Fecal incontinence in female and male patients with external anal sphincter weakness or sphincter damage. MedDRA version: 20.0 Level: LLT Classification code 10016296 Term: Fecal incontinence System Organ Class: 100000167639
Conditions
Interventions
Product Name: autologous Skeletal Muscle Derived Cells
Product Code: aSMDC
Pharmaceutical Form: Suspension for injection
Current Sponsor code: aSMDC
Other descriptive name: autologous Skeletal Muscle
Sponsors
Innovacell Biotechnologie AG
Eligibility
Sex/Gender
All
Inclusion criteria
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, 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 incontinence episodes per week measured at visit -1 (diary distributed at screening visit) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 227 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Patients with pathological findings (excluding sphincter damage) based on rectoscopy and ultrasound at the screening visit, 2. Patients who have undergone any anorectal surgery within the last 6 months prior to screening visit, 3. Patients with maximal one overlap repair in total, 4. Patients with more than 2 anorectal surgical procedures, (but maximal one overlap repair 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, 11. Patients with compromised immune system and/or rheumatic disease, 12. Patients under immunosuppressive therapy, 13. Patients with a diagnosis of chronic inflammatory bowel disease, 14. Patients with recurrent anal fistula disease, 15. Patients with chronic diarrhea, 16. 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). 17. 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.), 18. Patients with uncontrolled diabetes mellitus type I or II, or suffering from diabetic peripheral neuropathic pain, 19. 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), 20. Patients diagnosed with any kind of skeletal muscle disease and/or neuronal disorders, 21. 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]), 22. 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, 23. Patients who, according to the clinical judgment of the investigator, are not suitable for this study, 24. 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, 25. 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), 26. Patients dependent from the sponsor, CRO, or the investigator (e.g. employees, relatives, etc.). 27. Patients deprived of their lib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to find the optimal cell count for functional regeneration of the external anal sphincter.;Secondary Objective: Efficacy variables: -Changes in frequency of incontinence episodes until Day 90 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;Primary end point(s): The primary endpoint of the current study is the frequency of incontinence episodes occurred under treatment (from baseline until Day 180) compared to the baseline period (day -28 to day 0), in each treatment group.;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 0), - 4 weeks after the implantation (day 1 to 29), - and 4 weeks before V3 (day 62 to 90) and V4 (day 152 to 180) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy variables: -Changes in frequency of incontinence episodes until Day 90 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;Timepoint(s) of evaluation of this end point: Screening (visit -2), visit -1, visit 0, visit 1, visit 2, visit 3 and visit 4 | — |
Countries
Austria, Bulgaria, Czech Republic, Germany, Slovenia, Sweden, United Kingdom
Outcome results
None listed