-pad test of Hahn and Fall (1991): Grade 2 (2-10 mL leakage) or Grade 3 (11-50 mL leakage), 3. Diagnosed with SUI, predominantly intrinsic sphincter deficiency, confirmed by ambulatory urodynamic testing (filling cystometry) at screening. Patients will be included only in case of: • missing detrusor overactivity, i.e. involuntary detrusor contraction with a pressure <15 cm H2O, • a cystometric capacity >300 mL, • compliance of >25 mL/cm H2O, • post void residual urine <50 mL, • ability to void urine spontaneously. 4. The SUI diagnosis has to be based on the patient’s medical history (including anamnestic complaints of involuntary leakage on effort or exertion or on sneezing or coughing) and a positive cough test (fixed volume) at the screening visit, 5. History of inefficient, insufficient, and/or refused pelvic floor muscle training (PFMT), 6. Patients who have a negative urine test (dipstick) at visit 0, 7. Patients willing and able to comply with the study procedures, 8. Patients who are mentally competent and able to understand all study requirements, 9. Patients must agree to read and sign informed consent form prior to any study related procedures, 10. Female patients of childbearing potential willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence). |
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E.4 | Principal exclusion criteria |
1. Pelvic organ prolapse > Stage II (ICS-Classification: The most distal portion of the prolapse is more than 1 cm below the plane of the hymen, but protrudes no further than two centimeters less than the total vaginal length in cm) detected during the last 12 months prior to patient inclusion in the study [Ref a)1], 2. Patients who have a medical history of uncontrolled overactive bladder (OAB), or urinary incontinence other than SUI (including anamnestic complaints on involuntary urine leakage accompanied by or immediately preceded by urgency, not stress induced), 3. Patients who have undergone a surgery in pelvis minor due to cancer, 4. Patients who have undergone any surgery for SUI, i.e. midurethral slings, bulking agents, 5. Patients diagnosed with human immunodeficiency virus (HIV), acute or chronic viral hepatitis HCV, acute viral hepatitis HBV, and/or active Syphilis, 6. Patients diagnosed with any kind of skeletal muscle disease, 7. Patients who, according to the clinical judgment of the investigator, are not suitable for this study, 8. Patients who are currently participating or have participated in another clinical trial (testing medical device or drug) within 30 days prior to the study begin or have previously participated in the current clinical study, 9. Patients who are pregnant, lactating, or intending pregnancy in the near future, and those of childbearing potential who are not willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence), 10. Patients with uncontrolled diabetes mellitus type I or II, or suffering from diabetic peripheral neuropathic pain, 11. Patients with compromised immune systems, 12. Patients complaining about symptoms of acute cystitis or urethritis at visit 0, 13. Patients who had previously undergone radiation of the pelvis, 14. Patients with coagulopathy and/or currently being under treatment with anticoagulant drugs. However, if the anticoagulant therapy may be changed to heparin treatment prior to the therapy (only valid for patients in cell implantation groups), the patients can be included into the study, 15. Patients with chronic pelvic pain or complaining about pelvic pain syndrome and/or dyspareunia, 16. Patients suffering from major depressive disorders, and/or generalized anxiety disorders, 17. Patients treated with monoamine oxidase inhibitors (MAOIs) and/or sedatives, serotonergic drugs (including triptans), alpha(1)-adrenoreceptor antagonists, 18. Patients with a history of: duloxetine treatment within a period of 6 months prior to patient inclusion, liver disease resulting in hepatic impairment, uncontrolled hypertension, severe renal impairment, hypersensitivity to hydrochloride, and/or treatment with CYP1A2 inhibitors as fluvoxamine, ciprofloxacin, or enoxacine, and/or CYP3A4 inducers such as St. John’s wort, 19. Patients with uncontrolled narrow-angle glaucoma, 20. Patients with severe myocardial disorders or irregular pulse, and those with an artificial pacemaker, 21. Patients with implantations of metal components in the electrical stimulation treatment area, 22. Patients dependent from the sponsor, CRO, or the investigator (e.g. employees, relatives, etc.), 23. Patients with malignant disease not in remission for five years or more, 24. Patients with any persistent chronic bacterial infections as well as local infections, 25. Patients with known hypersensitivity to any component of the product (autologous cells, ringer’s lactate, human serum albumin, DMSO, bovine proteins, fibroblast growth factor). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline (visit -5) of the Incontinence Episode Frequency (IEF) score. The IEF is calculated as number of incontinence episodes that occurred during 7 days receding a visit. |
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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 | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 | Information not present in EudraCT |
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 | 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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last visit of the last patient |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |