E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fecal incontinence in female and male patients. |
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E.1.1.1 | Medical condition in easily understood language |
Fecal incontinence is the involuntary loss of flatus and/or solid or liquid stool or the inability to control the discharge of fecal matter through the anus. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016296 |
E.1.2 | Term | Fecal incontinence |
E.1.2 | System Organ Class | 100000004856 |
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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 external anal sphincter. |
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E.2.2 | Secondary objectives of the trial |
Efficacy variables:
-Changes in frequency of incontinence episodes until Day 89 compared to the baseline
-Change in the Wexner score at day 90 and day 180 compared to baseline
-Change in the Visual Analogue Scale at day 90 and day 180 compared to baseline
-Frequency of response measured as a reduction of the frequency of incontinence episodes by more than 20 %, 50%, 75% and 90%, under treatment compared to the baseline
-Frequency of patients in remission
-Changes in the anorectal manometry data at day 180 compared to baseline
-Patient’s assessment based on the QoL questionnaire score
-Investigator’s assessment by the CGI score
-Change in the volume or thickness of external anal sphincter assessed by 3D sonography
-Examinations based on the incontinence diary records
-Pharmacoeconomic evaluation
Safety variables:
-Physical examination
-Vital signs
-Standard hematology, blood chemistry, and urinalysis
-Pregnancy test
-Concomitant medication
-AEs and SAEs |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients of > or = 18 years of age,
2. Patients suffering from FI for more than 6 months, which is confirmed at screening by relevant medical history and anorectal examination,
3. Patients with Wexner score >9 and with at least 3 episodes of FI per week as measured in the bowel diary prior to Visit -1,
4. Patients with no indications against a surgery under anesthesia,
5. Patients willing and able to comply with the study procedures,
6. Patients who are mentally competent and able to understand all study requirements,
7. Patients must agree to read and sign the Informed Consent (IC) form prior to any study-related procedures,
8. Female patients of childbearing potential willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence).
Interim Inclusion Criterion:
Patients with a minimum of 3 non-gaseous incontinence episodes per week measured using the diary during the 2 weeks prior to visit -1 (day -70) (diary distributed at screening visit) |
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E.4 | Principal exclusion criteria |
1. Patients with pathological findings considered clinically relevant by the Investigator (excluding sphincter damage) based on rectoscopy and ultrasound at the screening visit (e.g. grade I haemorrhoids would be considered acceptable),
2. Patients who have undergone any anorectal surgery within the last 6 months prior to screening visit,
3. Patients with more than one overlap repair surgery,
4. Patients with more than 2 anorectal surgical procedures (in total) e.g.
- primary repair after delivery and one overlap repair later-on,
- in- and explantation of a permanent neurostimulation system,
5. Patients with overlap repair and associated early atrophy of external anal sphincter,
6. Patients with a history of artificial anal sphincter surgery,
7. Patients with trans- or perianal injection of any bulking products,
8. Patients with a malignant disease not in remission for 5 years or more,
9. Patients who had undergone radiation therapy,
10. Patients who had undergone chemotherapy within last 5 years prior to study enrolment,
11. Patients with chemotherapy related neuropathy of the bowel and pelvis,
12. Patients with compromised immune system and/or rheumatic disease,
13. Patients under immunosuppressive therapy,
14. Patients with a diagnosis of chronic inflammatory bowel disease,
15. Patients with current and/or recurrent anal fistula disease,
16. Patients with chronic diarrhea,
17. Patients suffering from a disease which has not been
resolved within a timeframe prior to screening as follows:
fever and/or diarrhea of unknown reasons (4 weeks), HAV
(4 months), toxoplasmosis (6 months), osteomyelitis, Qfever, rheumatic fever, tuberculosis, or Salmonella infections (2 years), and malaria (4 years).
18. Patients who, according to the clinical judgment of the investigator, are not suitable for inclusion due to acute anal sphincter injury including obstetric and other trauma, acute disc prolapse, or neurological diseases (spinal cord injury, multiple sclerosis, Parkinson’s disease, stroke, etc.),
19. Patients with uncontrolled diabetes mellitus type I or II, or suffering from diabetic peripheral neuropathic pain,
20. Patients diagnosed with human immunodeficiency virus (HIV), acute or chronic viral hepatitis HCV, acute or chronic viral hepatitis HBV, active Syphilis, HTLV (tested upon risk assessment by investigator),
21. Patients diagnosed with any kind of skeletal muscle disease and/or neuronal disorders,
22. Patients with known hypersensitivity to any component of the product (autologous cells, ringer’s lactate, human serum albumin, DMSO, bovine proteins, fibroblast growth factor [FGF]),
23. Patients with clinically relevant abnormal laboratory values, any persistent chronic bacterial infections as well as local infections as indicated by a high level of the C-reactive protein (CRP) of >35 mg/l and confirmed by bacteriological analysis, or with any bleeding disorder,
24. Patients who, according to the clinical judgment of the investigator, are not suitable for this study,
25. Patients who are currently participating or have participated in another clinical trial (testing a medical device or drug) within 30 days prior to the study begin or have previously participated in the current clinical study,
26. 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) or who have a positive pregnancy test (only to be performed in women of childbearing potential),
27. Patients dependent from the sponsor, CRO, or the investigator (e.g. employees, relatives, etc.).
28. Patients deprived of their liberty by a judicial or administrative decision, patients admitted to a hospital, social institution or who are under a measure of legal protection, patients hospitalized without consent or who are in an emergency situation.
29. Patients with severe myocardial disorders, irregular pulse or a pacemaker,
30. Patients with implantations of metal components in the electrical stimulation treatment area,
31. Patients with chronic constipation and/or overflow incontinence.
Interim Exclusion Criterion:
Patients with persistent bacterial infections confirmed by clinical signs and positive results in bacteriological testing at visit-1 (Salmonella (Typhus), F. tularensis (Tularaemia), M. leprae (Leprosy), Brucella, Rickettsia). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the current study is the changes in frequency of incontinence episodes at V4 (from Day 152 until Day 179) compared to baseline V0(day -28 to day -1), in each treatment group. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- 2 weeks before the biopsy (day -84 to day -70),
- 4 weeks before the implantation (day -28 to day -1),
- 4 weeks after the implantation (day 1 to 29),
- and 4 weeks before V3 (day 62 to 90) and V4 (day 152 to 179)
|
|
E.5.2 | Secondary end point(s) |
Efficacy variables:
-Changes in frequency of incontinence episodes until Day 89 compared to the baseline
-Change in the Wexner score at day 90 and day 180 compared to baseline
-Change in the Visual Analogue Scale at day 90 and day 180 compared to baseline
-Frequency of response measured as a reduction of the frequency of incontinence episodes by more than 20 %, 50%, 75% and 90%, under treatment compared to the baseline
-Frequency of patients in remission
-Changes in the anorectal manometry data at day 180 compared to baseline
-Patient’s assessment based on the QoL questionnaire score
-Investigator’s assessment by the CGI score
-Change in the volume or thickness of external anal sphincter assessed by 3D sonography
-Examinations based on the incontinence diary records
-Pharmacoeconomic evaluation
Safety variables:
-Physical examination
-Vital signs
-Standard hematology, blood chemistry, and urinalysis
-Pregnancy test
-Concomitant medication
-AEs and SAEs |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening (visit -2), visit -1, visit 0, visit 1, visit 2, visit 3 and visit 4 |
|
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 | Yes |
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | 15 |
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 | 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
|
Last visit of the last patient. |
|
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 | 21 |
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 | 21 |
E.8.9.2 | In all countries concerned by the trial days | 0 |