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    Clinical Trial Results:
    Antelope: Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS)

    Summary
    EudraCT number
    		 2018-004751-20
    Trial protocol
    		 PL   HR  
    Global end of trial date
    23 Aug 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Mar 2022
    First version publication date
    29 Mar 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    PB006-03-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04115488
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Polpharma Biologics S.A.
    Sponsor organisation address
    ul. Trzy Lipy 3, Gdańsk, Poland, 80-172
    Public contact
    Karsten Roth, Director Clinical Research and Development, Polpharma Biologics S.A., +48 607 697 896, clinicaltrials@polpharmabiologics.com
    Scientific contact
    Karsten Roth, Director Clinical Research and Development, Polpharma Biologics S.A., +48 607 697 896, clinicaltrials@polpharmabiologics.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
    21 Oct 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Mar 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Aug 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluate and compare the cumulative number of new active lesions
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all subjects as required.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Jun 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 59
    Country: Number of subjects enrolled
    Croatia: 2
    Country: Number of subjects enrolled
    Belarus: 49
    Country: Number of subjects enrolled
    Moldova, Republic of: 2
    Country: Number of subjects enrolled
    Serbia: 24
    Country: Number of subjects enrolled
    Ukraine: 99
    Country: Number of subjects enrolled
    Georgia: 30
    Worldwide total number of subjects
    265
    EEA total number of subjects
    61
    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)
    265
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a Phase 3 multicenter, double-blind, active-controlled, randomized, parallel-group study to assess the similarity in efficacy, safety, and immunogenicity of biosimilar natalizumab PB006 compared to European Union-approved Tysabri in patients with Relapsing-remitting multiple sclerosis (RRMS).

    Pre-assignment
    Screening details
    		 All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PB006
    Arm description
    		 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of PB006 at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PB006
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of PB006 at a dose of 300 milligram (mg).

    Arm title
    		 Tysabri
    Arm description
    		 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. Patients re-randomized and switched from Tysabri to PB006 at Week 24 still received a total of 12 infusions (6 infusions of Tysabri and 6 infusions of PB006).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tysabri
    Investigational medicinal product code
    Other name
    natalizumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg).

    Investigational medicinal product name
    PB006
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of PB006 at a dose of 300 milligram (mg).

    Number of subjects in period 1 [1]
    		PB006 Tysabri
    Started
    131
    133
    Completed
    117
    122
    Not completed
    14
    11
         Adverse event, non-fatal
    8
    4
         Other than listed
    6
    7
    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: Out of the 265 enrolled subjects, 264 were randomized.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PB006
    Reporting group description
    		 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of PB006 at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions.

    Reporting group title
    Tysabri
    Reporting group description
    		 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. Patients re-randomized and switched from Tysabri to PB006 at Week 24 still received a total of 12 infusions (6 infusions of Tysabri and 6 infusions of PB006).

    Reporting group values
    		 PB006 Tysabri Total
    Number of subjects
    		 131 133 264
    Age categorical
    The Full Analysis Set (FAS) Population includes all patients who were randomized and have received at least one infusion of the study drug.
    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)
    		 131 133 264
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    The Full Analysis Set (FAS) Population includes all patients who were randomized and have received at least one infusion of the study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 36.8 ( 9.05 ) 9.73 ( 37.0 ) -
    Gender categorical
    The Full Analysis Set (FAS) Population includes all patients who were randomized and have received at least one infusion of the study drug.
    Units: Subjects
        Female
    		 84 78 162
        Male
    		 47 55 102
    Race (NIH/OMB)
    The Full Analysis Set (FAS) Population includes all patients who were randomized and have received at least one infusion of the study drug.
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Black or African American
    		 0 0 0
        Asian
    		 0 0 0
        White
    		 131 133 264
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Not reported
    		 0 0 0
        Other
    		 0 0 0
    Ethnicity (NIH/OMB)
    The Full Analysis Set (FAS) Population includes all patients who were randomized and have received at least one infusion of the study drug.
    Units: Subjects
        Hispanic or Latino
    		 0 0 0
        Not Hispanic or Latino
    		 131 133 264
        Not Reported
    		 0 0 0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    PB006
    Reporting group description
    		 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of PB006 at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions.

    Reporting group title
    Tysabri
    Reporting group description
    		 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. Patients re-randomized and switched from Tysabri to PB006 at Week 24 still received a total of 12 infusions (6 infusions of Tysabri and 6 infusions of PB006).

    Subject analysis set title
    PB006 (SSW)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of PB006 at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not.

    Subject analysis set title
    Tysabri Switched to PB006 at week 24 (SSW)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. Patients re-randomized and switched from Tysabri to PB006 at Week 24 still received a total of 12 infusions (6 infusions of Tysabri and 6 infusions of PB006). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not.

    Subject analysis set title
    Tysabri continued at week 24 (SSW)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not.

    Subject analysis set title
    PB006 (SAF)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of PB006 at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated.

    Subject analysis set title
    Tysabri Switched to PB006 at week 24 (SAF)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. Patients re-randomized and switched from Tysabri to PB006 at Week 24 still received a total of 12 infusions (6 infusions of Tysabri and 6 infusions of PB006). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated.

    Subject analysis set title
    Tysabri continued at week 24 (SAF)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated.

    Primary: Cumulative number of new active lesions over 24 weeks

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    End point title
    		 Cumulative number of new active lesions over 24 weeks
    End point description
    Cumulative number of new active lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. Per-Protocol Population (PP): patients who completed the 24-week treatment period without major protocol deviations that may have influenced the analysis of the primary endpoint and for whom sufficient post-baseline MRI data were available (incl baseline, Week 24 and at least 1/3 MRI visits). Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Primary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    126 [1]
    127 [2]
    122 [3]
    30 [4]
    95 [5]
    Units: lesions
        arithmetic mean (standard deviation)
    1.4 ( 3.73 )
    1.9 ( 3.97 )
    1.4 ( 3.65 )
    2.1 ( 3.78 )
    1.9 ( 4.09 )
    Notes
    [1] - PP
    [2] - PP
    [3] - SSW
    [4] - SSW
    [5] - SSW
    Statistical analysis title
    		 Primary Efficacy Analysis
    Statistical analysis description
    Data was analyzed using a negative binomial model with a logarithmic link function and fixed effects for the treatment group and stratification factors. Equivalence was tested based 95% confidence interval. Difference calculated as Tysabri minus PB006.
    Comparison groups
    PB006 v Tysabri
    Number of subjects included in analysis
    253
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    Parameter type
    		 Exponentiated Difference
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.613
         upper limit
    		 0.944
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.397

    Secondary: Cumulative number of new active lesions over 48 weeks

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    End point title
    		 Cumulative number of new active lesions over 48 weeks
    End point description
    Cumulative number of new active lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent was administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg]. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    122 [6]
    96 [7]
    119 [8]
    29 [9]
    95 [10]
    Units: Lesions
        arithmetic mean (standard deviation)
    1.5 ( 3.72 )
    2.3 ( 5.68 )
    1.5 ( 3.75 )
    2.1 ( 3.82 )
    2.3 ( 5.70 )
    Notes
    [6] - FAS
    [7] - FAS, patients who switch from Tysabri to PB006 are excluded.
    [8] - SSW
    [9] - SSW
    [10] - SSW
    No statistical analyses for this end point

    Secondary: Cumulative number of new GdE T1-weighted lesions over 24 weeks

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    End point title
    		 Cumulative number of new GdE T1-weighted lesions over 24 weeks
    End point description
    Cumulative number of new GdE T1-weighted lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg]. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    126 [11]
    127 [12]
    122 [13]
    30 [14]
    95 [15]
    Units: Lesions
        arithmetic mean (standard deviation)
    0.3 ( 1.01 )
    0.4 ( 1.25 )
    0.3 ( 1.02 )
    0.4 ( 0.81 )
    0.4 ( 1.37 )
    Notes
    [11] - FAS
    [12] - FAS
    [13] - FAS
    [14] - FAS
    [15] - FAS
    No statistical analyses for this end point

    Secondary: Cumulative number of new GdE T1-weighted lesions over 48 weeks

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    End point title
    		 Cumulative number of new GdE T1-weighted lesions over 48 weeks
    End point description
    Cumulative number of new GdE T1-weighted lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg]. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    122 [16]
    96 [17]
    119 [18]
    29 [19]
    95 [20]
    Units: Lesions
        arithmetic mean (standard deviation)
    0.3 ( 1.02 )
    0.4 ( 1.39 )
    0.3 ( 1.03 )
    0.4 ( 0.82 )
    0.4 ( 1.40 )
    Notes
    [16] - FAS
    [17] - FAS
    [18] - SSW
    [19] - SSW
    [20] - SSW
    No statistical analyses for this end point

    Secondary: Number of patients without new GdE T1-weighted lesions over 24 weeks

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    End point title
    		 Number of patients without new GdE T1-weighted lesions over 24 weeks
    End point description
    Number of patients without new GdE T1-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg]. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    131 [21]
    133 [22]
    122 [23]
    30 [24]
    95 [25]
    Units: Subjects
    109
    105
    105
    23
    80
    Notes
    [21] - FAS
    [22] - FAS
    [23] - SSW
    [24] - SSW
    [25] - SSW
    No statistical analyses for this end point

    Secondary: Number of patients without new GdE T1-weighted lesions over 48 weeks

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    End point title
    		 Number of patients without new GdE T1-weighted lesions over 48 weeks
    End point description
    Number of patients without new GdE T1-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg]. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    131 [26]
    103 [27]
    122 [28]
    30 [29]
    95 [30]
    Units: Subjects
    105
    80
    102
    22
    79
    Notes
    [26] - FAS
    [27] - FAS, patients who switch from Tysabri to PB006 are excluded.
    [28] - SSW
    [29] - SSW
    [30] - SSW
    No statistical analyses for this end point

    Secondary: Cumulative number of new/enlarging T2-weighted lesions over 24 weeks

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    End point title
    		 Cumulative number of new/enlarging T2-weighted lesions over 24 weeks
    End point description
    Cumulative number of new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    126 [31]
    127 [32]
    122 [33]
    30 [34]
    95 [35]
    Units: Lesions
        arithmetic mean (standard deviation)
    1.5 ( 3.79 )
    2.0 ( 4.12 )
    1.5 ( 3.83 )
    2.2 ( 3.84 )
    2.0 ( 4.25 )
    Notes
    [31] - FAS
    [32] - FAS
    [33] - SSW
    [34] - SSW
    [35] - SSW
    No statistical analyses for this end point

    Secondary: Cumulative number of new/enlarging T2-weighted lesions over 48 weeks

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    End point title
    		 Cumulative number of new/enlarging T2-weighted lesions over 48 weeks
    End point description
    Cumulative number of new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    122 [36]
    96 [37]
    119 [38]
    29 [39]
    95 [40]
    Units: Lesions
        arithmetic mean (standard deviation)
    1.6 ( 3.90 )
    2.4 ( 5.79 )
    1.6 ( 3.93 )
    2.2 ( 3.89 )
    2.5 ( 5.81 )
    Notes
    [36] - FAS
    [37] - FAS, patients who switch from Tysabri to PB006 are excluded.
    [38] - SSW
    [39] - SSW
    [40] - SSW
    No statistical analyses for this end point

    Secondary: Number of persistent lesions after 24 weeks

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    End point title
    		 Number of persistent lesions after 24 weeks
    End point description
    Number of persistent lesions after 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg]. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    126 [41]
    127 [42]
    122 [43]
    30 [44]
    95 [45]
    Units: Lesions
        arithmetic mean (standard deviation)
    0.5 ( 2.46 )
    0.4 ( 2.92 )
    0.5 ( 2.49 )
    0.1 ( 0.31 )
    0.6 ( 3.37 )
    Notes
    [41] - FAS
    [42] - FAS
    [43] - SSW
    [44] - SSW
    [45] - SSW
    No statistical analyses for this end point

    Secondary: Number of persistent lesions after 48 weeks

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    End point title
    		 Number of persistent lesions after 48 weeks
    End point description
    Number of persistent lesions after 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg]. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    122 [46]
    96 [47]
    119 [48]
    29 [49]
    95 [50]
    Units: Lesions
        arithmetic mean (standard deviation)
    0.5 ( 2.55 )
    0.6 ( 3.35 )
    0.5 ( 2.58 )
    0.1 ( 0.26 )
    0.6 ( 3.37 )
    Notes
    [46] - FAS
    [47] - FAS, patients who switch from Tysabri to PB006 are excluded.
    [48] - SSW
    [49] - SSW
    [50] - SSW
    No statistical analyses for this end point

    Secondary: Annualized relapse rate after 24 weeks

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    End point title
    		 Annualized relapse rate after 24 weeks
    End point description
    Annualized relapse rate after 24 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses per patient. B: Duration of follow-up time per patient, defined as: (last day of follow-up - day of randomization + 1) / 365.25. Relapses per patient-year: A/B. FAS: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. SSW: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not.
    End point type
    Secondary
    End point timeframe
    Up to 24 weeks.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    131 [51]
    133 [52]
    122 [53]
    30 [54]
    95 [55]
    Units: Relapses per patient-year
        number (not applicable)
    0.206
    0.152
    0.194
    0.143
    0.114
    Notes
    [51] - FAS
    [52] - FAS
    [53] - SSW
    [54] - SSW
    [55] - SSW
    No statistical analyses for this end point

    Secondary: Annualized relapse rate after 48 weeks

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    End point title
    		 Annualized relapse rate after 48 weeks
    End point description
    Annualized relapse rate after 48 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses per patient. B: Duration of follow-up time per patient, defined as: (last day of follow-up - day of randomization + 1) / 365.25. Relapses per patient-year: A/B. FAS: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. SSW: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    131 [56]
    103 [57]
    122 [58]
    30 [59]
    95 [60]
    Units: Relapses per patient-year
        number (not applicable)
    0.174
    0.133
    0.168
    0.146
    0.113
    Notes
    [56] - FAS
    [57] - FAS, patients who switch from Tysabri to PB006 are excluded.
    [58] - SSW
    [59] - SSW
    [60] - SSW
    No statistical analyses for this end point

    Secondary: Change from baseline in Expanded Disability Status Scale (EDSS) after 24 weeks

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    End point title
    		 Change from baseline in Expanded Disability Status Scale (EDSS) after 24 weeks
    End point description
    Change from baseline in Expanded Disability Status Scale (EDSS) after 24 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in multiple sclerosis (MS), is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus "other") are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists. After re-randomization, Week 24 is considered baseline. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and week 24.
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    122 [61]
    125 [62]
    Units: Score on scale
        arithmetic mean (standard deviation)
    -0.03 ( 0.211 )
    0.00 ( 0.354 )
    Notes
    [61] - FAS
    [62] - FAS
    No statistical analyses for this end point

    Secondary: Change from baseline in Expanded Disability Status Scale (EDSS) after 48 weeks

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    End point title
    		 Change from baseline in Expanded Disability Status Scale (EDSS) after 48 weeks
    End point description
    Change from baseline in Expanded Disability Status Scale (EDSS) after 48 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in MS, is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus "other") are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists. FAS population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. SSW Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    FAS: Baseline (week 0) and week 48. SSW: Baseline (week 24) and week 48.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    117 [63]
    93 [64]
    117 [65]
    29 [66]
    93 [67]
    Units: Score on scale
        arithmetic mean (standard deviation)
    -0.14 ( 0.536 )
    -0.05 ( 0.443 )
    -0.10 ( 0.498 )
    -0.03 ( 0.325 )
    -0.02 ( 0.312 )
    Notes
    [63] - FAS
    [64] - FAS, patients who switch from Tysabri to PB006 are excluded.
    [65] - SSW
    [66] - SSW
    [67] - SSW
    No statistical analyses for this end point

    Secondary: Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 24 weeks

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    End point title
    		 Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 24 weeks
    End point description
    Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 24 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to 24 weeks.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    122 [68]
    125 [69]
    122 [70]
    30 [71]
    95 [72]
    Units: Percentage of subjects
    number (not applicable)
        Persistently positive (confirmed)
    28.7
    27.2
    28.7
    43.3
    22.1
        Positive, confirmed
    30.3
    29.6
    30.3
    43.3
    25.3
    Notes
    [68] - SAF
    [69] - SAF
    [70] - SSW
    [71] - SSW
    [72] - SSW
    No statistical analyses for this end point

    Secondary: Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 48 weeks

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    End point title
    		 Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 48 weeks
    End point description
    Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 48 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    115 [73]
    121 [74]
    115 [75]
    28 [76]
    93 [77]
    Units: Percentage of subjects
    number (not applicable)
        Persistently positive (confirmed)
    10.4
    11.6
    10.4
    17.9
    9.7
        Positive, confirmed
    11.3
    11.6
    11.3
    17.9
    9.7
    Notes
    [73] - SAF
    [74] - SAF
    [75] - SSW
    [76] - SSW
    [77] - SSW
    No statistical analyses for this end point

    Secondary: Percentage of subjects with neutralizing antibodies after 24 weeks

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    End point title
    		 Percentage of subjects with neutralizing antibodies after 24 weeks
    End point description
    Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 24 weeks. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to 24 weeks.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    37 [78]
    37 [79]
    37 [80]
    13 [81]
    24 [82]
    Units: Percentage of subjects
    number (not applicable)
        Positive, confirmed
    67.6
    64.9
    67.6
    61.5
    66.7
    Notes
    [78] - SAF
    [79] - SAF
    [80] - SSW
    [81] - SSW
    [82] - SSW
    No statistical analyses for this end point

    Secondary: Percentage of subjects with neutralizing antibodies after 48 weeks

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    End point title
    		 Percentage of subjects with neutralizing antibodies after 48 weeks
    End point description
    Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 48 weeks. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    13 [83]
    14 [84]
    13 [85]
    5 [86]
    9 [87]
    Units: Percentage of subjects
    number (not applicable)
        Positive, confirmed
    61.5
    50.0
    61.5
    60.0
    44.4
    Notes
    [83] - SAF
    [84] - SAF
    [85] - SSW
    [86] - SSW
    [87] - SSW
    No statistical analyses for this end point

    Secondary: Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks

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    End point title
    		 Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks
    End point description
    Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated.
    End point type
    Secondary
    End point timeframe
    Up to week 24
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    131 [88]
    133 [89]
    Units: Subjects
        TEAE
    62
    64
        Treatment-emergent SAE
    1
    0
    Notes
    [88] - SAF
    [89] - SAF
    No statistical analyses for this end point

    Secondary: Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks

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    End point title
    		 Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks
    End point description
    Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks.
    End point values
    		 PB006 (SAF) Tysabri Switched to PB006 at week 24 (SAF) Tysabri continued at week 24 (SAF)
    Number of subjects analysed
    131 [90]
    30 [91]
    103 [92]
    Units: Subjects
        TEAE
    85
    22
    71
        Treatment-emergent SAE
    3
    0
    2
    Notes
    [90] - SAF
    [91] - SAF
    [92] - SAF
    No statistical analyses for this end point

    Secondary: Natalizumab trough concentration (Ctrough) over time, week 8

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    End point title
    		 Natalizumab trough concentration (Ctrough) over time, week 8
    End point description
    Natalizumab trough concentration (Ctrough) over time, week 8. Serum samples were collected prior to treatment. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 8
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    118 [93]
    125 [94]
    Units: Nanograms per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    26804.75 ( 12949.541 )
    25010.49 ( 12557.895 )
    Notes
    [93] - FAS
    [94] - FAS
    No statistical analyses for this end point

    Secondary: Natalizumab trough concentration (Ctrough) over time, week 16

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    End point title
    		 Natalizumab trough concentration (Ctrough) over time, week 16
    End point description
    Natalizumab trough concentration (Ctrough) over time, week 16. Serum samples were collected prior to treatment. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    117 [95]
    122 [96]
    Units: Nanograms per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    33872.92 ( 18151.190 )
    32543.28 ( 14636.925 )
    Notes
    [95] - FAS
    [96] - FAS
    No statistical analyses for this end point

    Secondary: Natalizumab trough concentration (Ctrough) over time, week 24

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    End point title
    		 Natalizumab trough concentration (Ctrough) over time, week 24
    End point description
    Natalizumab trough concentration (Ctrough) over time, week 24. Serum samples were collected prior to treatment. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    117 [97]
    121 [98]
    Units: Nanograms per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    36853.93 ( 15292.389 )
    35617.65 ( 16049.669 )
    Notes
    [97] - FAS
    [98] - FAS
    No statistical analyses for this end point

    Secondary: Natalizumab trough concentration (Ctrough) over time, week 32

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    End point title
    		 Natalizumab trough concentration (Ctrough) over time, week 32
    End point description
    Natalizumab trough concentration (Ctrough) over time, week 32. Serum samples were collected prior to treatment. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 32
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    115 [99]
    94 [100]
    Units: Nanograms per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    37450.04 ( 16877.010 )
    36865.81 ( 19756.050 )
    Notes
    [99] - FAS
    [100] - FAS, patients who switch from Tysabri to PB006 are excluded.
    No statistical analyses for this end point

    Secondary: Natalizumab trough concentration (Ctrough) over time, week 48

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    End point title
    		 Natalizumab trough concentration (Ctrough) over time, week 48
    End point description
    Natalizumab trough concentration (Ctrough) over time, week 48. Serum samples were collected prior to treatment. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    110 [101]
    91 [102]
    Units: Nanograms per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    39097.58 ( 16801.710 )
    38432.86 ( 16495.407 )
    Notes
    [101] - FAS
    [102] - FAS, patients who switch from Tysabri to PB006 are excluded.
    No statistical analyses for this end point

    Secondary: Number of patients without new/enlarging T2-weighted lesions over 24 weeks

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    End point title
    		 Number of patients without new/enlarging T2-weighted lesions over 24 weeks
    End point description
    Number of patients without new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not.
    End point type
    Secondary
    End point timeframe
    Week 0 (baseline), week 8, 16, 20 and 24.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    131 [103]
    133 [104]
    122 [105]
    30 [106]
    95 [107]
    Units: Subjects
    75
    72
    72
    18
    52
    Notes
    [103] - FAS
    [104] - FAS
    [105] - SSW
    [106] - SSW
    [107] - SSW
    No statistical analyses for this end point

    Secondary: Number of patients without new/enlarging T2-weighted lesions over 48 weeks

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    End point title
    		 Number of patients without new/enlarging T2-weighted lesions over 48 weeks
    End point description
    Number of patients without new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    131 [108]
    103 [109]
    122 [110]
    30 [111]
    95 [112]
    Units: Subjects
    71
    52
    69
    17
    51
    Notes
    [108] - FAS
    [109] - FAS, patients who switch from Tysabri to PB006 are excluded.
    [110] - SSW
    [111] - SSW
    [112] - SSW
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal clinical laboratory tests at week 24 and week 48

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    End point title
    		 Number of patients with abnormal clinical laboratory tests at week 24 and week 48
    End point description
    Number of patients with abnormal clinical laboratory tests at week 24 and 48. The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not.
    End point type
    Secondary
    End point timeframe
    At week 24 and week 48.
    End point values
    		 PB006 Tysabri PB006 (SSW) Tysabri Switched to PB006 at week 24 (SSW) Tysabri continued at week 24 (SSW)
    Number of subjects analysed
    131 [113]
    133 [114]
    122 [115]
    30 [116]
    95 [117]
    Units: Subjects
        Week 24
    116
    114
    116
    27
    87
        Week 48
    108
    88
    108
    26
    88
    Notes
    [113] - FAS
    [114] - FAS, patients who switch from Tysabri to PB006 are excluded at week 48.
    [115] - SSW
    [116] - SSW
    [117] - SSW
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal findings in physical examination at week 24 and week 48

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    End point title
    		 Number of patients with abnormal findings in physical examination at week 24 and week 48
    End point description
    Number of patients with abnormal findings in physical examination at week 24 and week 48. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
    End point type
    Secondary
    End point timeframe
    Week 24 and end of study (week 48).
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    131 [118]
    133 [119]
    Units: Subjects
        Week 24
    10
    12
        End of study (week 48)
    11
    10
    Notes
    [118] - SAF
    [119] - SAF
    No statistical analyses for this end point

    Secondary: Change from baseline in blood pressure at week 24

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    End point title
    		 Change from baseline in blood pressure at week 24
    End point description
    Change from baseline in diastolic and systolic blood Pressure at week 24. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    At baseline and week 24.
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    122 [120]
    125 [121]
    Units: Millimeter of mercury (mmHg)
    arithmetic mean (standard deviation)
        Diastolic Blood Pressure
    -2.2 ( 7.30 )
    -0.6 ( 7.35 )
        Systolic Blood Pressure
    -1.0 ( 9.76 )
    -1.5 ( 11.33 )
    Notes
    [120] - SAF
    [121] - SAF
    No statistical analyses for this end point

    Secondary: Change from baseline in blood pressure at week 48

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    End point title
    		 Change from baseline in blood pressure at week 48
    End point description
    Change from baseline in diastolic and systolic blood Pressure at week 48. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    At baseline and end of study (week 48).
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    117 [122]
    93 [123]
    Units: Millimeter of mercury (mmHg)
        arithmetic mean (standard deviation)
    -1.1 ( 8.84 )
    0.4 ( 8.54 )
    Notes
    [122] - SAF
    [123] - SAF, patients who switch from Tysabri to PB006 are excluded.
    No statistical analyses for this end point

    Secondary: Change from baseline in heart rate at week 24

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    End point title
    		 Change from baseline in heart rate at week 24
    End point description
    Change from baseline in heart rate at week 24. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    At baseline and week 24.
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    122 [124]
    125 [125]
    Units: beats/minute
        arithmetic mean (standard deviation)
    -0.4 ( 9.05 )
    -1.4 ( 9.10 )
    Notes
    [124] - SAF
    [125] - SAF
    No statistical analyses for this end point

    Secondary: Change from baseline in heart rate at week 48

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    End point title
    		 Change from baseline in heart rate at week 48
    End point description
    Change from baseline in heart rate at week 48. Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Only subjects with non-missing endpoints were included in the analysis.
    End point type
    Secondary
    End point timeframe
    At baseline and end of study (week 48).
    End point values
    		 PB006 Tysabri
    Number of subjects analysed
    117 [126]
    93 [127]
    Units: beats/minute
        arithmetic mean (standard deviation)
    0.2 ( 9.74 )
    -0.3 ( 9.52 )
    Notes
    [126] - SAF
    [127] - SAF, patients who switch from Tysabri to PB006 are excluded.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks.
    Adverse event reporting additional description
    Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23
    Reporting groups
    Reporting group title
    PB006
    Reporting group description
    		 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of PB006 at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. Included in this arm are subjects who switched from Tysabri to PB006 at week 24, covering the period from week 24 till the end of study (week 48).

    Reporting group title
    Tysabri
    Reporting group description
    		 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. Patients re-randomized and switched from Tysabri to PB006 at Week 24 still received a total of 12 infusions (6 infusions of Tysabri and 6 infusions of PB006). Included in this arm are subjects who switched from Tysabri to PB006 at week 24, covering the period from week 0 till week 24.

    Serious adverse events
    		 PB006 Tysabri
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 161 (1.86%)
    2 / 133 (1.50%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Tremor
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Nasal septum deviation
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (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
    Pain in extremity
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 PB006 Tysabri
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    100 / 161 (62.11%)
    93 / 133 (69.92%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Fibroadenoma of breast
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Haemangioma of spleen
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Blood pressure fluctuation
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Hypotension
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Thrombophlebitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    5 / 161 (3.11%)
    2 / 133 (1.50%)
         occurrences all number
    5
    2
    Fatigue
         subjects affected / exposed
    5 / 161 (3.11%)
    1 / 133 (0.75%)
         occurrences all number
    5
    1
    Pyrexia
         subjects affected / exposed
    1 / 161 (0.62%)
    4 / 133 (3.01%)
         occurrences all number
    1
    4
    Hyperthermia
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Feeling hot
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 133 (1.50%)
         occurrences all number
    1
    2
    Oedema peripheral
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Discomfort
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Infusion site pain
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Menorrhagia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Metrorrhagia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Organic erectile dysfunction
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    5 / 161 (3.11%)
    3 / 133 (2.26%)
         occurrences all number
    5
    3
    Rhinitis allergic
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Allergic sinusitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Asthma
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Catarrh
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Paranasal sinus mucosal hypertrophy
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    4 / 161 (2.48%)
    4 / 133 (3.01%)
         occurrences all number
    4
    4
    Insomnia
         subjects affected / exposed
    4 / 161 (2.48%)
    1 / 133 (0.75%)
         occurrences all number
    6
    1
    Sleep disorder
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Somatic symptom disorder
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    2 / 161 (1.24%)
    4 / 133 (3.01%)
         occurrences all number
    2
    4
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    2
    Blood pressure increased
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 133 (1.50%)
         occurrences all number
    1
    2
    C-reactive protein increased
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Bilirubin conjugated increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    2
    0
    Lymphocyte count increased
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    White blood cell count increased
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 133 (1.50%)
         occurrences all number
    0
    2
    Ankle fracture
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Ligament sprain
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Limb injury
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Muscle injury
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Scar
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Thermal burn
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    27 / 161 (16.77%)
    23 / 133 (17.29%)
         occurrences all number
    38
    52
    Dizziness
         subjects affected / exposed
    3 / 161 (1.86%)
    3 / 133 (2.26%)
         occurrences all number
    3
    4
    Hypoaesthesia
         subjects affected / exposed
    3 / 161 (1.86%)
    2 / 133 (1.50%)
         occurrences all number
    3
    2
    Paraesthesia
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Presyncope
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Tension headache
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    4
    3
    Burning sensation
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Dysgeusia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Head titubation
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Hyposmia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Multiple sclerosis relapse
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    2
    Muscle spasticity
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 161 (2.48%)
    0 / 133 (0.00%)
         occurrences all number
    4
    0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Lymphadenitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Lymphopenia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Neutropenia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Normocytic anaemia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Vertigo
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Ocular discomfort
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Visual impairment
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    3 / 161 (1.86%)
    5 / 133 (3.76%)
         occurrences all number
    3
    5
    Nausea
         subjects affected / exposed
    4 / 161 (2.48%)
    3 / 133 (2.26%)
         occurrences all number
    4
    3
    Constipation
         subjects affected / exposed
    2 / 161 (1.24%)
    3 / 133 (2.26%)
         occurrences all number
    2
    4
    Vomiting
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 133 (1.50%)
         occurrences all number
    0
    2
    Abdominal pain
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    2
    0
    Chronic gastritis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Dental caries
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    2
    Dyspepsia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Large intestine polyp
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Pancreatitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Biliary dyskinesia
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Alopecia
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Erythema
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Pruritus
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 133 (0.00%)
         occurrences all number
    2
    0
    Angioedema
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Idiopathic angioedema
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Petechiae
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Skin depigmentation
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Leukocyturia
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 133 (1.50%)
         occurrences all number
    0
    2
    Dysuria
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Haematuria
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Nephroptosis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Renal pain
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Urinary retention
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Urinary tract inflammation
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    7 / 161 (4.35%)
    4 / 133 (3.01%)
         occurrences all number
    7
    4
    Pain in extremity
         subjects affected / exposed
    2 / 161 (1.24%)
    3 / 133 (2.26%)
         occurrences all number
    2
    3
    Muscle spasms
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Myalgia
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Neck pain
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 133 (1.50%)
         occurrences all number
    2
    2
    Arthralgia
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 133 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 133 (1.50%)
         occurrences all number
    0
    2
    Arthritis reactive
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    2
    0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    14 / 161 (8.70%)
    13 / 133 (9.77%)
         occurrences all number
    19
    14
    COVID-19
         subjects affected / exposed
    14 / 161 (8.70%)
    10 / 133 (7.52%)
         occurrences all number
    14
    10
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 161 (1.24%)
    4 / 133 (3.01%)
         occurrences all number
    2
    4
    Pharyngitis
         subjects affected / exposed
    1 / 161 (0.62%)
    4 / 133 (3.01%)
         occurrences all number
    2
    5
    Respiratory tract infection
         subjects affected / exposed
    2 / 161 (1.24%)
    2 / 133 (1.50%)
         occurrences all number
    2
    2
    Urinary tract infection
         subjects affected / exposed
    2 / 161 (1.24%)
    2 / 133 (1.50%)
         occurrences all number
    2
    3
    Bronchitis
         subjects affected / exposed
    1 / 161 (0.62%)
    3 / 133 (2.26%)
         occurrences all number
    1
    4
    Cystitis
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Oral herpes
         subjects affected / exposed
    2 / 161 (1.24%)
    2 / 133 (1.50%)
         occurrences all number
    2
    2
    Pneumonia
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Rhinitis
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 133 (1.50%)
         occurrences all number
    1
    2
    Herpes simplex
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Respiratory tract infection viral
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 133 (0.75%)
         occurrences all number
    2
    1
    Sinusitis
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Vaginal infection
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Acute sinusitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Ear infection
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Furuncle
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Helicobacter gastritis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Herpes zoster
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Infected fistula
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    2
    Laryngitis
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Pyelonephritis acute
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Pyoderma streptococcal
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 133 (0.75%)
         occurrences all number
    1
    1
    Tinea versicolour
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Tonsillitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Tracheitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection enterococcal
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    2
    Hyperlipidaemia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 133 (0.75%)
         occurrences all number
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 133 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Sep 2019
    The section about Overall Study Design has been revised to show that serum samples for anti-drug antibody (ADA) formation testing will now be collected at 2 additional time points: 4 Weeks and 28 Weeks.
    05 Feb 2020
    The sections Secondary Objectives, Overall Study Design, Secondary Endpoints, Statistical Methods, Secondary endpoints and Planned Sample Size have been updated to include the new study design of switching a group of patients from Tysabri to PB006 at Week 24 to evaluate and compare the immunogenic profiles of those on Tysabri only with those who switched.
    15 Jul 2020
    In order to simplify Clinical Study Reporting, the analysis of the primary endpoint will now be conducted together with all secondary endpoints at the end of the study (at Visit 13, Week 48). The primary endpoint itself (at Visit 7, Week 24) is not changed. Most protocol changes in this amendment relate to this simplification

    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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