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    Clinical Trial Results:
    A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of SNF472 When added to Background Care for the Treatment of Calciphylaxis.

    Summary
    EudraCT number
    2018-001301-90
    Trial protocol
    GB   ES   PL   BE   IT  
    Global end of trial date
    24 Oct 2022

    Results information
    Results version number
    v2(current)
    This version publication date
    17 Dec 2023
    First version publication date
    30 Nov 2023
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    The email of Scientific and Public contact has been updated.

    Trial information

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    Trial identification
    Sponsor protocol code
    SNFCT2017-06
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT04195906
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Sanifit Therapeutics S.A., A CSL Vifor Pharma Company
    Sponsor organisation address
    PARC BIT. Europa Building. 2nd floor, Palma, Spain, 07121
    Public contact
    Peter Szecsödy, Sanifit Therapeutics S.A , +41 588529079, clinicaltrials@cslbehring.com
    Scientific contact
    Peter Szecsödy, Sanifit Therapeutics S.A , +41 588529079, clinicaltrials@cslbehring.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
    12 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Oct 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Oct 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of SNF472 compared with placebo when added to background care for the treatment of calciphylaxis. To evaluate the safety and tolerability of SNF472 compared with placebo when added to background care for the treatment of calciphylaxis.
    Protection of trial subjects
    The study was conducted in accordance with the principles of the Declaration of Helsinki including amendments in force up to and including the time the study was conducted. The study was conducted in compliance with the International Council for Harmonisation (ICH) E6 Guideline for Good Clinical Practice (GCP), Committee for Proprietary Medicinal Products Guideline (CPMP/ICH/135/95), compliant with the EU Clinical Trial Directive (Directive 2001/20/EC) and/or the Code of Federal Regulations (CFR) for informed consent and protection of subject rights (21 CFR, Parts 50 and 56), and in accordance with United States Food and Drug Administration (US FDA) regulations. A data and safety monitoring board (DSMB) was established and was responsible for safeguarding the interests of trial participants and assessing the safety of the interventions during the trial.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    14 Dec 2019
    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
    Poland: 3
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    United States: 64
    Worldwide total number of subjects
    71
    EEA total number of subjects
    5
    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)
    54
    From 65 to 84 years
    16
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 148 participants were screened in 48 sites in 5 countries; 77 participants were not enrolled because they were screen failures (did not meet eligibility criteria). A total of 71 participants were randomized in the study to receive SNF472 or placebo.

    Period 1
    Period 1 title
    Part 1
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor
    Blinding implementation details
    Part 1 was performed in a double-blind manner. The Investigator, site staff, subjects, and Sponsor staff (including designees) involved in the conduct of the study and data management remained blinded to the treatment assignment for Part 1 for the duration of the study including Part 2 and follow-up until the study database lock, except if unblinding was required.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    SNF472
    Arm description
    Part 1 (double-blind period): Participants received SNF472 for 12 weeks in addition to their background care.
    Arm type
    Experimental

    Investigational medicinal product name
    SNF472
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.

    Arm title
    Placebo
    Arm description
    Part 1 (double-blind period) Participants received placebo for 12 weeks in addition to their background care.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose: Matching placebo (saline) diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks

    Number of subjects in period 1
    SNF472 Placebo
    Started
    37
    34
    Completed
    34
    26
    Not completed
    3
    8
         Consent withdrawn by subject
    -
    1
         Adverse event, non-fatal
    3
    7
    Period 2
    Period 2 title
    Part 2
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded
    Blinding implementation details
    Open-label treatment period

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    SNF472
    Arm description
    Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care.
    Arm type
    Experimental

    Investigational medicinal product name
    SNF472
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.

    Arm title
    Placebo
    Arm description
    Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care.
    Arm type
    Experimental

    Investigational medicinal product name
    SNF472
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.

    Number of subjects in period 2
    SNF472 Placebo
    Started
    34
    26
    Completed
    32
    19
    Not completed
    2
    7
         Consent withdrawn by subject
    -
    3
         Adverse event, non-fatal
    1
    1
         Other
    1
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    SNF472
    Reporting group description
    Part 1 (double-blind period): Participants received SNF472 for 12 weeks in addition to their background care.

    Reporting group title
    Placebo
    Reporting group description
    Part 1 (double-blind period) Participants received placebo for 12 weeks in addition to their background care.

    Reporting group values
    SNF472 Placebo Total
    Number of subjects
    37 34 71
    Age categorical
    Units: Subjects
        <=18 years
    0 0 0
        Between 18 and 65 years
    27 27 54
        >=65 years
    10 7 17
    Gender categorical
    Units: Subjects
        Female
    23 21 44
        Male
    14 13 27

    End points

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    End points reporting groups
    Reporting group title
    SNF472
    Reporting group description
    Part 1 (double-blind period): Participants received SNF472 for 12 weeks in addition to their background care.

    Reporting group title
    Placebo
    Reporting group description
    Part 1 (double-blind period) Participants received placebo for 12 weeks in addition to their background care.
    Reporting group title
    SNF472
    Reporting group description
    Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care.

    Reporting group title
    Placebo
    Reporting group description
    Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care.

    Primary: Absolute Change in the BWAT - CUA Score for the Primary Lesion

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    End point title
    Absolute Change in the BWAT - CUA Score for the Primary Lesion
    End point description
    The Bates Jensen Wound Assessment Tool (BWAT) CUA score ranges from a minimum score of 8 (best) to a maximum score of 40 (worst). BWAT-CUA= Bates-Jensen Wound Assessment Tool-Calcific Uremic Arteriolopathy
    End point type
    Primary
    End point timeframe
    from Baseline to Week 12
    End point values
    SNF472 Placebo
    Number of subjects analysed
    37
    34
    Units: score on a scale
        arithmetic mean (standard deviation)
    -5.3 ( 5.18 )
    -6.0 ( 6.17 )
    Statistical analysis title
    Mixed model for repeated measures
    Statistical analysis description
    The MMRM model includes fixed effect terms for randomized treatment, visit, baseline sodium thiosulfate use, baseline BWAT-CUA score and visit by randomized treatment interaction. Participant is fitted as random effect and an unstructured variance-covariance matrix is used.
    Comparison groups
    SNF472 v Placebo
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.877
    Method
    Mixed models analysis
    Parameter type
    Least Squares Mean Difference
    Point estimate
    0.27
    Confidence interval
         level
    96%
         sides
    2-sided
         lower limit
    -2.46
         upper limit
    3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.328

    Secondary: Absolute Change in Pain Visual Analog Score

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    End point title
    Absolute Change in Pain Visual Analog Score
    End point description
    The Pain Visual Analog Scale (VAS) score ranges from a minimum score of 0 (no pain) to 100 (worst possible pain).
    End point type
    Secondary
    End point timeframe
    from Baseline to Week 12
    End point values
    SNF472 Placebo
    Number of subjects analysed
    37
    34
    Units: score on a scale
        arithmetic mean (standard deviation)
    -19.5 ( 26.89 )
    -32.2 ( 38.53 )
    Statistical analysis title
    Mixed model for repeated measures
    Statistical analysis description
    The MMRM model includes fixed effect terms for randomized treatment, visit, baseline sodium thiosulfate use, baseline BWAT-CUA score and visit by randomized treatment interaction. Participant is fitted as random effect and an unstructured variance-covariance matrix is used.
    Comparison groups
    Placebo v SNF472
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.146
    Method
    Mixed models analysis
    Parameter type
    Least Squares Mean Difference
    Point estimate
    11.49
    Confidence interval
         level
    96%
         sides
    2-sided
         lower limit
    -4.8
         upper limit
    27.78
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.93

    Secondary: Absolute Change in the Wound-Quality of Life Score

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    End point title
    Absolute Change in the Wound-Quality of Life Score
    End point description
    The Wound Quality of Life scale is a validated self-assessment tool that has been shown to be feasible for assessing health-related quality of life in patients with chronic wounds. Lower scores are associated with a better quality of life as reported by the patient.
    End point type
    Secondary
    End point timeframe
    from Baseline to Week 12
    End point values
    SNF472 Placebo
    Number of subjects analysed
    37
    34
    Units: score on a scale
        arithmetic mean (standard deviation)
    -0.67 ( 0.798 )
    -0.74 ( 1.175 )
    Statistical analysis title
    Mixed model for repeated measures
    Statistical analysis description
    The MMRM model includes fixed effect terms for randomized treatment, visit, baseline sodium thiosulfate use, baseline BWAT-CUA score and visit by randomized treatment interaction. Participant is fitted as random effect and an unstructured variance-covariance matrix is used.
    Comparison groups
    SNF472 v Placebo
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.706
    Method
    Mixed models analysis
    Parameter type
    Least Squares Mean Difference
    Point estimate
    0.09
    Confidence interval
         level
    96%
         sides
    2-sided
         lower limit
    -0.38
         upper limit
    0.56
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.237

    Secondary: Absolute Change in the BWAT Total Score for the Primary Lesion

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    End point title
    Absolute Change in the BWAT Total Score for the Primary Lesion
    End point description
    The Bates Jensen Wound Assessment Tool (BWAT) score ranges from a minimum score of 9 (best) to a maximum score of 65 (worst) score.
    End point type
    Secondary
    End point timeframe
    from Baseline to Week 12
    End point values
    SNF472 Placebo
    Number of subjects analysed
    37
    34
    Units: score on a scale
        arithmetic mean (standard deviation)
    -11.0 ( 9.85 )
    -11.7 ( 12.23 )
    Statistical analysis title
    Mixed model for repeated measures
    Statistical analysis description
    The MMRM model includes fixed effect terms for randomized treatment, visit, baseline sodium thiosulfate use, baseline BWAT-CUA score and visit by randomized treatment interaction. Participant is fitted as random effect and an unstructured variance-covariance matrix is used.
    Comparison groups
    SNF472 v Placebo
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.995
    Method
    Mixed models analysis
    Parameter type
    Least Squares Mean Difference
    Point estimate
    -0.02
    Confidence interval
         level
    96%
         sides
    2-sided
         lower limit
    -5.27
         upper limit
    5.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.63

    Secondary: Qualitative Wound Image Evaluation for the Primary Lesion

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    End point title
    Qualitative Wound Image Evaluation for the Primary Lesion
    End point description
    A qualitative assessment (Worsened, Equal to, or Improved Relative to Baseline) was assigned
    End point type
    Secondary
    End point timeframe
    at Week 12
    End point values
    SNF472 Placebo
    Number of subjects analysed
    37
    34
    Units: Count of Participants
        Worsened
    6
    7
        Equal
    0
    1
        Improved
    23
    18
        Missing
    8
    8
    Statistical analysis title
    Logistic regression odds ratio
    Statistical analysis description
    This model includes the stratification factor sodium thiosulfate use at baseline and the treatment as covariates. As there is only a measure post-baseline, a logistic regression model was run instead of a generalized estimating equations model. The odds ratio displayed is the odds ratio of having an improved result of SNF472 versus Placebo. The results 'Worsened', 'Equal', and 'Missing' are combined in one category and it is the reference for the odds ratio calculation.
    Comparison groups
    SNF472 v Placebo
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.384
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.58
         upper limit
    4.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.498

    Secondary: Rate of Change in Opioid Use as Measured in Morphine Milligram Equivalents (MME)

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    End point title
    Rate of Change in Opioid Use as Measured in Morphine Milligram Equivalents (MME)
    End point description
    Change from baseline in opioid use MME = Morphine Milligram Equivalents
    End point type
    Secondary
    End point timeframe
    from Baseline to Week 12
    End point values
    SNF472 Placebo
    Number of subjects analysed
    37
    34
    Units: MME/week
        least squares mean (standard error)
    0.46 ( 0.461 )
    -0.11 ( 0.499 )
    Statistical analysis title
    Mixed model for repeated measures
    Statistical analysis description
    The MMRM model includes fixed effect terms for randomized treatment, continuous variables maintenance opioid dose, Week (1 to 12) and Week by randomized treatment interaction. The random coefficients are the intercept and Week as a continuous variable.
    Comparison groups
    SNF472 v Placebo
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.406
    Method
    Mixed models analysis
    Parameter type
    Difference in slopes between arms
    Point estimate
    0.57
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.79
         upper limit
    1.93
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    SNF472 - Safety Analysis Population (Part 1)
    Reporting group description
    Participants who received SNF472 treatment during part 1 (Double-blind Period).

    Reporting group title
    SNF472 Open label - Safety Analysis Population (Part 2)
    Reporting group description
    Participants who received SNF472 treatment during part 2 (Open-label)

    Reporting group title
    Placebo - Safety Analysis Population (Part 1)
    Reporting group description
    Participants who received placebo during part 1 (Double-blind Period).

    Serious adverse events
    SNF472 - Safety Analysis Population (Part 1) SNF472 Open label - Safety Analysis Population (Part 2) Placebo - Safety Analysis Population (Part 1)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 38 (34.21%)
    18 / 60 (30.00%)
    17 / 33 (51.52%)
         number of deaths (all causes)
    1
    1
    6
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    Hypertensive urgency
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    Peripheral vascular disorder
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Impaired healing
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Arteriovenous graft site haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Spinal fracture
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Atrial flutter
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Cardiac arrest
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 60 (1.67%)
    2 / 33 (6.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Cardiac failure
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Cardiac failure acute
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 60 (1.67%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Mitral valve incompetence
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Encephalopathy
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 38 (0.00%)
    2 / 60 (3.33%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dieulafoy's vascular malformation
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    Cholelithiasis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Skin and subcutaneous tissue disorders
    Skin necrosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    End stage renal disease
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         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
    Arteriovenous fistula site infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    COVID-19
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Cellulitis
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 60 (1.67%)
    3 / 33 (9.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 60 (1.67%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 38 (2.63%)
    2 / 60 (3.33%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 60 (1.67%)
    2 / 33 (6.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tooth infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Osteomyelitis
         subjects affected / exposed
    0 / 38 (0.00%)
    2 / 60 (3.33%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    Postoperative wound infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 60 (1.67%)
    0 / 33 (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
    Metabolism and nutrition disorders
    Calciphylaxis
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 60 (0.00%)
    5 / 33 (15.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Hypervolaemia
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 60 (1.67%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 60 (0.00%)
    0 / 33 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    SNF472 - Safety Analysis Population (Part 1) SNF472 Open label - Safety Analysis Population (Part 2) Placebo - Safety Analysis Population (Part 1)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 38 (71.05%)
    33 / 60 (55.00%)
    21 / 33 (63.64%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    3 / 38 (7.89%)
    5 / 60 (8.33%)
    1 / 33 (3.03%)
         occurrences all number
    3
    5
    2
    Arteriovenous fistula site complication
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 60 (1.67%)
    0 / 33 (0.00%)
         occurrences all number
    2
    1
    0
    Arteriovenous fistula site haemorrhage
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 60 (1.67%)
    0 / 33 (0.00%)
         occurrences all number
    2
    1
    0
    Vascular access malfunction
         subjects affected / exposed
    0 / 38 (0.00%)
    2 / 60 (3.33%)
    2 / 33 (6.06%)
         occurrences all number
    0
    2
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 38 (0.00%)
    3 / 60 (5.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    3
    2
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 60 (1.67%)
    1 / 33 (3.03%)
         occurrences all number
    5
    1
    1
    Ventricular tachycardia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 60 (0.00%)
    3 / 33 (9.09%)
         occurrences all number
    3
    0
    5
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    2 / 38 (5.26%)
    3 / 60 (5.00%)
    2 / 33 (6.06%)
         occurrences all number
    2
    4
    2
    Pyrexia
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences all number
    2
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 38 (5.26%)
    2 / 60 (3.33%)
    0 / 33 (0.00%)
         occurrences all number
    2
    2
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 38 (5.26%)
    3 / 60 (5.00%)
    4 / 33 (12.12%)
         occurrences all number
    2
    3
    4
    Vomiting
         subjects affected / exposed
    5 / 38 (13.16%)
    2 / 60 (3.33%)
    1 / 33 (3.03%)
         occurrences all number
    6
    2
    1
    Diarrhoea
         subjects affected / exposed
    2 / 38 (5.26%)
    5 / 60 (8.33%)
    1 / 33 (3.03%)
         occurrences all number
    2
    5
    1
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 60 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    2
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    4 / 38 (10.53%)
    5 / 60 (8.33%)
    2 / 33 (6.06%)
         occurrences all number
    4
    5
    2
    Arthralgia
         subjects affected / exposed
    5 / 38 (13.16%)
    1 / 60 (1.67%)
    0 / 33 (0.00%)
         occurrences all number
    6
    1
    0
    Back pain
         subjects affected / exposed
    2 / 38 (5.26%)
    2 / 60 (3.33%)
    0 / 33 (0.00%)
         occurrences all number
    2
    2
    0
    Muscular weakness
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 60 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    2
    0
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 60 (1.67%)
    2 / 33 (6.06%)
         occurrences all number
    1
    1
    2
    Cellulitis
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 60 (0.00%)
    1 / 33 (3.03%)
         occurrences all number
    2
    0
    1
    Metabolism and nutrition disorders
    Calciphylaxis
         subjects affected / exposed
    8 / 38 (21.05%)
    4 / 60 (6.67%)
    8 / 33 (24.24%)
         occurrences all number
    9
    8
    9
    Decreased appetite
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 60 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    2
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 38 (2.63%)
    4 / 60 (6.67%)
    1 / 33 (3.03%)
         occurrences all number
    1
    4
    1
    Hypervolaemia
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 60 (1.67%)
    0 / 33 (0.00%)
         occurrences all number
    2
    1
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 60 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Sep 2019
    Protocol Amendment 1
    21 May 2021
    Protocol Amendment 2
    09 Dec 2021
    Protocol Amendment 3

    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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    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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