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    Clinical Trial Results:
    Phase II clinical trial to know the effectiveness and safety with a treatment based in a therapy with serical autologous white cells versus the use of platelet rich plasma in patients with rotulian and achilles tendinopathy

    Summary
    EudraCT number
    		 2017-002129-39
    Trial protocol
    		 ES  
    Global end of trial date
    22 Mar 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Jun 2022
    First version publication date
    15 Jun 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    XC.ROD.2017
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    XCELL Medical Solutions SL
    Sponsor organisation address
    C/ Fortuny, N.º 29, Piso 1º, Madrid, Spain, 28010
    Public contact
    Pablo García de la Riva, XCELL Medical Solutions SL, 34 620340632, pgdelariva@m2rlab.com
    Scientific contact
    Pablo García de la Riva, XCELL Medical Solutions SL, 34 620340632, pgdelariva@m2rlab.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
    28 Apr 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Mar 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Mar 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluate and compare the effectiveness in pain reduction and safety in a treatment based in a therapy with serical autologous white cells versus the use of platelet rich plasma with the commercial kit of GPS® III from Biomet Biologics.
    Protection of trial subjects
    The study was in compliance with ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 At the start of the study, the patients continued with the medications prescribed by their doctor. After the infiltrations, the patients were able to take paracetamol or opioid analgesics at standard doses in case of unbearable local pain. After 48 hours following each of the infiltrations, local cryotherapy can be used.
    Evidence for comparator
    		 The administration of the study treatment and its comparator were done in the same way using the same type of material.
    Actual start date of recruitment
    28 Oct 2019
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Safety
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 48
    Worldwide total number of subjects
    48
    EEA total number of subjects
    48
    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)
    47
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 48 patients who met the selection criteria were recruited for the study from October 28, 2019 to October 7, 2020. 8 patients were excluded due to screening failure (4), patient decision (3) and adverse event before treatment (1). Thus, 40 patients were randomized and all of them completed the study.

    Pre-assignment
    Screening details
    		 The principal investigator selected among the cases that came to his consultation, those that fit the patient profile defined by the selection criteria and that agreed to participate in the trial.

    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    The treatment was administered by a person other than the evaluator.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 XCell (Treatment)
    Arm description
    		 Autologous serum therapy with white blood cells (M2R-XCell)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Autologous serum therapy with white blood cells (M2R-XCell)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Infiltration
    Dosage and administration details
    Patellar tendon infiltration: It was injected by local intratendinous infiltration with a 21G needle. The doctor was guided by ultrasound to put the product in the damaged area. Depending on the extent of the lesion, between 4 and 8 cc. It was injected following the longitudinal axis of the tendon, from caudal to cephalad. To reach the most posterior area of ​​the tendon, infiltration was performed along the axial axis from the lateral to the medial aspect of the knee. Achilles tendon infiltration: It was injected by local intratendinous infiltration with a 21G needle. The doctor was guided by ultrasound to put the product in the damaged area. Depending on the extent of the lesion, between 3 and 5 cc. It was injected following the longitudinal axis of the tendon, from cephalic to caudal. The "peppering" technique was used, which consists of inserting the needle into the tendon, injecting part of the product, withdrawing without leaving the skin, redirecting and reinserting to deposi

    Arm title
    		 PRP (Control)
    Arm description
    		 Platelet Rich Plasma (PRP) with Biomet Biologics GPS® III Commercial Kit
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Platelet Rich Plasma (PRP) with Biomet Biologics GPS® III Commercial Kit
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Injection , Infiltration
    Dosage and administration details
    Patellar tendon infiltration: It was injected by local intratendinous infiltration with a 21G needle. The doctor was guided by ultrasound to put the product in the damaged area. Depending on the extent of the lesion, between 4 and 8 cc. It was injected following the longitudinal axis of the tendon, from caudal to cephalad. To reach the most posterior area of ​​the tendon, infiltration was performed along the axial axis from the lateral to the medial aspect of the knee. Achilles tendon infiltration: It was injected by local intratendinous infiltration with a 21G needle. The doctor was guided by ultrasound to put the product in the damaged area. Depending on the extent of the lesion, between 3 and 5 cc. It was injected following the longitudinal axis of the tendon, from cephalic to caudal. The "peppering" technique was used, which consists of inserting the needle into the tendon, injecting part of the product, withdrawing without leaving the skin, redirecting and reinserting to deposi

    Number of subjects in period 1 [1]
    		XCell (Treatment) PRP (Control)
    Started
    20
    20
    Completed
    20
    20
    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: 48 patients were recruited for the study from October 28, 2019 to October 7, 2020. Of the 48 patients, 8 were excluded due to screening failure (4), patient decision (3) and adverse event before treatment (one ). Therefore, 40 patients were randomized and treated.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    XCell (Treatment)
    Reporting group description
    		 Autologous serum therapy with white blood cells (M2R-XCell)

    Reporting group title
    PRP (Control)
    Reporting group description
    		 Platelet Rich Plasma (PRP) with Biomet Biologics GPS® III Commercial Kit

    Reporting group values
    		 XCell (Treatment) PRP (Control) Total
    Number of subjects
    		 20 20 40
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 19 20 39
        From 65-84 years
    		 1 0 1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 49.3 ( 12.9 ) 49.5 ( 7.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 7 6 13
        Male
    		 13 14 27
    Activity level
    Units: Subjects
        Professional
    		 18 15 33
        Amateur
    		 2 5 7
    Injured tendon
    Units: Subjects
        Patellar
    		 4 1 5
        Achilles
    		 16 19 35
    Dominant leg
    Units: Subjects
        Right
    		 13 15 28
        Left
    		 7 4 11
        Ambidextrous
    		 0 1 1
    Laterality of the lesion
    Units: Subjects
        Right
    		 13 7 20
        Left
    		 7 13 20
    Previous treatment with PRP
    PRP, Platelet Rich Plasma
    Units: Subjects
        Yes
    		 0 2 2
        No
    		 20 18 38
    Neovascularization
    Units: Subjects
        Yes
    		 9 7 16
        No
    		 11 13 24
    VISA
    Patellar tendinopathy severity index (VISA-P) or Achilles tendinopathy (VISA-A) to analyze the evolution of pain and the degree of severity of the injury. The Victorian Institute of Sport Assessment (VISA) scale allows a clinical classification based on symptom severity, functional capacity and sports capacity. The VISA questionnaire score ranges on a scale of 0 to 100, where the higher the score, the better the condition of the tendon.
    Units: points
        arithmetic mean (standard deviation)
    		 50.7 ( 18.6 ) 55.1 ( 14.3 ) -
    VAS
    VAS, subjective pain scale. The VAS score ranges on a scale from 0 to 10, with a higher score greater pain.
    Units: points
        arithmetic mean (standard deviation)
    		 4.9 ( 2.2 ) 4.9 ( 1.5 ) -
    Cincinnati function scale
    Sports assessment instrument: the Cincinnati Sports Activity Scale (CSAS). The Cincinnati questionnaire score ranges from 0 to 100, where the higher the score, the better the functionality.
    Units: points
        arithmetic mean (standard deviation)
    		 56.3 ( 14.5 ) 57.6 ( 11.9 ) -
    Weight
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 79.7 ( 17.4 ) 83.1 ( 15.7 ) -
    Height
    Units: points
        arithmetic mean (standard deviation)
    		 174.0 ( 11.6 ) 174.6 ( 10.2 ) -
    BMI
    BMI, Body mass index
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    		 26.1 ( 3.7 ) 27.1 ( 3.6 ) -
    Goniometry - Internal Rotation
    Units: degree
        arithmetic mean (standard deviation)
    		 20.8 ( 13.0 ) 23.3 ( 9.9 ) -
    Goniometry - External Rotation
    Units: degree
        arithmetic mean (standard deviation)
    		 9.5 ( 6.1 ) 11.8 ( 5.7 ) -
    Goniometry - Flexion
    Units: degree
        arithmetic mean (standard deviation)
    		 78.3 ( 34.5 ) 66.3 ( 24.4 ) -
    Goniometry - Extension
    Units: degree
        arithmetic mean (standard deviation)
    		 10.5 ( 13.9 ) 12.0 ( 8.3 ) -
    Ultrasound - Tendon thickness
    Units: centimetre
        arithmetic mean (standard deviation)
    		 8.9 ( 2.7 ) 8.4 ( 3.2 ) -
    Ultrasound - Section area
    Units: square centimetre
        arithmetic mean (standard deviation)
    		 5.6 ( 6.6 ) 9.7 ( 20.9 ) -
    Ultrasound - Thickness of the tendon at 1 cm from the point of insertion
    Units: degree
        arithmetic mean (standard deviation)
    		 4.0 ( 2.4 ) 4.1 ( 1.1 ) -
    Ultrasound - Difference in thicknesses
    Units: degree
        arithmetic mean (standard deviation)
    		 4.9 ( 3.3 ) 4.3 ( 3.3 ) -

    End points

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    End points reporting groups
    Reporting group title
    XCell (Treatment)
    Reporting group description
    		 Autologous serum therapy with white blood cells (M2R-XCell)

    Reporting group title
    PRP (Control)
    Reporting group description
    		 Platelet Rich Plasma (PRP) with Biomet Biologics GPS® III Commercial Kit

    Primary: Change in VISA questionnaire score at 24 weeks after treatment

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    End point title
    		 Change in VISA questionnaire score at 24 weeks after treatment
    End point description
    Patellar tendinopathy severity index (VISA-P) or Achilles tendinopathy (VISA-A) to analyze the evolution of pain and the degree of severity of the injury. The Victorian Institute of Sport Assessment (VISA) scale allows a clinical classification based on symptom severity, functional capacity and sports capacity. The VISA questionnaire score ranges on a scale of 0 to 100, where the higher the score, the better the condition of the tendon.
    End point type
    Primary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: Points
        arithmetic mean (standard deviation)
    24.8 ( 22.7 )
    22.8 ( 19.8 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Difference in VISA questionnaire from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.842
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.6
         upper limit
    		 13.5
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Difference in VISA questionnaire from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    24.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.1
         upper limit
    		 35.4
    Variability estimate
    Standard deviation
    Dispersion value
    22.7
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Difference in VISA questionnaire from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    22.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.5
         upper limit
    		 32.1
    Variability estimate
    Standard deviation
    Dispersion value
    19.8

    Primary: Change in VAS questionnaire score at 24 weeks after treatment

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    End point title
    		 Change in VAS questionnaire score at 24 weeks after treatment
    End point description
    VAS, subjective pain scale. The VAS score ranges on a scale from 0 to 10, with a higher score greater pain.
    End point type
    Primary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: Points
        arithmetic mean (standard deviation)
    -3.4 ( 2.6 )
    -3.7 ( 1.7 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Difference in VAS scale from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.381
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 1.3
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Difference in VAS scale from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 -2.2
    Variability estimate
    Standard deviation
    Dispersion value
    2.6
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Difference in VAS scale from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.5
         upper limit
    		 -2.9
    Variability estimate
    Standard deviation
    Dispersion value
    1.7

    Secondary: Change in Cincinnati Function Scale (CSAS) at 24 weeks after treatment

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    End point title
    		 Change in Cincinnati Function Scale (CSAS) at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: Points
        arithmetic mean (standard deviation)
    28.8 ( 15.1 )
    32.4 ( 15.7 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Difference in Cincinnati Function Scale (CSAS) from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.259
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.7
         upper limit
    		 4.4
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Difference in Cincinnati Function Scale (CSAS) from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Median difference (final values)
    Point estimate
    28.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 21.7
         upper limit
    		 35.8
    Variability estimate
    Standard deviation
    Dispersion value
    15.1
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Difference in Cincinnati Function Scale (CSAS) from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    32.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 25.1
         upper limit
    		 39.7
    Variability estimate
    Standard deviation
    Dispersion value
    15.7

    Secondary: Time to return to regular physical activity at 24 weeks after treatment

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    End point title
    		 Time to return to regular physical activity at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    16
    18
    Units: day
        arithmetic mean (standard deviation)
    60.3 ( 60.0 )
    38.2 ( 25.4 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in time to return to regular physical activity from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.558
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Ultrasound evolution (tendon thickness) at 24 weeks after treatment

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    End point title
    		 Ultrasound evolution (tendon thickness) at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: centimetre
        arithmetic mean (standard deviation)
    -1.3 ( 1.2 )
    -1.3 ( 1.9 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in tendon thickness (cm) from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.836
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Differences in tendon thickness (cm) from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 -0.8
    Variability estimate
    Standard deviation
    Dispersion value
    1.2
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Differences in tendon thickness (cm) from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.009
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 -0.3
    Variability estimate
    Standard deviation
    Dispersion value
    1.9

    Secondary: Neovascularization at 24 weeks after treatment

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    End point title
    		 Neovascularization at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: Absolute frecuency
        Yes
    8
    8
        No
    12
    12
    Statistical analysis title
    		 Change between baseline and 24 weeks of treatment
    Statistical analysis description
    Differences in neovascularization from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Change in range of motion with goniometer (Internal Rotation) at 24 weeks after treatment

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    End point title
    		 Change in range of motion with goniometer (Internal Rotation) at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: degree
        arithmetic mean (standard deviation)
    -0.8 ( 6.9 )
    -0.5 ( 4.8 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in internal rotation measured by the goniometer from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.448
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 3.2
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Differences in internal rotation measured by the goniometer from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 2.5
    Variability estimate
    Standard deviation
    Dispersion value
    6.9
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Differences in internal rotation measured by the goniometer from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.625
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 1.8
    Variability estimate
    Standard deviation
    Dispersion value
    4.8

    Secondary: Change in range of motion with goniometer (External Rotation) at 24 weeks after treatment

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    End point title
    		 Change in range of motion with goniometer (External Rotation) at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: degree
        arithmetic mean (standard deviation)
    1.0 ( 3.1 )
    -0.5 ( 3.6 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in external rotation measured by the goniometer from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.52
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 3.6
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Differences in external rotation measured by the goniometer from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 2.4
    Variability estimate
    Standard deviation
    Dispersion value
    3.1
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Differences in external rotation measured by the goniometer from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 1.2
    Variability estimate
    Standard deviation
    Dispersion value
    3.6

    Secondary: Change in range of motion with goniometer (Flexion) at 24 weeks after treatment

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    End point title
    		 Change in range of motion with goniometer (Flexion) at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: degree
        arithmetic mean (standard deviation)
    7.5 ( 13.5 )
    9.0 ( 19.9 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in flexion measured by the goniometer from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.711
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11
         upper limit
    		 8
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Differences in flexion measured by the goniometer from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.011
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 13.8
    Variability estimate
    Standard deviation
    Dispersion value
    13.5
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Differences in flexion measured by the goniometer from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.058
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 18.3
    Variability estimate
    Standard deviation
    Dispersion value
    19.9

    Secondary: Change in range of motion with goniometer (Extension) at 24 weeks after treatment

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    End point title
    		 Change in range of motion with goniometer (Extension) at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: degree
        arithmetic mean (standard deviation)
    0.4 ( 12.7 )
    0.0 ( 7.4 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in extension measured by the goniometer from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.482
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 4
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Differences in extension measured by the goniometer from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.075
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.5
         upper limit
    		 6.3
    Variability estimate
    Standard deviation
    Dispersion value
    12.7
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Differences in extension measured by the goniometer from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.951
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5
         upper limit
    		 3.5
    Variability estimate
    Standard deviation
    Dispersion value
    7.4

    Secondary: Ultrasound evolution (section area) at 24 weeks after treatment

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    End point title
    		 Ultrasound evolution (section area) at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: square centimetre
        arithmetic mean (standard deviation)
    -4.5 ( 6.5 )
    -4.0 ( 6.5 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in section area (cm2) from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.55
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Differences in section area (cm2) from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.5
         upper limit
    		 -1.4
    Variability estimate
    Standard deviation
    Dispersion value
    6.5
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Differences in section area (cm2) from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 -0.9
    Variability estimate
    Standard deviation
    Dispersion value
    6.5

    Secondary: Ultrasound evolution (tendon thickness at 1 cm from the point of insertion) at 24 weeks after treatment

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    End point title
    		 Ultrasound evolution (tendon thickness at 1 cm from the point of insertion) at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: centimetre
        arithmetic mean (standard deviation)
    -0.2 ( 1.8 )
    -0.3 ( 0.8 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in tendon thickness at 1 cm from the point of insertion (cm) from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.825
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Differences in tendon thickness at 1 cm from the point of insertion (cm) from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.772
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.6
    Variability estimate
    Standard deviation
    Dispersion value
    1.8
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Differences in tendon thickness at 1 cm from the point of insertion (cm) from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.19
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.1
    Variability estimate
    Standard deviation
    Dispersion value
    0.8

    Secondary: Difference between the maximum thickness and the thickness of the tendon at 1 cm from the point of insertion at 24 weeks after treatment

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    End point title
    		 Difference between the maximum thickness and the thickness of the tendon at 1 cm from the point of insertion at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: centimetre
        arithmetic mean (standard deviation)
    -1.1 ( 2.1 )
    -1.0 ( 1.9 )
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Difference between the maximum thickness and the thickness of the tendon at 1 cm from the point of insertion (cm) from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.595
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 Change from baseline to 24 week in XCell group
    Statistical analysis description
    Difference between the maximum thickness and the thickness of the tendon at 1 cm from the point of insertion from baseline to 24 weeks after treatment in XCell group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 -0.1
    Variability estimate
    Standard deviation
    Dispersion value
    2.1
    Statistical analysis title
    		 Change from baseline to 24 week in PRP group
    Statistical analysis description
    Difference between the maximum thickness and the thickness of the tendon at 1 cm from the point of insertion from baseline to 24 weeks after treatment in PRP group. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    PRP (Control) v XCell (Treatment)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.029
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 -0.1
    Variability estimate
    Standard deviation
    Dispersion value
    1.9

    Secondary: Satisfaction level at 24 weeks after treatment

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    End point title
    		 Satisfaction level at 24 weeks after treatment
    End point description
    End point type
    Secondary
    End point timeframe
    Difference from baseline to 24 weeks after treatment
    End point values
    		 XCell (Treatment) PRP (Control)
    Number of subjects analysed
    20
    20
    Units: Absolute frecuency
        Poor
    3
    0
        Acceptable
    3
    5
        Good
    8
    11
        Excellent
    6
    4
    Statistical analysis title
    		 Differences between groups
    Statistical analysis description
    Differences in satisfacion level from baseline to 24 weeks after treatment. Student's t-test was used to assess potential differences between treatment groups.
    Comparison groups
    XCell (Treatment) v PRP (Control)
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.267
    Method
    		 t-test, 2-sided
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Overall period, from 28/10/2019 to 22/03/2021
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    XCell (Treatment)
    Reporting group description
    		 Autologous serum therapy with white blood cells (M2R-XCell)

    Reporting group title
    PRP (Control)
    Reporting group description
    		 Platelet Rich Plasma (PRP) with Biomet Biologics GPS® III Commercial Kit

    Serious adverse events
    		 XCell (Treatment) PRP (Control)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 XCell (Treatment) PRP (Control)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    Musculoskeletal and connective tissue disorders
    Plantar fasciitis
    Additional description: An adverse event occurred in a patient treated with PRP (5.0%). AE was plantar fasciitis in the left foot of mild intensity and unrelated to study treatment. The patient was left-handed and was treated for the Achilles tendon of the left foot.
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Dec 2017
    Changes in the treatment part and addition of a center.
    15 Mar 2019
    The inclusion of patients with Achilles tendinopathy and addition of a new center.
    18 Sep 2019
    Addition of 1 new center and change of Principal Investigator from another center

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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