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    Clinical Trial Results:
    Skeletal muscle-derived cell implantation for the treatment of fecal incontinence: a multicenter, randomized, double-blind, placebocontrolled, parallel-group, dose-finding clinical study.

    Summary
    EudraCT number
    		 2010-021463-32
    Trial protocol
    		 AT   DE   SE   CZ   GB   SI   BG  
    Global end of trial date
    19 Oct 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Sep 2021
    First version publication date
    11 Sep 2021
    Other versions
    Summary report(s)
    		 Synopsis STEFFI

    Trial information

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    Trial identification
    Sponsor protocol code
    IC-01-02-02-007
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Innovacell Biotechnologie AG
    Sponsor organisation address
    Mitterweg 24, Innsbruck, Austria, 6020
    Public contact
    Clinical Department Innovacell, Innovacell AG, office@innovacell.com
    Scientific contact
    Clinical Department Innovacell, Innovacell AG, office@innovacell.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Mar 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 May 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Oct 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    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.
    Protection of trial subjects
    This study was conducted in full accordance with the International Conference of Harmonisation Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Nov 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Slovenia: 16
    Country: Number of subjects enrolled
    Sweden: 47
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    Austria: 80
    Country: Number of subjects enrolled
    Bulgaria: 20
    Country: Number of subjects enrolled
    Czechia: 36
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 78
    Country: Number of subjects enrolled
    Switzerland: 4
    Worldwide total number of subjects
    288
    EEA total number of subjects
    279
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    149
    From 65 to 84 years
    137
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 Recruitment of patients per site was not limited and was competitive across countries (9) and sites (15) . Study recruitment started in November 2013 and was planned to last 4 months, actual recruitment period was 19 months. Supportive documents (poster, leaflet and newspaper publications) were developed to boost patient recruitment.

    Pre-assignment
    Screening details
    		 Patients were to be randomized in a double-blind manner in a ratio of 1:1:1 to one of the 3 treatment groups. 288 patients were screened and 251 patients were randomized. 237 patients were finally considered as ITT population.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Carer, Assessor, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LCC group
    Arm description
    		 Low cell count, 5 ± 1 x 10e6 autologous skeletal muscle derived cells were injected into the external anal sphincter of the patients.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Autologous skeletal muscle-derived cells
    Investigational medicinal product code
    Other name
    ICEF15
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Injection , Intramuscular use
    Dosage and administration details
    The IMP ( 5 ± 1 x 10e6 cells) is stored and transported in 3 x 1 mL cell transportation medium. Each dose of IMP is filled in 3 cryovials. Prior to implantation, IMP is prepared and thawed by addition of 3 x 1 mL Ringer’s lactate solution. Total volume of IMP injected for implantation is 6 mL. The IMP or placebo were injected (single administration) at Day 0 (Visit 0, V0) into the external anal sphincter of each patient using a standardized, ultrasound-guided injection tool under analgo sedation (or general anaesthesia, if preferred).

    Arm title
    		 HCC group
    Arm description
    		 High cell count, 50 ± 10 x 10e6 autologous skeletal muscle cells were injected into the external anal sphincter of the patients.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Autologous skeletal muscle-derived cells
    Investigational medicinal product code
    Other name
    ICEF15
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Injection , Intramuscular use
    Dosage and administration details
    The IMP (50±10x10e6 aSDMC) is stored and transported in 3 x 1 mL cell transportation medium. Each dose of IMP is filled in 3 cryovials. Prior to implantation, IMP is prepared and thawed by addition of 3 x 1 mL Ringer’s lactate solution. Total volume of IMP injected for implantation is 6 mL. The IMP or placebo were injected (single administration) at Day 0 (Visit 0, V0) into the external anal sphincter of each patient using a standardized, ultrasound-guided injection tool under analgo sedation (or general anaesthesia, if preferred).

    Arm title
    		 Placebo
    Arm description
    		 Placebo, injection of cell-free suspension into to external anal sphincter of the patient.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Injection , Intramuscular use
    Dosage and administration details
    The placebo is stored and transported in 3 x 1 mL cell transportation medium with no cells present. Each dose of IMP is filled in 3 cryovials. Prior to implantation, IMP is prepared and thawed by addition of 3 x 1 mL Ringer’s lactate solution. Total volume of IMP injected for implantation is 6 mL. The placebo were injected (single administration) at Day 0 (Visit 0, V0) into the external anal sphincter of each patient using a standardized, ultrasound-guided injection tool under analgo sedation (or general anaesthesia, if preferred).

    Number of subjects in period 1 [1]
    		LCC group HCC group Placebo
    Started
    86
    81
    84
    Completed
    83
    75
    79
    Not completed
    3
    6
    5
         Not exposed to cell implantation
    1
    -
    -
         Cell implantation not successful
    1
    3
    2
         Patient not exposed to cell implantation
    -
    3
    3
         No post baseline assessment available
    1
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: From the overall 288 patients screened only 251 were randomized to the study treatment. Finally 237 were considered as ITT population which includes all randomized patients for whom cell implantation was performed, and for whom baseline and at least one post-baseline evaluation of frequency per 7 days of incontinence episodes are available

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    LCC group
    Reporting group description
    		 Low cell count, 5 ± 1 x 10e6 autologous skeletal muscle derived cells were injected into the external anal sphincter of the patients.

    Reporting group title
    HCC group
    Reporting group description
    		 High cell count, 50 ± 10 x 10e6 autologous skeletal muscle cells were injected into the external anal sphincter of the patients.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo, injection of cell-free suspension into to external anal sphincter of the patient.

    Reporting group values
    		 LCC group HCC group Placebo Total
    Number of subjects
    		 86 81 84 251
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 59.6 ( 13.2 ) 61.4 ( 13.7 ) 59.4 ( 14.8 ) -
    Gender categorical
    Units: Subjects
        Female
    		 78 75 78 231
        Male
    		 8 6 6 20

    End points

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    End points reporting groups
    Reporting group title
    LCC group
    Reporting group description
    		 Low cell count, 5 ± 1 x 10e6 autologous skeletal muscle derived cells were injected into the external anal sphincter of the patients.

    Reporting group title
    HCC group
    Reporting group description
    		 High cell count, 50 ± 10 x 10e6 autologous skeletal muscle cells were injected into the external anal sphincter of the patients.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo, injection of cell-free suspension into to external anal sphincter of the patient.

    Primary: Absolute change IEF 6 month

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    End point title
    		 Absolute change IEF 6 month
    End point description
    The frequency of incontinence episodes were documented by a bowel diary that was completed by the patient. In this study, the frequency of incontinence episodes was calculated as the number of incontinence episodes over a period of 4 weeks.
    End point type
    Primary
    End point timeframe
    Change in frequency episodes at Visit 4 (from day 152 until day 179) compared to baseline Vo (day -28 to day -1), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: IEF change
        arithmetic mean (standard deviation)
    -4.3 ( 8.2 )
    -4.8 ( 6.8 )
    -3.2 ( 5.2 )
    Statistical analysis title
    		 LCC versus placebo
    Statistical analysis description
    The difference in the change of IE frequency per 7 days from baseline to V4 between treatment groups was investigated within a hierarchical test procedure using a one-sided Wilcoxon rank-sum test (SAS® PROC NPAR1WAY) with an alpha-level of 2.5% for each step.
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1116 [1]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Mean difference (net)
    Confidence interval
    Variability estimate
    Standard deviation
    Notes
    [1] - Threshold for significance at 0.025 level.
    Statistical analysis title
    		 HCC versus placebo
    Statistical analysis description
    The difference in the change of IE frequency per 7 days from baseline to V4 between treatment groups was investigated within a hierarchical test procedure using a one-sided Wilcoxon rank-sum test (SAS® PROC NPAR1WAY) with an alpha-level of 2.5% for each step.
    Comparison groups
    Placebo v HCC group
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0175 [2]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Mean difference (net)
    Confidence interval
    Variability estimate
    Standard deviation
    Notes
    [2] - Threshold for significance at 0.025

    Secondary: Absolute change IEF 1 month

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    End point title
    		 Absolute change IEF 1 month
    End point description
    The frequency of incontinence episodes were documented by a bowel diary that was completed by the patient. In this study, the frequency of incontinence episodes was calculated as the number of incontinence episodes over a period of 4 weeks.
    End point type
    Secondary
    End point timeframe
    Change in frequency of incontinence episodes (from day 1 to day 28) compared to the baseline period (day -28 to day -1), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: Absolute IEF change
        arithmetic mean (standard deviation)
    -3.4 ( 6 )
    -3.8 ( 6.9 )
    -1.9 ( 3.8 )
    No statistical analyses for this end point

    Secondary: Absolute change IEF 3 month

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    End point title
    		 Absolute change IEF 3 month
    End point description
    The frequency of incontinence episodes were documented by a bowel diary that was completed by the patient. In this study, the frequency of incontinence episodes was calculated as the number of incontinence episodes over a period of 4 weeks.
    End point type
    Secondary
    End point timeframe
    Change in frequency of incontinence episodes (from day 62 until day 89) compared to the baseline period (day -28 to day -1), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: Absolute change IEF
        arithmetic mean (standard deviation)
    -4.3 ( 7.3 )
    -4.5 ( 6.9 )
    -2.7 ( 4.8 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.271 [3]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [3] - Alpha level 5%
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.065 [4]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [4] - Alpha level 5%

    Secondary: Absolute change IEF 12 months

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    End point title
    		 Absolute change IEF 12 months
    End point description
    The frequency of incontinence episodes were documented by a bowel diary that was completed by the patient. In this study, the frequency of incontinence episodes was calculated as the number of incontinence episodes over a period of 4 weeks.
    End point type
    Secondary
    End point timeframe
    Change in frequency of incontinence episodes (from day 332 to day 359) compared to the baseline period (day -28 to day -1), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: Absolute IEF change
        arithmetic mean (standard deviation)
    -3.8 ( 6.6 )
    -5.5 ( 10.9 )
    -2.6 ( 5.1 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.459 [5]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [5] - Alpha level 5%
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.203
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Absolute change in Wexner Score 3 months

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    End point title
    		 Absolute change in Wexner Score 3 months
    End point description
    Symptoms of FI were graded using Wexner’s classification (including type of incontinence, pad usage, lifestyle). Wexner’s scores vary between 0, normal continence, and 20, total incontinence.
    End point type
    Secondary
    End point timeframe
    Change in the Wexner score at day 90 compared to baseline considered as Screening (day -92), in each treatment group
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: Change in Wexner Score
        arithmetic mean (standard deviation)
    -4.7 ( 5.7 )
    -4.9 ( 5.1 )
    -4.1 ( 5.3 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.479 [6]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [6] - Alpha level 5%
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.227 [7]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [7] - Alpha level 5%

    Secondary: Absolute change in Wexner Score 6 months

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    End point title
    		 Absolute change in Wexner Score 6 months
    End point description
    Symptoms of FI were graded using Wexner’s classification (including type of incontinence, pad usage, lifestyle). Wexner’s scores vary between 0, normal continence, and 20, total incontinence.
    End point type
    Secondary
    End point timeframe
    Change in the Wexner score at day 180 compared to baseline considered as Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: absolute change Wexner Score
        arithmetic mean (standard deviation)
    -4.6 ( 5.7 )
    -5.4 ( 5.5 )
    -5.3 ( 6.0 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.588 [8]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [8] - Alpha level 5%
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.869 [9]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [9] - Alpha level 5%

    Secondary: Absolute change visual analogue scale (VAS) 3 months

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    End point title
    		 Absolute change visual analogue scale (VAS) 3 months
    End point description
    The individual perception of FI complaints will be evaluated by each patient using a standardized VAS. The VAS is an instrument that measures a characteristic or attitude believed to range across a continuum of values and cannot easily be directly measured. It is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end. The patient should mark the VAS with a vertical line representing his perception of the individual FI status. In this study, the two endpoints of the VAS are defined as “no complaints at all” (0 mm) and “worst complaints imaginable” (100 mm).
    End point type
    Secondary
    End point timeframe
    Change in the Visual Analogue Scale (VAS) at day 90 compared to baseline (day 0), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: cm
        arithmetic mean (standard deviation)
    -1.3 ( 2.1 )
    -1.1 ( 2.1 )
    -1.0 ( 1.7 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.361 [10]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [10] - Alpha level of 5%
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    Placebo v HCC group
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.28 [11]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [11] - Alpha level 5%

    Secondary: Absolute change visual analogue scale (VAS) 6 months

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    End point title
    		 Absolute change visual analogue scale (VAS) 6 months
    End point description
    The individual perception of FI complaints will be evaluated by each patient using a standardized VAS. The VAS is an instrument that measures a characteristic or attitude believed to range across a continuum of values and cannot easily be directly measured. It is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end. The patient should mark the VAS with a vertical line representing his perception of the individual FI status. In this study, the two endpoints of the VAS are defined as “no complaints at all” (0 mm) and “worst complaints imaginable” (100 mm).
    End point type
    Secondary
    End point timeframe
    Change in the Visual Analogue Scale (VAS) at day 180 compared to baseline (day 0), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: cm
        arithmetic mean (standard deviation)
    -1.1 ( 2.3 )
    -1.3 ( 2.2 )
    -1.2 ( 2.0 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.678 [12]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [12] - Alpha level 5%
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.665 [13]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [13] - Alpha level of 5%

    Secondary: Absolute change visual analogue scale (VAS) 12 months

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    End point title
    		 Absolute change visual analogue scale (VAS) 12 months
    End point description
    The individual perception of FI complaints will be evaluated by each patient using a standardized VAS. The VAS is an instrument that measures a characteristic or attitude believed to range across a continuum of values and cannot easily be directly measured. It is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end. The patient should mark the VAS with a vertical line representing his perception of the individual FI status. In this study, the two endpoints of the VAS are defined as “no complaints at all” (0 mm) and “worst complaints imaginable” (100 mm).
    End point type
    Secondary
    End point timeframe
    Change in the Visual Analogue Scale (VAS) at day 360 compared to baseline (day 0), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: cm
        arithmetic mean (standard deviation)
    -1.2 ( 2.6 )
    -1.7 ( 2.6 )
    -1.0 ( 1.9 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.547 [14]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [14] - Alpha level 5%
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.356 [15]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [15] - Alpha level 5%

    Secondary: Incontinence Episode Frequency Reduction >= 50% (1 month)

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    End point title
    		 Incontinence Episode Frequency Reduction >= 50% (1 month)
    End point description
    End point type
    Secondary
    End point timeframe
    Frequency of response measured as a reduction of the frequency of incontinence episodes by more than 50% under treatment (from day 1 until day 28) compared to the baseline period (day -28 to day -1) , in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: number of patients
    22
    20
    13
    No statistical analyses for this end point

    Secondary: Incontinence Episode Frequency Reduction >= 50% (3 months)

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    End point title
    		 Incontinence Episode Frequency Reduction >= 50% (3 months)
    End point description
    End point type
    Secondary
    End point timeframe
    Frequency of response measured as a reduction of the frequency of incontinence episodes by more than 50% under treatment (from day 62 to day 89 ) compared to the baseline period (day -28 to day -1) , in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: number of patients
    35
    34
    28
    No statistical analyses for this end point

    Secondary: Incontinence Episode Frequency Reduction >= 50% (6 months)

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    End point title
    		 Incontinence Episode Frequency Reduction >= 50% (6 months)
    End point description
    End point type
    Secondary
    End point timeframe
    Frequency of response measured as a reduction of the frequency of incontinence episodes by more than 50% under treatment (from day 152 to day 179 ) compared to the baseline period (day -28 to day -1) , in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: number of patients
    41
    37
    34
    No statistical analyses for this end point

    Secondary: Incontinence Episode Frequency Reduction >= 50% (12 months)

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    End point title
    		 Incontinence Episode Frequency Reduction >= 50% (12 months)
    End point description
    End point type
    Secondary
    End point timeframe
    Frequency of response measured as a reduction of the frequency of incontinence episodes by more than 50% under treatment (from day 332 to day 359) compared to the baseline period (day -28 to day -1) , in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    77
    Units: number of patients
    39
    40
    31
    No statistical analyses for this end point

    Secondary: Remission rate 3 months

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    End point title
    		 Remission rate 3 months
    End point description
    End point type
    Secondary
    End point timeframe
    Frequency of patients in remission (remission = less than 3 incontinence episodes frequency during the 28 days period preceding V3, day 62 to day 89)
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: number of patients
    28
    27
    29
    No statistical analyses for this end point

    Secondary: Remission rate 6 months

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    End point title
    		 Remission rate 6 months
    End point description
    End point type
    Secondary
    End point timeframe
    Frequency of patients in remission (remission = less than 3 incontinence episodes frequency during the 28 days period preceding V4 (day 152 to day 179)
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: number of patients
    32
    31
    34
    No statistical analyses for this end point

    Secondary: Remission rate 12 months

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    End point title
    		 Remission rate 12 months
    End point description
    End point type
    Secondary
    End point timeframe
    Frequency of patients in remission (remission = less than 3 incontinence episodes frequency during the 28 days period preceding V5 (from day 332 to day 359).
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    75
    79
    Units: number of patients in remission
    30
    31
    28
    No statistical analyses for this end point

    Secondary: Anorectal Manometry (absolute change of length of the anal canal)

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    End point title
    		 Anorectal Manometry (absolute change of length of the anal canal)
    End point description
    The manometric evaluation before and after cell implantation enables measurement of the maximal and mean resting and squeeze pressures of the anal sphincter and the length of the anal canal. A low resting pressure indicates a dysfunction of the internal anal sphincter, whereas a low voluntary squeeze pressure indicates an external anal sphincter dysfunction.
    End point type
    Secondary
    End point timeframe
    Changes in the anorectal manometry data at day 180 compared to baseline (considered as screening, day-92), in each treatment group
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    79
    Units: mm
        arithmetic mean (standard deviation)
    0.9 ( 5.1 )
    0.4 ( 5.4 )
    0.7 ( 6.6 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.701
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.856
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Anorectal Manometry (absolute change resting pressure)

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    End point title
    		 Anorectal Manometry (absolute change resting pressure)
    End point description
    The manometric evaluation before and after cell implantation enables measurement of the maximal and mean resting and squeeze pressures of the anal sphincter and the length of the anal canal. A low resting pressure indicates a dysfunction of the internal anal sphincter, whereas a low voluntary squeeze pressure indicates an external anal sphincter dysfunction.
    End point type
    Secondary
    End point timeframe
    Changes in the anorectal manometry data at day 180 compared to baseline (considered as screening, day-92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    78
    Units: mmHg
        arithmetic mean (standard deviation)
    1.9 ( 21.6 )
    -1.8 ( 20.5 )
    -6.3 ( 17.3 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.009 [16]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [16] - Alpha level 2.5%
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.176
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Anorectal Manometry (absolute change maximum squeeze pressure)

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    End point title
    		 Anorectal Manometry (absolute change maximum squeeze pressure)
    End point description
    The manometric evaluation before and after cell implantation enables measurement of the maximal and mean resting and squeeze pressures of the anal sphincter and the length of the anal canal. A low resting pressure indicates a dysfunction of the internal anal sphincter, whereas a low voluntary squeeze pressure indicates an external anal sphincter dysfunction.
    End point type
    Secondary
    End point timeframe
    Changes in the anorectal manometry data at day 180 compared to baseline (considered as screening, day-92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    78
    Units: mmHg
        arithmetic mean (standard deviation)
    1.1 ( 51.6 )
    -0.3 ( 40.0 )
    3.6 ( 41.2 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.282
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.599
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Anorectal Manometry (absolute change first sensation)

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    End point title
    		 Anorectal Manometry (absolute change first sensation)
    End point description
    The manometric evaluation before and after cell implantation enables measurement of the maximal and mean resting and squeeze pressures of the anal sphincter and the length of the anal canal. A low resting pressure indicates a dysfunction of the internal anal sphincter, whereas a low voluntary squeeze pressure indicates an external anal sphincter dysfunction.
    End point type
    Secondary
    End point timeframe
    Changes in the anorectal manometry data at day 180 compared to baseline (considered as screening, day-92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    78
    Units: ml
        arithmetic mean (standard deviation)
    13.8 ( 31.8 )
    9.7 ( 36.1 )
    10.9 ( 30.3 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.685
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.605
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Anorectal Manometry (absolute change desire to defacate)

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    End point title
    		 Anorectal Manometry (absolute change desire to defacate)
    End point description
    The manometric evaluation before and after cell implantation enables measurement of the maximal and mean resting and squeeze pressures of the anal sphincter and the length of the anal canal. A low resting pressure indicates a dysfunction of the internal anal sphincter, whereas a low voluntary squeeze pressure indicates an external anal sphincter dysfunction.
    End point type
    Secondary
    End point timeframe
    Changes in the anorectal manometry data at day 180 compared to baseline (considered as screening, day-92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    81
    74
    76
    Units: ml
        arithmetic mean (standard deviation)
    21.3 ( 46.6 )
    19.9 ( 38.5 )
    17.8 ( 42.9 )
    No statistical analyses for this end point

    Secondary: Anorectal Manometry (absolute change urgency to defacate)

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    End point title
    		 Anorectal Manometry (absolute change urgency to defacate)
    End point description
    The manometric evaluation before and after cell implantation enables measurement of the maximal and mean resting and squeeze pressures of the anal sphincter and the length of the anal canal. A low resting pressure indicates a dysfunction of the internal anal sphincter, whereas a low voluntary squeeze pressure indicates an external anal sphincter dysfunction.
    End point type
    Secondary
    End point timeframe
    Changes in the anorectal manometry data at day 180 compared to baseline (considered as screening, day-92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    78
    71
    75
    Units: ml
        arithmetic mean (standard deviation)
    25.7 ( 47.0 )
    22.6 ( 55.0 )
    19.3 ( 52.3 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.248
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.531
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Anorectal Manometry (absolute change maximum tolerable volume)

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    End point title
    		 Anorectal Manometry (absolute change maximum tolerable volume)
    End point description
    The manometric evaluation before and after cell implantation enables measurement of the maximal and mean resting and squeeze pressures of the anal sphincter and the length of the anal canal. A low resting pressure indicates a dysfunction of the internal anal sphincter, whereas a low voluntary squeeze pressure indicates an external anal sphincter dysfunction.
    End point type
    Secondary
    End point timeframe
    Changes in the anorectal manometry data at day 180 compared to baseline (considered as screening, day-92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    74
    65
    70
    Units: ml
        arithmetic mean (standard deviation)
    32.5 ( 50.8 )
    28.2 ( 54.5 )
    17.6 ( 59.7 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.068
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    135
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.244
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change lifestyle subscale score) 3 months

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    End point title
    		 FI Quality of Life (absolute change lifestyle subscale score) 3 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) lifestyle score (from day 62 until day 89) compared to the baseline period (day -28 to day -1).
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    74
    79
    Units: Lifestyle subscale score
        arithmetic mean (standard deviation)
    0.5 ( 0.6 )
    0.4 ( 0.7 )
    0.4 ( 0.7 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.487
    Method
    		 t-test, 1-sided
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.568
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change lifestyle subscale score) 6 months

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    End point title
    		 FI Quality of Life (absolute change lifestyle subscale score) 6 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) lifestyle score at day 180 compared to baseline considered at Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    81
    74
    79
    Units: Lifestyle subscale score
        arithmetic mean (standard deviation)
    0.6 ( 0.7 )
    0.5 ( 0.7 )
    0.5 ( 0.7 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.69
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.702
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change lifestyle subscale score) 12 months

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    End point title
    		 FI Quality of Life (absolute change lifestyle subscale score) 12 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) lifestyle score at day 360 compared to baseline considered at Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    55
    55
    Units: Lifestyle subscale score
        arithmetic mean (standard deviation)
    0.5 ( 0.8 )
    0.6 ( 0.8 )
    0.4 ( 0.6 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    Placebo v LCC group
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.311
    Method
    		 t-test, 1-sided
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.266
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change coping/behavior score) 3 months

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    End point title
    		 FI Quality of Life (absolute change coping/behavior score) 3 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) coping/behavior score (from day 62 until day 89) compared to the baseline period (day -28 to day -1).
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    74
    79
    Units: coping/behavior subscale score
        arithmetic mean (standard deviation)
    0.5 ( 0.7 )
    0.6 ( 0.7 )
    0.6 ( 0.7 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.425
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change coping/behavior score) 6 months

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    End point title
    		 FI Quality of Life (absolute change coping/behavior score) 6 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) coping/behavior score at day 180 compared to baseline considered at Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    79
    Units: coping/behavior subscale score
        arithmetic mean (standard deviation)
    0.6 ( 0.7 )
    0.7 ( 0.7 )
    0.6 ( 0.7 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.577
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.262
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change coping/behavior score) 12 months

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    End point title
    		 FI Quality of Life (absolute change coping/behavior score) 12 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) coping/behavior score at day 360 compared to baseline considered at Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    55
    55
    Units: Coping/behavior subscale score
        arithmetic mean (standard deviation)
    0.5 ( 0.7 )
    0.7 ( 0.8 )
    0.5 ( 0.8 )
    No statistical analyses for this end point

    Secondary: FI Quality of Life (absolute change depression/self-perception) 3 months

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    End point title
    		 FI Quality of Life (absolute change depression/self-perception) 3 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) depression/self-perception score (from day 62 until day 89) compared to the baseline period (day -28 to day -1).
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    78
    74
    76
    Units: Depression subscale score
        arithmetic mean (standard deviation)
    0.4 ( 0.7 )
    0.4 ( 0.7 )
    0.4 ( 0.7 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.528
    Method
    		 t-test, 1-sided
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    Placebo v HCC group
    Number of subjects included in analysis
    150
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.943
    Method
    		 t-test, 1-sided
    Confidence interval

    Secondary: FI Quality of Life (absolute change depression/self-perception) 6 months

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    End point title
    		 FI Quality of Life (absolute change depression/self-perception) 6 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) depression/self-perception score at day 180 compared to baseline considered at Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    80
    74
    77
    Units: Depression subscale score
        arithmetic mean (standard deviation)
    0.5 ( 0.7 )
    0.5 ( 0.7 )
    0.4 ( 0.7 )
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    151
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.838
    Method
    		 t-test, 1-sided
    Confidence interval
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    157
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.545
    Method
    		 t-test, 1-sided
    Confidence interval

    Secondary: FI Quality of Life (absolute change depression/self-perception) 12 months

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    End point title
    		 FI Quality of Life (absolute change depression/self-perception) 12 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) depression / self-perception score at day 360 compared to baseline considered at Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    55
    54
    Units: Depression subscale score
        arithmetic mean (standard deviation)
    0.3 ( 0.8 )
    0.3 ( 0.6 )
    0.4 ( 0.7 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.441
    Method
    		 t-test, 1-sided
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.54
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change embarrassment) 3 months

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    End point title
    		 FI Quality of Life (absolute change embarrassment) 3 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) embarrassment score (from day 62 until day 89) compared to the baseline period (day -28 to day -1).
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    83
    74
    79
    Units: Embarrassment subscale score
        arithmetic mean (standard deviation)
    0.6 ( 0.8 )
    0.7 ( 0.8 )
    0.6 ( 0.8 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.671
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.715
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change embarrassment) 6 months

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    End point title
    		 FI Quality of Life (absolute change embarrassment) 6 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) embarrassment score at day 180 compared to baseline considered at Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    79
    Units: Embarrassment subscale score
        arithmetic mean (standard deviation)
    0.6 ( 0.8 )
    0.8 ( 0.9 )
    0.7 ( 0.9 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.436
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.685
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change embarrassment) 12 months

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    End point title
    		 FI Quality of Life (absolute change embarrassment) 12 months
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    Change of Patient’s assessment based on the Quality of life questionnaire (QoL) embarrassment score at day 332 compared to baseline considered at Screening (day -92), in each treatment group.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    55
    55
    Units: Embarrassment subscale score
        arithmetic mean (standard deviation)
    0.5 ( 0.7 )
    0.9 ( 1.0 )
    0.5 ( 0.8 )
    Statistical analysis title
    		 LCC versus placebo
    Comparison groups
    LCC group v Placebo
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.818
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 HCC versus placebo
    Comparison groups
    HCC group v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.156
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: FI Quality of Life (absolute change total score)

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    End point title
    		 FI Quality of Life (absolute change total score)
    End point description
    The patients' health-related QoL before and after cell implantation will be assessed using the Rockwood Fecal Incontinence Quality of Life Scale. This validated QoL scale was developed to address issues specifically related to FI. It consists of 29 items with questions regarding the following areas of impact: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).
    End point type
    Secondary
    End point timeframe
    6 months post implantation
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    79
    74
    77
    Units: total score
        arithmetic mean (standard deviation)
    2.3 ( 2.5 )
    2.6 ( 2.6 )
    2.3 ( 2.7 )
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (very much improved)

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    End point title
    		 Clinical Global Impression (CGI) improvement (very much improved)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 180.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    79
    Units: number of patients
    14
    12
    13
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (much improved)

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    End point title
    		 Clinical Global Impression (CGI) improvement (much improved)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 180.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    79
    Units: number of patients
    21
    23
    22
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (minimally improved)

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    End point title
    		 Clinical Global Impression (CGI) improvement (minimally improved)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 180.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    75
    79
    Units: number of patients
    10
    10
    9
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (no change)

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    End point title
    		 Clinical Global Impression (CGI) improvement (no change)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 180.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    79
    Units: number of patients
    35
    27
    33
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (minimally worse)

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    End point title
    		 Clinical Global Impression (CGI) improvement (minimally worse)
    End point description
    End point type
    Secondary
    End point timeframe
    6 months post implantation
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    79
    Units: number of patients
    1
    2
    2
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (much worse)

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    End point title
    		 Clinical Global Impression (CGI) improvement (much worse)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 180.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    82
    74
    79
    Units: number of patients
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (very much improved)

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    End point title
    		 Clinical Global Impression (CGI) improvement (very much improved)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 360.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    56
    57
    Units: number of patients
    10
    14
    9
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (much improved)

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    End point title
    		 Clinical Global Impression (CGI) improvement (much improved)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 360.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    56
    57
    Units: number of patients
    14
    16
    9
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (minimally improved)

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    End point title
    		 Clinical Global Impression (CGI) improvement (minimally improved)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 360.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    56
    57
    Units: number of patients
    10
    8
    11
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (no change)

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    End point title
    		 Clinical Global Impression (CGI) improvement (no change)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 360.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    56
    57
    Units: number of patients
    21
    14
    23
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (minimally worse)

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    End point title
    		 Clinical Global Impression (CGI) improvement (minimally worse)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 360.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    56
    57
    Units: number of patients
    3
    3
    2
    No statistical analyses for this end point

    Secondary: Clinical Global Impression (CGI) improvement (much worse)

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    End point title
    		 Clinical Global Impression (CGI) improvement (much worse)
    End point description
    Improvement of fecal incontinence was assessed using the Clinical Global Impression scale, which is a standardized assessment tool that allow the physician to rate the severity of illness, change over time and efficiency of treatment, taking into account the patients’ clinical condition and the severity of side effects. The CGI scale is widely used in clinical studies as an outcome measure.
    End point type
    Secondary
    End point timeframe
    Investigator's assessment by the Clinical Global Impression (CGI-I) score at day 360.
    End point values
    		 LCC group HCC group Placebo
    Number of subjects analysed
    61
    75
    79
    Units: number of patients
    3
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    27 November 2013 to 19 October 2016
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 288 patients compose the safety set. 44 patients of the safety set did not receive any treatment and 37 thereof were not randomized.

    Reporting group title
    LCC group
    Reporting group description
    		 288 patients compose the safety set. 44 patients of the safety set did not receive any treatment and 37 thereof were not randomized.

    Reporting group title
    HCC group
    Reporting group description
    		 288 patients compose the safety set. 44 patients of the safety set did not receive any treatment and 37 thereof were not randomized.

    Serious adverse events
    		 Placebo LCC group HCC group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 81 (4.94%)
    7 / 87 (8.05%)
    7 / 76 (9.21%)
         number of deaths (all causes)
    0
    1
    0
         number of deaths resulting from adverse events
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer stage I, with cancer in situ
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    0 / 81 (0.00%)
    0 / 87 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Exposure during pregnancy
         subjects affected / exposed
    1 / 81 (1.23%)
    2 / 87 (2.30%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 81 (0.00%)
    0 / 87 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 81 (0.00%)
    0 / 87 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric injury
         subjects affected / exposed
    0 / 81 (0.00%)
    0 / 87 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Dolichocolon
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 81 (0.00%)
    0 / 87 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 87 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 87 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 87 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Hiatus hernia
         subjects affected / exposed
    0 / 81 (0.00%)
    0 / 87 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Postmenopausal haemorrhage
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic haematoma
         subjects affected / exposed
    0 / 81 (0.00%)
    0 / 87 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 87 (1.15%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo LCC group HCC group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    50 / 81 (61.73%)
    62 / 87 (71.26%)
    43 / 76 (56.58%)
    Investigations
    Investigations
         subjects affected / exposed
    2 / 81 (2.47%)
    6 / 87 (6.90%)
    4 / 76 (5.26%)
         occurrences all number
    12
    12
    12
    Injury, poisoning and procedural complications
    Injury, poisoning and precedural complications
         subjects affected / exposed
    5 / 81 (6.17%)
    5 / 87 (5.75%)
    8 / 76 (10.53%)
         occurrences all number
    18
    18
    18
    Vascular disorders
    Vascular disorders
         subjects affected / exposed
    3 / 81 (3.70%)
    4 / 87 (4.60%)
    6 / 76 (7.89%)
         occurrences all number
    13
    13
    13
    Surgical and medical procedures
    Surgical and medical procedures
         subjects affected / exposed
    3 / 81 (3.70%)
    4 / 87 (4.60%)
    5 / 76 (6.58%)
         occurrences all number
    3
    4
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 81 (6.17%)
    2 / 87 (2.30%)
    7 / 76 (9.21%)
         occurrences all number
    14
    14
    14
    General disorders and administration site conditions
    General disorders and administration site conditions
         subjects affected / exposed
    1 / 81 (1.23%)
    6 / 87 (6.90%)
    2 / 76 (2.63%)
         occurrences all number
    1
    6
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    5 / 81 (6.17%)
    7 / 87 (8.05%)
    5 / 76 (6.58%)
         occurrences all number
    17
    17
    17
    Constipation
         subjects affected / exposed
    2 / 81 (2.47%)
    5 / 87 (5.75%)
    3 / 76 (3.95%)
         occurrences all number
    10
    10
    10
    Respiratory, thoracic and mediastinal disorders
    Respiratory, thoracic and mediastinal disorders
         subjects affected / exposed
    4 / 81 (4.94%)
    5 / 87 (5.75%)
    1 / 76 (1.32%)
         occurrences all number
    4
    5
    1
    Psychiatric disorders
    Psychiatric disorders
         subjects affected / exposed
    3 / 81 (3.70%)
    5 / 87 (5.75%)
    3 / 76 (3.95%)
         occurrences all number
    3
    5
    3
    Musculoskeletal and connective tissue disorders
    Musculoskeletel and connective tissue disorder
         subjects affected / exposed
    8 / 81 (9.88%)
    8 / 87 (9.20%)
    10 / 76 (13.16%)
         occurrences all number
    26
    26
    26
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    10 / 81 (12.35%)
    10 / 87 (11.49%)
    10 / 76 (13.16%)
         occurrences all number
    30
    30
    30
    Urinary tract infection
         subjects affected / exposed
    5 / 81 (6.17%)
    1 / 87 (1.15%)
    2 / 76 (2.63%)
         occurrences all number
    8
    8
    8

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Sep 2012
    • Replacement of CRO • The study duration per patient was increased from 12 months to 24 months • The cell therapy doses were modified for both LCC and HCC groups. For LCC group, the dose was changed to 5 ± 1 x 106 cells instead of 30 ± 10 x 106 cells. For HCC group, the dose was changed to 50 ± 10 x 106 cells instead of 90 ± 20 x 106 cells. • Standardized pelvic muscle electrical stimulation was deleted from the protocol and the 3D sonography was added. • Adding of exclusion criteria: overlap repair and associated early atrophy of external anal sphincter, recurrent anal fistula disease, chronic diarrhea and disease or conditions (fever and/or diarrhea of unknown reasons (4 weeks), HAV (4 months), toxoplasmosis (6 months), osteomyelitis, Qfever, rheumatic fever, tuberculosis, or Salmonella) which has not been resolved within a timeframe prior to screening. Patients with positive results in bacteriological testing at visit-1 (Salmonella (Typhus), F. tularensis (Tularaemia), M. leprae (Leprosy), Brucella, Rickettsia) was added as an interim exclusion criterion. • The primary endpoint “incontinence episodes frequency, IEF” was changed for “Changes in IEF occurred under treatment (from baseline until day 180) compared to the baseline period (day -28 to day 0), in each treatment group”. • An independent, unblinded Safety Board was established by the Sponsor to periodically review the total incidence of AEs and deaths in the study. • The condition for performing the second implantation with the optimal cell count offered to patients of the placebo group was detailed
    14 Jun 2013
    • The recruitment period duration was extended from 4 months to 12 months. • Pelvic floor electrical stimulation was added as study procedure to rehabilitate and strengthen the pelvic floor muscles. Consequently, contraindications for the use of the electro stimulation device were added as exclusion criteria. • The condition for performing the second implantation with the optimal cell count was extended to patients from the LCC group. • Supportive documents (poster, leaflet and newspaper publications) were developed to boost patient recruitment.
    25 Feb 2014
    • The mention “with external anal sphincter weakness or sphincter damage” was deleted from the indication “Fecal incontinence (FI) in female and male patients”. • Several inclusion and exclusion criteria were clarified (reworded) and two new exclusion criteria were added: ”Patients with chemotherapy related neuropathy of the bowel and pelvis“ and “Patients with chronic constipation and/or overflow incontinence”. • Since the efficacy of the ATIMP was not expected in a short delay after the implantation of aSMDC, the assessment period of the primary endpoint was reviewed and adapted: “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”. The secondary endpoints were also modified accordingly. • The completion of Short Form-36 by the patients participating in the PharmacoEconomics study was added to allow a rough QALY calculation and primitive pricing analysis.
    15 Apr 2015
    • The follow-up period was extended. A follow-up period of 18 additional months after Visit 4 (i.e. up to 24 months post-implantation) was to be offered to the patient at Visit 4 though a specific informed consent form. The purpose of this additional follow-up period was to provide efficacy and safety data on a long-term follow-up. This follow-up period included two on-site visits at 6 months (Visit 5) and 18 months (Visit 6) after Visit 4. The secondary endpoints were modified accordingly. • The exclusion criteria about pregnancy was restricted until Visit 4 to allow patients to become pregnant during the follow-up period if they wished to. • The mention “with external anal sphincter weakness or sphincter damage” were reintroduced in the indication fecal incontinence as it better described the population selected for the study.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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