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    Clinical Trial Results:
    Response guided therapy with sofosbuvir and velpatasvir for 12 or 24 weeks in patients with genotype 3 chronic hepatitis C virus: is longer therapy worthwhile?

    Summary
    EudraCT number
    2016-000599-87
    Trial protocol
    GB  
    Global end of trial date
    04 Apr 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    29 Mar 2020
    First version publication date
    29 Mar 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    011094
    Additional study identifiers
    ISRCTN number
    ISRCTN16857338
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Queen Mary University of London
    Sponsor organisation address
    Joint Research Management Office, 5 Walden Street, Queen Mary Innovation Centre , London , United Kingdom, E1 2EF
    Public contact
    Dr Sally Burtles, Queen Mary University of London, 44 02078827260, sponsorsrep@bartshealth.nhs.uk
    Scientific contact
    Dr Sally Burtles, Queen Mary University of London, 44 02078827260, sponsorsrep@bartshealth.nhs.uk
    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
    26 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Apr 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    This trial will study the treatment effectiveness of sofosbuvir/velpatasvir for 12 or 24 weeks, in patients infected with genotype 3 hepatitis C virus (HCV), with advanced liver disease (cirrhosis), who are slow responders to treatment with persistent virus after the first two weeks of treatment. This trial will answer if identifying patients by their viral response during treatment (whether the virus is cleared after the first two weeks) can guide the duration of therapy required to achieve cure.
    Protection of trial subjects
    The main trial intervention is the allocation of different durations of the treatment sofosbuvir/velpatasvir to patients. Other trial procedures (such as blood tests and clinical examination) are in line with standard clinical practice. Regarding the drug treatment, the 12 week duration is standard of care while the 24 week duration is the test treatment. Available data has not shown any significant increase in adverse events in patients taking longer durations of treatment. For patients who have decompensated cirrhosis (that is, the most advanced stage of liver cirrhosis), the standard of care treatment is 12 weeks of sofosbuvir/ velpatasvir, plus an additional drug ribavirin, which has been shown to improve likelihood of viral cure. For this trial, patients with decompensated cirrhosis are invited to participate only if their clinicians deem them unsuitable for ribavirin use, since it is unclear if the trial treatment (12 or 24 weeks of sofosbuvir/velpatasvir without ribavirin)
    Background therapy
    Sofosbuvir/velpatsvir is a combined oral tablet of two medicines. The trial supply is purchased from the manufacturer Gilead. Sofosbuvir/velpatasvir is licensed in the EU for the treatment of all genotypes (subtypes) of chronic HCV infection. In most patients the licensed duration of treatment is 12 weeks. In genotype 3 HCV infection, which this trial investigates, the license recommendation is to consider the addition of ribavirin in patients with compensated cirrhosis, and to add ribavirin in patients with decompensated cirrhosis. This study investigates ribavirin-free treatments in genotype 3 HCV-infected patients, to reduce the side effect burden of therapy which is associated with ribavirin use. Sofosbuvir/velpatasvir is used in two durations - 12 weeks, which is considered the standard of care treatment, and 24 weeks, which is considered the test treatment. No other drugs or therapies are used within this trial.
    Evidence for comparator
    The comparator arm in this trial is the standard of care treatment for genotype 3 HCV infected patients, which is 12 weeks of sofosbuvir/velpatasvir. Given the evidence for the benefits of clearing HCV in patients with advanced liver disease, it is unethical to use placebo. The test treatment is 24 weeks of sofosbvuir/velpatasvir. This duration has been evaluated in a phase III trial showing no increased adverse events compared to the 12 week duration, but the 24 week regimen has not been recommended by license as it was not associated with significantly improved efficacy. However the study was not powered to detect significant differences in efficacy, and the 2016 international guidelines from EASL recommended that patients with genotype 3 HCV who have contraindications or poor tolerance to the use of ribaviirn should receive 24 weeks of sofosbuvir/velpatasvir alone.
    Actual start date of recruitment
    02 Jan 2017
    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
    United Kingdom: 25
    Worldwide total number of subjects
    25
    EEA total number of subjects
    25
    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)
    21
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The trial opened on 22 May 2017 and closed on 1 Oct 2018, following 2 extensions to the recruitment window. The trial also increased the number of sites from 5 to 6. The final recruit was 25 patients out of the intended 60.

    Pre-assignment
    Screening details
    The trial screened and recruited patients who exhibited a slow viral response after the first 2 weeks of sofosbuvir/velpatasvir treatment. Therefore all patients in whom clinicians preferred to add ribavirin were ineligible. The proportion of patients with slow viral response was roughly x. There were no screen failures.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded
    Blinding implementation details
    There was no blinding to the participant or investigator of the allocated trial intervention.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    12 weeks sofosbuvir/velpatasvir
    Arm description
    standard of care treatment arm
    Arm type
    Active comparator

    Investigational medicinal product name
    sofosbuvir/velpatasvir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet contains 400mg sofosbuvir and 100mg velpatasvir, taken orally 1 tablet per day with or without food.

    Arm title
    24 weeks sofosbuvir/velpatasvir
    Arm description
    The extended use of sofosbuvir/velpatasvir from week 13-24 is considered the investigational medicinal product (IMP). The product itself is the licensed, commercially available form.
    Arm type
    Experimental

    Investigational medicinal product name
    sofosbuvir/velpatasvir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet contains 400mg sofosbuvir and 100mg velpatasvir, taken orally 1 tablet per day with or without food.

    Number of subjects in period 1
    12 weeks sofosbuvir/velpatasvir 24 weeks sofosbuvir/velpatasvir
    Started
    12
    13
    Completed
    11
    11
    Not completed
    1
    2
         Adverse event, serious fatal
    -
    1
         Consent withdrawn by subject
    1
    -
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    12 weeks sofosbuvir/velpatasvir
    Reporting group description
    standard of care treatment arm

    Reporting group title
    24 weeks sofosbuvir/velpatasvir
    Reporting group description
    The extended use of sofosbuvir/velpatasvir from week 13-24 is considered the investigational medicinal product (IMP). The product itself is the licensed, commercially available form.

    Reporting group values
    12 weeks sofosbuvir/velpatasvir 24 weeks sofosbuvir/velpatasvir Total
    Number of subjects
    12 13 25
    Age categorical
    Adult patients aged >18 were eligible
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    9 12 21
        From 65-84 years
    3 1 4
        85 years and over
    0 0 0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    53.7 (30 to 84) 50.8 (31 to 78) -
    Gender categorical
    Units: Subjects
        Female
    7 6 13
        Male
    5 7 12
    Ethnicity
    self-reported ethnicity group
    Units: Subjects
        Caucasian
    3 5 8
        Asian
    8 8 16
        others/ mixed
    1 0 1
    HCV treatment history
    Units: Subjects
        treatment naive
    9 13 22
        peg-interferon/ribavirin
    2 0 2
        others
    1 0 1
    hepatic decompensation (past or current)
    Units: Subjects
        yes
    1 1 2
        no
    11 12 23
    HCV load
    Units: iu/mL
        arithmetic mean (full range (min-max))
    2977293 (12977 to 12882500) 2186396 (178000 to 5816224) -
    week 2 HCV load
    Units: iu/mL
        arithmetic mean (full range (min-max))
    170 (36 to 365) 58 (31 to 124) -
    Haemoglobin
    Units: g/L
        arithmetic mean (full range (min-max))
    131 (112 to 169) 137 (107 to 183) -
    platelet count
    Units: x10^9/L
        arithmetic mean (full range (min-max))
    148 (56 to 301) 176 (76 to 324) -
    sodium
    Units: mmol/L
        arithmetic mean (full range (min-max))
    140.3 (136 to 143) 139.1 (126 to 143) -
    creatinine
    Units: umol/L
        arithmetic mean (full range (min-max))
    62.4 (47 to 88) 72.2 (50 to 101) -
    alanine aminotransferase (ALT)
    Units: iu/L
        arithmetic mean (full range (min-max))
    92.2 (28 to 304) 109.7 (25 to 245) -
    bilirubin
    Units: umol/L
        arithmetic mean (full range (min-max))
    20.6 (7 to 82) 14.7 (3 to 32) -
    albumin
    Units: g/L
        arithmetic mean (full range (min-max))
    37.9 (31 to 46) 37.9 (29 to 51) -
    MELD
    Units: points
        arithmetic mean (full range (min-max))
    7.5 (6 to 16) 7.1 (6 to 11) -
    Subject analysis sets

    Subject analysis set title
    12 week sofosbuvir/velpatasvir (ITT)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This analysis set includes all patients recruited into the trial who randomised to the 12 week (control) treatment arm

    Subject analysis set title
    24 week sofosbuvir/velpatasvir (ITT)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This analysis set includes all patients recruited into the trial who randomised to the 24 week (test) treatment arm

    Subject analysis set title
    12 weeks sof/vel (mITT)
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    The mITT analysis population excluded patients without available primary endpoint (SVR12) data

    Subject analysis set title
    24 weeks sof/vel (mITT)
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    the mITT analysis population excluded patients without available primary endpoint (SVR12) data

    Subject analysis sets values
    12 week sofosbuvir/velpatasvir (ITT) 24 week sofosbuvir/velpatasvir (ITT) 12 weeks sof/vel (mITT) 24 weeks sof/vel (mITT)
    Number of subjects
    12
    13
    12
    11
    Age categorical
    Adult patients aged >18 were eligible
    Units: Subjects
        In utero
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
        Adults (18-64 years)
    9
    12
    9
    11
        From 65-84 years
    3
    1
    3
    0
        85 years and over
    0
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    53.7 (30 to 84)
    50.8 (31 to 78)
    53.7 (30 to 84)
    48.5 (31 to 59)
    Gender categorical
    Units: Subjects
        Female
    7
    6
        Male
    5
    7
    Ethnicity
    self-reported ethnicity group
    Units: Subjects
        Caucasian
    3
    5
        Asian
    8
    8
        others/ mixed
    1
    0
    HCV treatment history
    Units: Subjects
        treatment naive
    9
    13
        peg-interferon/ribavirin
    2
    0
        others
    1
    0
    hepatic decompensation (past or current)
    Units: Subjects
        yes
    1
    1
    1
    1
        no
    11
    12
    11
    10
    HCV load
    Units: iu/mL
        arithmetic mean (full range (min-max))
    2977293 (12977 to 12882500)
    2186396 (178000 to 5816224)
    week 2 HCV load
    Units: iu/mL
        arithmetic mean (full range (min-max))
    170 (36 to 365)
    58 (31 to 124)
    Haemoglobin
    Units: g/L
        arithmetic mean (full range (min-max))
    131 (112 to 169)
    137 (107 to 183)
    platelet count
    Units: x10^9/L
        arithmetic mean (full range (min-max))
    148 (56 to 301)
    176 (76 to 324)
    sodium
    Units: mmol/L
        arithmetic mean (full range (min-max))
    140.3 (136 to 143)
    139.1 (126 to 143)
    creatinine
    Units: umol/L
        arithmetic mean (full range (min-max))
    62.4 (47 to 88)
    72.2 (50 to 101)
    alanine aminotransferase (ALT)
    Units: iu/L
        arithmetic mean (full range (min-max))
    92.2 (28 to 304)
    109.7 (25 to 245)
    bilirubin
    Units: umol/L
        arithmetic mean (full range (min-max))
    20.6 (7 to 82)
    14.7 (3 to 32)
    albumin
    Units: g/L
        arithmetic mean (full range (min-max))
    37.9 (31 to 46)
    37.9 (29 to 51)
    MELD
    Units: points
        arithmetic mean (full range (min-max))
    7.5 (6 to 16)
    7.1 (6 to 11)

    End points

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    End points reporting groups
    Reporting group title
    12 weeks sofosbuvir/velpatasvir
    Reporting group description
    standard of care treatment arm

    Reporting group title
    24 weeks sofosbuvir/velpatasvir
    Reporting group description
    The extended use of sofosbuvir/velpatasvir from week 13-24 is considered the investigational medicinal product (IMP). The product itself is the licensed, commercially available form.

    Subject analysis set title
    12 week sofosbuvir/velpatasvir (ITT)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This analysis set includes all patients recruited into the trial who randomised to the 12 week (control) treatment arm

    Subject analysis set title
    24 week sofosbuvir/velpatasvir (ITT)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This analysis set includes all patients recruited into the trial who randomised to the 24 week (test) treatment arm

    Subject analysis set title
    12 weeks sof/vel (mITT)
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    The mITT analysis population excluded patients without available primary endpoint (SVR12) data

    Subject analysis set title
    24 weeks sof/vel (mITT)
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    the mITT analysis population excluded patients without available primary endpoint (SVR12) data

    Primary: proportion achieving SVR12 (undetectable HCV in serum at 12 weeks post treatment end)

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    End point title
    proportion achieving SVR12 (undetectable HCV in serum at 12 weeks post treatment end)
    End point description
    undetectable HCV is defined as RNA below limit of quantification up to 15iu/mL
    End point type
    Primary
    End point timeframe
    SVR outcome is collected from 12 weeks up to 16 weeks post treatment end.
    End point values
    12 weeks sofosbuvir/velpatasvir 24 weeks sofosbuvir/velpatasvir 12 week sofosbuvir/velpatasvir (ITT) 24 week sofosbuvir/velpatasvir (ITT) 12 weeks sof/vel (mITT) 24 weeks sof/vel (mITT)
    Number of subjects analysed
    12
    13
    12
    13
    12 [1]
    11 [2]
    Units: subjects
    number (not applicable)
        SVR12
    8
    11
    8
    11
    8
    11
        non-SVR12
    4
    2
    4
    2
    4
    11
    Attachments
    Untitled (Filename: treatment outcomes.png)
    Untitled (Filename: svr barcharts.png)
    Untitled (Filename: itt v mitt SVR.png)
    Notes
    [1] - one patient withdrew before study end after treatment failure (HCV relapse) was included
    [2] - 2 patients without primary endpoint data were excluded
    Statistical analysis title
    SVR12 - ITT
    Statistical analysis description
    proportion of patients achieving SVR12 between the 12 and 24 week treatment arms (all randomised patients analysed)
    Comparison groups
    12 week sofosbuvir/velpatasvir (ITT) v 24 week sofosbuvir/velpatasvir (ITT)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.05
    Method
    Fisher exact
    Parameter type
    Odds ratio (OR)
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -
         upper limit
    -
    Statistical analysis title
    SVR12 - mITT
    Statistical analysis description
    proportion of patients achieving SVR12 in both treatment arms (mITT - only patients with available SVR12 data included)
    Comparison groups
    12 week sofosbuvir/velpatasvir (ITT) v 24 week sofosbuvir/velpatasvir (ITT)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.05
    Method
    Fisher exact
    Parameter type
    Odds ratio (OR)
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -
         upper limit
    -

    Secondary: proportion of patients requiring treatment discontinuation

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    End point title
    proportion of patients requiring treatment discontinuation
    End point description
    End point type
    Secondary
    End point timeframe
    study start to end of planned treatment
    End point values
    12 weeks sofosbuvir/velpatasvir 24 weeks sofosbuvir/velpatasvir 12 week sofosbuvir/velpatasvir (ITT) 24 week sofosbuvir/velpatasvir (ITT)
    Number of subjects analysed
    12
    13
    12
    13
    Units: subjects
    number (not applicable)
        yes
    0
    0
    0
    0
        no
    12
    13
    12
    13
    No statistical analyses for this end point

    Secondary: proportion of patients with serious adverse events

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    End point title
    proportion of patients with serious adverse events
    End point description
    serious adverse events are defined as a medical event which results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect
    End point type
    Secondary
    End point timeframe
    study start to study end
    End point values
    12 weeks sofosbuvir/velpatasvir 24 weeks sofosbuvir/velpatasvir 12 week sofosbuvir/velpatasvir (ITT) 24 week sofosbuvir/velpatasvir (ITT)
    Number of subjects analysed
    12
    13
    12
    13
    Units: subjects
    number (not applicable)
        yes
    2
    3
    2
    3
        no
    10
    10
    10
    10
    Attachments
    Untitled (Filename: saes.png)
    Statistical analysis title
    proportion of patients with SAEs by treatment grow
    Comparison groups
    12 week sofosbuvir/velpatasvir (ITT) v 24 week sofosbuvir/velpatasvir (ITT)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.05
    Method
    Fisher exact
    Parameter type
    Odds ratio (OR)
    Confidence interval

    Secondary: quality of life - SF36 scores - physical component summary

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    End point title
    quality of life - SF36 scores - physical component summary
    End point description
    For each treatment arm, group mean scores at both timepoints, as well as the change from end of treatment to post treatment, will be analysed
    End point type
    Secondary
    End point timeframe
    the first survey timepoint is at the end of treatment (week 12 or 24 depending on treatment arm) and at 3 months post treatment end
    End point values
    12 weeks sofosbuvir/velpatasvir 24 weeks sofosbuvir/velpatasvir 12 weeks sof/vel (mITT) 24 weeks sof/vel (mITT)
    Number of subjects analysed
    11
    11
    11
    11
    Units: score
        end of treatment
    41
    50
    41
    50
        3 months post treatment
    36
    48
    36
    48
    No statistical analyses for this end point

    Secondary: quality of life - SF36 scores - mental component summary

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    End point title
    quality of life - SF36 scores - mental component summary
    End point description
    For each treatment arm, group mean scores at both timepoints, as well as the change from end of treatment to post treatment, will be analysed
    End point type
    Secondary
    End point timeframe
    the first survey timepoint is at the end of treatment (week 12 or 24 depending on treatment arm) and at 3 months post treatment end
    End point values
    12 weeks sofosbuvir/velpatasvir 24 weeks sofosbuvir/velpatasvir 12 weeks sof/vel (mITT) 24 weeks sof/vel (mITT)
    Number of subjects analysed
    11
    11
    11
    11
    Units: score
        end of treatment
    43
    44
    43
    44
        3 months post treatment end
    38
    47
    38
    47
    Attachments
    Sf36
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    start of sofosbuvir/velpatasivr treatment to end of follow up (3 months post treatment end). This trial recruits patients who have taken at least 2 weeks of treatment as standard of care. AEs which occurred before recruitment are retrospectively assessed.
    Adverse event reporting additional description
    Week 12-24 of sofosbuvir/velpatasvir is considered the investigational medicinal product (IMP) in this trial, therefore only AEs associated with IMP use (until the end of follow up) are reported to the MHRA.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    12 weeks sofosbuvir/velpatasvir (control arm)
    Reporting group description
    -

    Reporting group title
    24 weeks sofosbuvir/velpatasvir (test arm)
    Reporting group description
    -

    Serious adverse events
    12 weeks sofosbuvir/velpatasvir (control arm) 24 weeks sofosbuvir/velpatasvir (test arm)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 12 (16.67%)
    3 / 13 (23.08%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Deep vein thrombosis
    Additional description: distal femoral deep vein thrombosis (associated with cellulitis)
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
    Additional description: cause of death not established but not felt related to treatment given patient's age and comorbidities
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatobiliary disorders
    Hepatocellular carcinoma
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Removal of external fixation
    Additional description: removal of screws from left lower limb
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
    Additional description: left leg cellulitis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    12 weeks sofosbuvir/velpatasvir (control arm) 24 weeks sofosbuvir/velpatasvir (test arm)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 12 (75.00%)
    12 / 13 (92.31%)
    Immune system disorders
    Rhinitis allergic
    Additional description: hay fever
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Lethargy
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Fatigue
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Overdose
    Additional description: accidental overdose of study medication
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Upper respiratory tract infection
    Additional description: 2 patients from the test arm reported coryzal symptoms
         subjects affected / exposed
    0 / 12 (0.00%)
    5 / 13 (38.46%)
         occurrences all number
    0
    5
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Sinusitis
    Additional description: sinus infection
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 13 (15.38%)
         occurrences all number
    1
    2
    Nervous system disorders
    Headache
    Additional description: one patient on the test arm reported heaviness of head
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 13 (23.08%)
         occurrences all number
    0
    3
    Ear and labyrinth disorders
    Discharge
    Additional description: itchy & discharging middle ear
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Ear discomfort
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Dizziness
    Additional description: one participant on the standard of care arm reported light headedness
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Rectal haemorrhage
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    Vomiting
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    Haematemesis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Dyspepsia
    Additional description: bloating
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Abdominal pain
         subjects affected / exposed
    3 / 12 (25.00%)
    3 / 13 (23.08%)
         occurrences all number
    3
    3
    Hepatobiliary disorders
    Scan abdomen abnormal
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Urinary tract infection
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Pyuria
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Renal impairment
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Dermatitis allergic
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Pruritus
    Additional description: itchy skin
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 13 (15.38%)
         occurrences all number
    1
    2
    Gout
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Arthralgia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Pain in extremity
    Additional description: posterior lower leg pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Paresis
    Additional description: weakness of arms and legs
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Folate deficiency
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Iron deficiency
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Gynaecomastia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Eye infection
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 13 (7.69%)
         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
    24 Jul 2017
    change in research site (St Mary's Hospital, London to Royal Sussex County Hospital, Brighton) and addition of one extra site (North Manchester General Hospital) making a total of 6
    11 Dec 2017
    change in research site (Royal Sussex County Hospital, Brighton to Chelsea & Westminster Hospital, London)

    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.
    The trial was terminated early prior to reaching the recruitment target. The total recruit was 25 patients out of planned 60. The study showed improved SVR in the test arm compared stop standard of care but the study has limited power.
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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