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    Clinical Trial Results:
    A Randomized, Double-blind, Parallel Group, Multicenter Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of SAIT101 versus MabThera® versus Rituxan® in Patients with Rheumatoid Arthritis (RA).

    Summary
    EudraCT number
    		 2014-005368-13
    Trial protocol
    		 DE   HU   ES   CZ   IT  
    Global end of trial date
    07 Nov 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Nov 2019
    First version publication date
    13 Nov 2019
    Other versions
    Summary report(s)
    		 AGB001 CSR Synopsis

    Trial information

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    Trial identification
    Sponsor protocol code
    AGB001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02819726
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Archigen Biotech Limited
    Sponsor organisation address
    1 Francis Crick Avenue, Cambridge, United Kingdom, CB2 0AA
    Public contact
    Medical Director, Archigen Biotech Limited, +44 2037495000, info@archigenbio.com
    Scientific contact
    Medical Director , Archigen Biotech Limited, +44 2037495000, info@archigenbio.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
    07 Nov 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Nov 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Nov 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to compare the pharmacokinetics (PK) of SAIT101 (proposed rituximab biosimilar) versus rituximab licensed in the European Union (MabThera®, brand name in EU) versus rituximab licensed in the United States (Rituxan®, brand name in US) in patients with RA.
    Protection of trial subjects
    The study was conducted in accordance with the protocol, the ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, and applicable laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 SAIT101 is a proposed biosimilar product of rituximab which is developed by ArchigenBiotech. SAIT101, as a proposed biosimilar of rituximab in pharmaceutical form, strength, and administration route, is expected to play an important role in the treatment of RA. The substitution of rituximab by SAIT101 is expected to provide similar efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, and immunogenicity in subjects with RA. The dose selected for this study is based on the clinically effective dose of rituximab. Rituximab was initially developed and was approved under the trade name Rituxan® by the United States Food and Drug Administration (USFDA) in 1997. Rituxan was co-developed and marketed in the United States of America (USA) under the brand name Rituxan. It is marketed outside the USA by Roche under the brand name MabThera®. Both Mabthera and Rituxan were used as comparators in this clinical study to explore the biosimilarity of SAIT101 in RA to these licenced products.
    Actual start date of recruitment
    11 Oct 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 57
    Country: Number of subjects enrolled
    Spain: 33
    Country: Number of subjects enrolled
    Bulgaria: 13
    Country: Number of subjects enrolled
    Czech Republic: 12
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Hungary: 7
    Country: Number of subjects enrolled
    Korea, Republic of: 14
    Country: Number of subjects enrolled
    United States: 28
    Country: Number of subjects enrolled
    Mexico: 69
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 7
    Country: Number of subjects enrolled
    India: 46
    Worldwide total number of subjects
    294
    EEA total number of subjects
    130
    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)
    222
    From 65 to 84 years
    72
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a global study conducted in 66 study centres. The first patient entered the study on 11 October 2019 and the date of the last patients last study visit was 07 November 2019.

    Pre-assignment
    Screening details
    		 All the screening assessments were performed within 30 days prior to randomization on Day 1 (visit 2, baseline). A total of 463 patients were screened for the study and 294 were randomised to study treatment (i.e. there were 169 screen failures).

    Period 1
    Period 1 title
    Part A
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor
    Blinding implementation details
    This was a double-blind study. Subjects, Investigators, the Joint Assessor, and other site personnel remained blinded throughout the entire study period except for the study Pharmacist or designee. The IXRS was used to manage randomization to the treatment groups in a blinded manner.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SAIT101
    Arm description
    		 1000 mg iv SAIT101 on Days 1 and 5 (Part A)
    Arm type
    		 Experimental

    Investigational medicinal product name
    SAIT101
    Investigational medicinal product code
    Other name
    Biosimilar rituxumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The selected dose of SAIT101 test product, 1000 mg (10 mg/mL) was as per the authorized dosing schedule and the dose administered during the conduct of this study was within the therapeutic range for the treatment or prevention of RA. The Day 1 infusion rate (on both week 0 and week 24) of SAIT101 was started at 50 mg/hour; after the first 30 minutes, it was escalated in 50 mg/hour incremented every 30 minutes, to a maximum of 400 mg/hour.

    Arm title
    		 MabThera
    Arm description
    		 1000 mg iv MabThera on Day 1 and 15 (Part B). 1000 mg iv Mabthera on Week 24 and 26 (Part B) for edible subjects.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Mabthera
    Investigational medicinal product code
    Other name
    Rituximab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on Week 24 and 26 for eligible subjects.

    Arm title
    		 Rituxan
    Arm description
    		 1000 mg iv Rituxan on Days 1 and 15 (Part A) and 1000 mg iv Rituxan on Weeks 24 and 26 (Part B) for eligible subjects.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Rituxan
    Investigational medicinal product code
    Other name
    Rutuximab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The comparator drugs Rituxan are approved by FDA and European Medicines Agency, respectively for the treatment of RA at dose of two 1000 mg infusions on Day 1 and Day 15. The Day 1 infusion rate (on both week 0 and week 24) of Rituxan was started at 50 mg/hour; after the first 30 minutes, it was escalated in 50 mg/hour incremented every 30 minutes, to a maximum of 400 mg/hour.

    Number of subjects in period 1
    		SAIT101 MabThera Rituxan
    Started
    98
    98
    98
    Completed
    92
    88
    87
    Not completed
    6
    10
    11
         Consent withdrawn by subject
    3
    5
    6
         Lost to follow-up
    -
    1
    -
         Protocol deviation
    3
    4
    5
    Period 2
    Period 2 title
    Part B
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor
    Blinding implementation details
    This was a double-blind study. Subjects, Investigators, the Joint Assessor, and other site personnel remained blinded throughout the entire study period except for the study Pharmacist or designee. The IXRS was used to manage randomization to the treatment groups in a blinded manner.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SAIT101
    Arm description
    		 1000 mg iv SAIT101 on Days 1 and 5 (Part A)
    Arm type
    		 Experimental

    Investigational medicinal product name
    SAIT101
    Investigational medicinal product code
    Other name
    Biosimilar rituxumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The selected dose of SAIT101 test product, 1000 mg (10 mg/mL) was as per the authorized dosing schedule and the dose administered during the conduct of this study was within the therapeutic range for the treatment or prevention of RA. The Day 1 infusion rate (on both week 0 and week 24) of SAIT101 was started at 50 mg/hour; after the first 30 minutes, it was escalated in 50 mg/hour incremented every 30 minutes, to a maximum of 400 mg/hour.

    Arm title
    		 MabThera
    Arm description
    		 1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv Mabthera on Week 24 and 26 (Part B) for edible subjects.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Mabthera
    Investigational medicinal product code
    Other name
    Rituxamab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on Week 24 and 26 for eligible subjects.

    Arm title
    		 Rituxan
    Arm description
    		 1000 mg iv Rituxan on Days 1 and 15 (Part A) and 1000 mg iv Rituxan on Weeks 24 and 26 (Part B) for eligible subjects.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Rituxan
    Investigational medicinal product code
    Other name
    Rutuximab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The comparator drugs Rituxan are approved by FDA and European Medicines Agency, respectively for the treatment of RA at dose of two 1000 mg infusions on Day 1 and Day 15. The Day 1 infusion rate (on both week 0 and week 24) of Rituxan was started at 50 mg/hour; after the first 30 minutes, it was escalated in 50 mg/hour incremented every 30 minutes, to a maximum of 400 mg/hour.

    Number of subjects in period 2 [1]
    		SAIT101 MabThera Rituxan
    Started
    73
    70
    98
    Completed
    69
    62
    87
    Not completed
    4
    8
    11
         Consent withdrawn by subject
    2
    3
    6
         Lost to follow-up
    1
    2
    -
         Protocol deviation
    1
    3
    5
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: SAIT101 Arm: 19 patients completing Part A were not eligible for Part B MabThera Arm: 19 patients completing Part A were not eligible for Part B Rituxan arm: 10 patients participating in Part A were not eligible for Part B

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    SAIT101
    Reporting group description
    		 1000 mg iv SAIT101 on Days 1 and 5 (Part A)

    Reporting group title
    MabThera
    Reporting group description
    		 1000 mg iv MabThera on Day 1 and 15 (Part B). 1000 mg iv Mabthera on Week 24 and 26 (Part B) for edible subjects.

    Reporting group title
    Rituxan
    Reporting group description
    		 1000 mg iv Rituxan on Days 1 and 15 (Part A) and 1000 mg iv Rituxan on Weeks 24 and 26 (Part B) for eligible subjects.

    Reporting group values
    		 SAIT101 MabThera Rituxan Total
    Number of subjects
    		 98 98 98 294
    Age categorical
    Units: Subjects
        Adults (18-60 years)
    		 76 75 71 222
        Adults (>60 years)
    		 22 23 27 72
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 50.9 ( 12.41 ) 52.5 ( 10.87 ) 52.1 ( 12.09 ) -
    Gender categorical
    Units: Subjects
        Female
    		 79 81 80 240
        Male
    		 19 17 18 54
    Race
    Units: Subjects
        American Indian or Alaskan Native
    		 24 20 21 65
        Asian
    		 18 19 24 61
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black of African American
    		 2 0 1 3
        White
    		 52 56 52 160
        More than one race
    		 2 3 0 5
        Unknown or not reported
    		 0 0 0 0
    Anti-drug Antibody (ADA) Status
    Units: Subjects
        ADA Positive
    		 2 1 4 7
        ADA Negative
    		 96 97 94 287
    Disease Duration
    Units: Years
        arithmetic mean (standard deviation)
    		 9.8 ( 6.73 ) 11.2 ( 7.72 ) 9.3 ( 7.10 ) -
    C-Reactive Protein (CRP)
    Units: mg/L
        arithmetic mean (standard deviation)
    		 19.5 ( 28.99 ) 15.3 ( 20.63 ) 16.2 ( 17.91 ) -
    Erythrocyte Sedimentation Rate (ESR)
    Units: mm/hr
        arithmetic mean (standard deviation)
    		 51.0 ( 26.58 ) 47.5 ( 22.87 ) 51.5 ( 23.35 ) -
    Swollen Joint Count (SJC66)
    Units: Number analysed
        arithmetic mean (standard deviation)
    		 15.2 ( 7.97 ) 15.2 ( 7.01 ) 13.0 ( 6.19 ) -
    Tender Joint Count (TJC68)
    Units: Tender Joint Count
        arithmetic mean (standard deviation)
    		 21.7 ( 11.08 ) 22.6 ( 13.66 ) 20.0 ( 10.84 ) -
    Patient Global Assessment Visual Analogue Scale (VAS) Score
    Units: mm
        arithmetic mean (standard deviation)
    		 68.9 ( 15.87 ) 67.6 ( 17.53 ) 70.8 ( 17.04 ) -
    Physicain Global Assessment VAS Score
    Units: mm
        arithmetic mean (standard deviation)
    		 71.0 ( 14.3 ) 69.4 ( 15.9 ) 69.8 ( 14.32 ) -
    Patient Pain Assessment VAS Score
    Units: mm
        arithmetic mean (standard deviation)
    		 67.0 ( 18.71 ) 68.8 ( 20.02 ) 70.7 ( 19.06 ) -
    Health Assessment questionnaire Disability Index (HAQ-DI)
    Units: Score
        arithmetic mean (standard deviation)
    		 1.7 ( 0.57 ) 1.7 ( 0.64 ) 1.6 ( 0.64 ) -
    Disease Activity Score (DAS-28-CRP)
    Disease activity score based on a 28-joint count-C-Reactive Protein (DAS-28-CRP)
    Units: Score
        median (standard deviation)
    		 5.28 ( 0.890 ) 5.29 ( 0.807 ) 5.17 ( 0.833 ) -
    Disease Activity Score (DAS-28-ESR)
    Disease activity score based on a 28-joint count - Erythrocyte Sedimentation Rate (DAS-28-ESR).
    Units: Score
        arithmetic mean (standard deviation)
    		 6.54 ( 0.844 ) 6.53 ( 0.781 ) 6.48 ( 0.758 ) -
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 162.6 ( 9.29 ) 161.3 ( 8.79 ) 163.3 ( 8.37 ) -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 73.0 ( 17.62 ) 71.9 ( 16.94 ) 71.6 ( 17.99 ) -
    Body Mass Index (BMI)
    Units: kg/m2
        arithmetic mean (standard deviation)
    		 27.5 ( 5.48 ) 27.5 ( 5.46 ) 26.7 ( 5.95 ) -

    End points

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    End points reporting groups
    Reporting group title
    SAIT101
    Reporting group description
    		 1000 mg iv SAIT101 on Days 1 and 5 (Part A)

    Reporting group title
    MabThera
    Reporting group description
    		 1000 mg iv MabThera on Day 1 and 15 (Part B). 1000 mg iv Mabthera on Week 24 and 26 (Part B) for edible subjects.

    Reporting group title
    Rituxan
    Reporting group description
    		 1000 mg iv Rituxan on Days 1 and 15 (Part A) and 1000 mg iv Rituxan on Weeks 24 and 26 (Part B) for eligible subjects.
    Reporting group title
    SAIT101
    Reporting group description
    		 1000 mg iv SAIT101 on Days 1 and 5 (Part A)

    Reporting group title
    MabThera
    Reporting group description
    		 1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv Mabthera on Week 24 and 26 (Part B) for edible subjects.

    Reporting group title
    Rituxan
    Reporting group description
    		 1000 mg iv Rituxan on Days 1 and 15 (Part A) and 1000 mg iv Rituxan on Weeks 24 and 26 (Part B) for eligible subjects.

    Primary: Area under the concentration time curve from Time 0 to the last quantifiable concentration (AUC0-t)

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    End point title
    		 Area under the concentration time curve from Time 0 to the last quantifiable concentration (AUC0-t)
    End point description
    End point type
    Primary
    End point timeframe
    Base line (time zero = pre-dose Day 1) to the time of the last quantifiable plasma concentration.
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    79
    70
    76
    Units: h*µg/mL
        geometric mean (geometric coefficient of variation)
    144500 ( 34.2 )
    151600 ( 33.2 )
    154600 ( 35.6 )
    Attachments
    		 Untitled (Filename: Primary PK Forest Plots (SAIT101 v MabThera).PNG)
    Untitled (Filename: Primary PK Forest Plots (SAIT101 v Rituxan).PNG)
    Untitled (Filename: Primary PK Forest Plots (MabThera v Rituxan).PNG)
    Statistical analysis title
    		 SAIT101:MabThera (AUC0-t)
    Statistical analysis description
    GLS Mean Ratio of AUC(0-t) SAIT101 vs MabThera. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    149
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [1]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    95.33
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 87.07
         upper limit
    		 104.37
    Notes
    [1] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 SAIT101:Rituxan (AUC0-t)
    Statistical analysis description
    GLS Mean Ration of AUC(0-t) SAIT101 vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    155
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [2]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    93.43
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 85.54
         upper limit
    		 102.15
    Notes
    [2] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 MabThera:Rituxan (AUC0-t)
    Statistical analysis description
    GLS Mean Ration of AUC(0-t) Mabthera vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
    Comparison groups
    MabThera v Rituxan
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [3]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    98.06
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 89.49
         upper limit
    		 107.45
    Notes
    [3] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.

    Primary: Area under the concentration time curve from Time 0 to the last quantifiable concentration (AUC0∞)

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    End point title
    		 Area under the concentration time curve from Time 0 to the last quantifiable concentration (AUC0∞)
    End point description
    End point type
    Primary
    End point timeframe
    Baseline (time zero = pre-dose Day 1) to infinity (∞).
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    91
    91
    Units: h*µg/mL
        geometric mean (geometric coefficient of variation)
    152300 ( 34.6 )
    161900 ( 32.2 )
    161300 ( 33.3 )
    Statistical analysis title
    		 SAIT101:MabThera (AUC0-∞)
    Statistical analysis description
    GLS Mean Ration of (AUC0-∞) SAIT101 vs MabThera. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [4]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    94.07
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 86.91
         upper limit
    		 101.81
    Notes
    [4] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 SAIT101:Rituxan (AUC0-∞)
    Statistical analysis description
    GLS Mean Ration of (AUC0-∞) SAIT101 vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [5]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    94.39
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 87.21
         upper limit
    		 102.16
    Notes
    [5] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 MabThera:Rituxan (AUC0-∞)
    Statistical analysis description
    GLS Mean Ration of (AUC0-∞) MabThera vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    MabThera v Rituxan
    Number of subjects included in analysis
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [6]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    100.35
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 92.68
         upper limit
    		 108.65
    Notes
    [6] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.

    Primary: Area under the concentration time curve from Time 0 to Dat 15 (AUC0-D15))

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    End point title
    		 Area under the concentration time curve from Time 0 to Dat 15 (AUC0-D15))
    End point description
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose, Day 1) to pre-dose Day 15 (Part A).
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    91
    88
    83
    Units: h*µg/mL
        geometric mean (geometric coefficient of variation)
    42950 ( 26.7 )
    44600 ( 25.6 )
    43540 ( 24.1 )
    Statistical analysis title
    		 SAIT101:MabThera (AUC0-D15)
    Statistical analysis description
    GLS Mean Ration of (AUC0-D15) SAIT101 vs MabThera. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    179
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [7]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    96.31
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 90.52
         upper limit
    		 102.46
    Notes
    [7] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 SAIT101:Rituxan (AUC0-D15)
    Statistical analysis description
    GLS Mean Ration of (AUC0-D15) SAIT101 vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    174
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [8]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    96.31
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 90.52
         upper limit
    		 102.46
    Notes
    [8] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 MabThera:Rituxan (AUC0-D15)
    Statistical analysis description
    GLS Mean Ration of (AUC0-D15) MabThera vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    MabThera v Rituxan
    Number of subjects included in analysis
    171
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [9]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    102.43
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 96.14
         upper limit
    		 109.14
    Notes
    [9] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.

    Primary: Maximum Plasma Concentration (Cmax) after Day 15 infusion

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    End point title
    		 Maximum Plasma Concentration (Cmax) after Day 15 infusion
    End point description
    End point type
    Primary
    End point timeframe
    Cmax value after Day 15 infusion (Dose 2)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    94
    93
    93
    Units: µg/mL
        geometric mean (geometric coefficient of variation)
    406.0 ( 28.3 )
    427.7 ( 28.3 )
    411.1 ( 24.5 )
    Statistical analysis title
    		 SAIT101:MabThera (Cmax)
    Statistical analysis description
    GLS Mean Ration of Cmax SAIT101 vs MabThera. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [10]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    94.93
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 89.03
         upper limit
    		 101.23
    Notes
    [10] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 SAIT101:Rituxan (Cmax)
    Statistical analysis description
    GLS Mean Ration of Cmax SAIT101 vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [11]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    94.93
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 89.03
         upper limit
    		 101.23
    Notes
    [11] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 MabThera:rituxan (Cmax)
    Statistical analysis description
    GLS Mean Ration of Cmax SAIT1MabThera vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    MabThera v Rituxan
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [12]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    104.03
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 97.54
         upper limit
    		 110.95
    Notes
    [12] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.

    Primary: Trough concentration (Ctrough) before the second infusion on Day 15

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    End point title
    		 Trough concentration (Ctrough) before the second infusion on Day 15
    End point description
    End point type
    Primary
    End point timeframe
    Immediately before the second infusion of treatment on Day 15 (dose 2).
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    83
    81
    77
    Units: µg/mL
        geometric mean (geometric coefficient of variation)
    60.35 ( 40.3 )
    67.75 ( 36.2 )
    58.84 ( 97.9 )
    Statistical analysis title
    		 SAIT101:MabThera (Ctrough)
    Statistical analysis description
    GLS Mean Ratio of Ctrough SAIT101 vs MabThera. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    164
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [13]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    89.08
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 77.2
         upper limit
    		 102.79
    Notes
    [13] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 SAIT101:Rituxan (Ctrough)
    Statistical analysis description
    GLS Mean Ratio of Ctrough SAIT101 vs MabThera. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [14]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    102.56
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 88.72
         upper limit
    		 118.56
    Notes
    [14] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.
    Statistical analysis title
    		 MabThera:Rituxan (Ctrough)
    Statistical analysis description
    GLS Mean Ratio of Ctrough MabThera vs Rituxan. The standard comparison of the log-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment.
    Comparison groups
    MabThera v Rituxan
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [15]
    Method
    Parameter type
    		 GLS Mean Ratio
    Point estimate
    115.13
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 99.51
         upper limit
    		 133.21
    Notes
    [15] - Standard acceptance limits for bioequivalence (80.00% to 125.00%) for the treatment comparisons.

    Primary: Change from Baseline in DAS28-CRP at Week 24

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    End point title
    		 Change from Baseline in DAS28-CRP at Week 24
    End point description
    Change from Baseline (Day 1) in the Disease Activity Score 28 C-reactive protein score (DAS28-CRP) at Week 24.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) to Week 24.
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    91
    87
    85
    Units: Score on a scale
        least squares mean (standard deviation)
    -0.991 ( 1.1735 )
    -0.832 ( 0.8483 )
    -0.861 ( 0.9488 )
    Statistical analysis title
    		 SAIT101:MabThera (DAS28-CRP)
    Statistical analysis description
    Change from Baseline in DAS28-CRP at Week 24 SAIT101 vs MabThera. Least square means and confidence intervals (CIs) were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    178
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [16]
    P-value
    		 = 0.2402
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.422
         upper limit
    		 0.106
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.134
    Notes
    [16] - The equivalence between 2 study treatments would be declared if the two-sided 95% CI of the difference in change from baseline in DAS28-CRP at week 24 in entirely contained within the equivalence margin of [-0.6,0.6].
    Statistical analysis title
    		 SAIT101:Rituxan (DAS28-CRP)
    Statistical analysis description
    Change from Baseline in DAS28-CRP at Week 24 SAIT101 vs Rituxan. Least square means and confidence intervals (CIs) were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    176
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [17]
    P-value
    		 = 0.1346
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.469
         upper limit
    		 0.063
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.135
    Notes
    [17] - The equivalence between 2 study treatments would be declared if the two-sided 95% CI of the difference in change from baseline in DAS28-CRP at week 24 in entirely contained within the equivalence margin of [-0.6,0.6].
    Statistical analysis title
    		 Mabthera:Rituxan (DAS28-CRP)
    Statistical analysis description
    Change from Baseline in DAS28-CRP at Week 24 MabThera vs Rituxan. Least square means and confidence intervals (CIs) were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    MabThera v Rituxan
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [18]
    P-value
    		 = 0.7429
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.314
         upper limit
    		 0.224
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.137
    Notes
    [18] - The equivalence between 2 study treatments would be declared if the two-sided 95% CI of the difference in change from baseline in DAS28-CRP at week 24 in entirely contained within the equivalence margin of [-0.6,0.6].

    Primary: Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52

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    End point title
    		 Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52
    End point description
    Efficacy endpoint: Clinical remission response (CRR) defined by the Simplified Disease Activity Index (SDAI) <3.3 at weeks 8, 16, 24, 36 and 52 (EOS).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) to Week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    92
    91
    Units: Score on a scale
    number (confidence interval 95%)
        CRR Week 8
    0 (0.00 to 3.97)
    0 (0.00 to 4.01)
    0 (0.00 to 4.05)
        CRR Week 16
    0 (0.00 to 4.01)
    1 (0.19 to 5.84)
    0 (0.00 to 4.05)
        CRR Week 24
    0 (0.00 to 4.09)
    1 (0.20 to 6.23)
    0 (0.00 to 4.37)
        CRR Week 36
    2 (0.61 to 7.74)
    0 (0.00 to 4.48)
    1 (0.21 to 6.51)
        CRR Week 52 (EOS)
    1 (0.19 to 5.90)
    2 (0.63 to 7.91)
    2 (0.64 to 8.09)
    Statistical analysis title
    		 SAIT101:MabThera CRR Week 52
    Statistical analysis description
    Clinical Remission Response at Week 52 (EOS) SAIT101 vs MabThera. Clinical remission is defined as score of Simplified Disease Activity Index (SDAI) smaller than 3.3. The 95% CIs for clinical remission rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.
    Comparison groups
    MabThera v SAIT101
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.9
         upper limit
    		 3.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.92
    Statistical analysis title
    		 SAIT101:Rituxan CRR Week 52
    Statistical analysis description
    Clinical Remission Response at Week 52 (EOS) SAIT101 vs Rituxan. Clinical remission is defined as score of Simplified Disease Activity Index (SDAI) smaller than 3.3. The 95% CIs for clinical remission rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.07
         upper limit
    		 3.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.95
    Statistical analysis title
    		 MabThera:Rituxan CRR Week 52
    Statistical analysis description
    Clinical Remission Response at Week 52 (EOS) MabThera vs Rituxan. Clinical remission is defined as score of Simplified Disease Activity Index (SDAI) smaller than 3.3. The 95% CIs for clinical remission rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    183
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.05
         upper limit
    		 5.83
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.27

    Secondary: Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24))

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    End point title
    		 Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24))
    End point description
    End point type
    Secondary
    End point timeframe
    Week 2 to Week 24
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    64
    61
    65
    Units: h*µg/mL
        geometric mean (geometric coefficient of variation)
    107300 ( 41.1 )
    109200 ( 40.0 )
    116000 ( 40.2 )
    No statistical analyses for this end point

    Secondary: Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12))

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    End point title
    		 Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12))
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose Day 1 (Baseline) to Pre-dose Week 12 (AUC(0-w12))
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    89
    92
    Units: h*µg/mL
        geometric mean (geometric coefficient of variation)
    148500 ( 33.1 )
    157400 ( 30.3 )
    155900 ( 33.1 )
    No statistical analyses for this end point

    Secondary: Maximum Plasma Concentration (Cmax) Dose 1

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    End point title
    		 Maximum Plasma Concentration (Cmax) Dose 1
    End point description
    End point type
    Secondary
    End point timeframe
    Cmax post-infusion on Day 15.
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    92
    91
    Units: Hours
        median (inter-quartile range (Q1-Q3))
    5.167 (3.00 to 6.50)
    5.167 (3.00 to 358.75)
    4.500 (3.00 to 6.75)
    Attachments
    		 Untitled (Filename: PK Scatterplots Cmax, D2 and Ctrough.PNG)
    No statistical analyses for this end point

    Secondary: Maximum Plasma Concentration (Tmax) Dose 2

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    End point title
    		 Maximum Plasma Concentration (Tmax) Dose 2
    End point description
    End point type
    Secondary
    End point timeframe
    Post-infusion Day 24.
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    94
    93
    93
    Units: hours
        median (inter-quartile range (Q1-Q3))
    4.167 (2.92 to 5.50)
    4.167 (0.00 to 48.08)
    4.250 (2.92 to 23.50)
    No statistical analyses for this end point

    Secondary: Apparent Terminal Rate Constant (λz)

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    End point title
    		 Apparent Terminal Rate Constant (λz)
    End point description
    End point type
    Secondary
    End point timeframe
    First Dosing Period (Part A)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    91
    92
    Units: Hours
        least squares mean (standard deviation)
    0.002358 ( 0.00061132 )
    0.002283 ( 0.00067311 )
    0.002240 ( 0.00059435 )
    No statistical analyses for this end point

    Secondary: Systemic Clearance (CL)

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    End point title
    		 Systemic Clearance (CL)
    End point description
    End point type
    Secondary
    End point timeframe
    First Dosing Period (Part A)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    91
    91
    Units: L/day
        geometric mean (geometric coefficient of variation)
    0.01314 ( 34.6 )
    0.01235 ( 29.0 )
    0.01240 ( 33.3 )
    No statistical analyses for this end point

    Secondary: Volume of Ditribution (VD)

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    End point title
    		 Volume of Ditribution (VD)
    End point description
    End point type
    Secondary
    End point timeframe
    First Dosing Period
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    91
    91
    Units: Litres
        geometric mean (geometric coefficient of variation)
    5.757 ( 28.0 )
    5.635 ( 23.6 )
    5.727 ( 22.9 )
    No statistical analyses for this end point

    Secondary: Terminal Half-Life (T1/2)

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    End point title
    		 Terminal Half-Life (T1/2)
    End point description
    End point type
    Secondary
    End point timeframe
    First Dosing Interval
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    91
    92
    Units: Hours
        geometric mean (geometric coefficient of variation)
    303.7 ( 26.1 )
    316.1 ( 29.0 )
    319.7 ( 26.2 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52

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    End point title
    		 Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52
    End point description
    Efficacy endpoint: Change from baseline (Day 1) in DAS28-CRP at weeks 8, 16, 36 and 52 (End of Study). DAS28-CRP was calculated using the following equation: [0.56*Square Root (SQRT) (tender 28 joint count)+0.28*SQRT(swollen 28 joint count)+0.36*ln(CRP+1)]*1.10+1.15.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 52 (End of study).
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    98
    97
    98
    Units: Score on a scale
    least squares mean (standard deviation)
        Day 1 (Baseline)
    5.281 ( 0.8899 )
    5.288 ( 0.8073 )
    5.170 ( 0.8326 )
        Week 8
    4.405 ( 1.0189 )
    4.324 ( 1.1132 )
    4.252 ( 1.1393 )
        Week 16
    4.001 ( 1.1116 )
    4.155 ( 0.9750 )
    4.100 ( 1.0044 )
        Week 24
    4.300 ( 1.0331 )
    4.463 ( 1.0648 )
    4.443 ( 0.9774 )
        Week 36
    3.552 ( 1.1452 )
    3.823 ( 0.9290 )
    3.716 ( 1.0684 )
        Week 52 (EOS)
    3.660 ( 1.2636 )
    3.754 ( 1.3037 )
    3.518 ( 1.1276 )
    Attachments
    		 Untitled (Filename: Change in Basaeline in DAS28-CRP.PNG)
    Statistical analysis title
    		 SAIT101:MabThera (Change in DAS28-CRP at Week 52)
    Statistical analysis description
    GLS Means Difference SAIT101 vs MabThera in DAS29-CRP score Day 1 to Week 52 (EOS). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and Baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6068
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.428
         upper limit
    		 0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.172
    Statistical analysis title
    		 SAIT101:Rituxan (Change in DAS28-CRP at Week 52)
    Statistical analysis description
    LS Means Difference SAIT101 vs Rituxan DAS29-CRP score Day 1 to Week 52 (EOS). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and Baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.599
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.249
         upper limit
    		 0.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.172
    Statistical analysis title
    		 Mabthera:Rituxan (Change in DAS28-CRP at Week 52)
    Statistical analysis description
    LS Means Difference MabThera vs Rituxan DAS29-CRP score Day 1 to Week 52 (EOS). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and Baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    MabThera v Rituxan
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3053
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.165
         upper limit
    		 0.532
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.175

    Secondary: American College of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52

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    End point title
    		 American College of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52
    End point description
    Efficacy endpoint: American College of Rheumatology (ACR) 20% response criteria (ACR20) response rates at weeks 8, 16, 24, 36 and 52
    End point type
    Secondary
    End point timeframe
    Week 8 to week 52 (End of Study)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    98
    93
    92
    Units: ACR20 Reponse Rate
    number (confidence interval 95%)
        Week 8
    39 (31.70 to 51.10)
    33 (26.51 to 45.61)
    44 (37.91 to 57.91)
        Week 16
    50 (43.18 to 62.95)
    54 (48.48 to 68.21)
    53 (47.98 to 67.84)
        Week 24
    36 (28.79 to 49.35)
    31 (26.37 to 46.11)
    34 (29.68 to 50.10)
        Week 36
    63 (59.87 to 78.49)
    47 (46.52 to 67.46)
    58 (58.00 to 78.69)
        Week 52 (EOS)
    60 (53.75 to 72.82)
    49 (44.18 to 64.34)
    59 (55.98 to 75.26)
    Attachments
    		 Untitled (Filename: ACR20 Repsonses (%).PNG)
    Statistical analysis title
    		 SAIT101:MabThera ACR20 Reponse Rate at Week 52
    Statistical analysis description
    ACR20 Response Rate difference at Week 52 (EOS) assessment SAIT101 vs MabThera. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    191
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Response Rate Difference
    Point estimate
    9.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.74
         upper limit
    		 23.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.22
    Statistical analysis title
    		 SAIT101:Rituxan ACR20 Reponse Rate at ...
    Statistical analysis description
    ACR20 Response Rate difference at Week 52 (EOS) assessment SAIT101 vs Rituxan. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    190
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Response Rate Difference
    Point estimate
    -2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.95
         upper limit
    		 11.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.05
    Statistical analysis title
    		 MabThera:Rituxan ACR20 Reponse Rate at ...
    Statistical analysis description
    ACR20 Response Rate difference at Week 52 (EOS) assessment MabThera vs Rituxan. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Response Rate Difference
    Point estimate
    -11.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.47
         upper limit
    		 2.45
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.26

    Secondary: American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52

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    End point title
    		 American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52
    End point description
    Efficacy endpoint: American Collage of Rheumatology 50% response criteria (ACR50) response rates and American Collage of Rheumatology 70% response criteria (ACR70) at weeks 8, 16, 24, 36 and 52.
    End point type
    Secondary
    End point timeframe
    Week 8 to week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    98
    98
    98
    Units: ACR20 Response Rate
    number (confidence interval 95%)
        ACR50 Week 8
    13 (8.17 to 22.02)
    11 (6.73 to 19.95)
    14 (9.29 to 23.94)
        ACR70 Week 8
    2 (0.58 to 7.35)
    2 (0.59 to 7.51)
    2 (0.60 to 7.58)
        ACR50 Week 16
    17 (11.61 to 27.07)
    16 (11.00 to 26.40)
    14 (9.39 to 24.18)
        ACR70 Week 16
    9 (5.12 to 17.20)
    4 (1.70 to 10.65)
    5 (2.37 to 12.22)
        ACR50 Week 24
    15 (10.14 to 25.17)
    8 (4.73 to 17.11)
    5 (2.51 to 12.90)
        ACR70 Week 24
    8 (4.47 to 16.23)
    2 (0.63 to 8.00)
    3 (1.19 to 9.76)
        ACR50 Week 36
    37 (31.51 to 51.44)
    19 (15.37 to 33.38)
    25 (21.31 to 40.69)
        ACR70 Week 36
    19 (13.95 to 30.63)
    6 (3.40 to 15.06)
    12 (8.47 to 23.59)
        ACR50 Week 52 (EOS)
    35 (28.14 to 47.33)
    25 (19.58 to 37.80)
    30 (24.74 to 44.02)
        ACR70 Week 52 (EOS)
    23 (16.89 to 34.05)
    13 (8.64 to 23.16)
    17 (12.28 to 28.48)
    Attachments
    		 Untitled (Filename: ACR50 Reponses (%).PNG)
    Untitled (Filename: ACR70 Responses (%).PNG)
    Statistical analysis title
    		 SAIT101:MabThera (ACR50) Reponse Rate at Week 52
    Statistical analysis description
    ACR50 Response Rate Difference SAIT101 vs MabThera at Week 52 (EOS). The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Response Rate Difference
    Point estimate
    9.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.07
         upper limit
    		 22.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.87
    Statistical analysis title
    		 SAIT101:Rituxan (ACR50) Reponse Rate at Week 52
    Statistical analysis description
    ACR50 Response Rate Difference SAIT101 vs Rituxan at Week 52 (EOS). The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Response Rate Difference
    Point estimate
    3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.22
         upper limit
    		 17.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.07
    Statistical analysis title
    		 MabThera:Rituxan (ACR70) Reponse Rate at Week 52
    Statistical analysis description
    ACR70 Response Rate Difference MabThera vs Rituxan at Week 52 (EOS). The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Response Rate Difference
    Point estimate
    -4.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.68
         upper limit
    		 6.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.58
    Statistical analysis title
    		 SAIT101:MabThera (ACR70) Reponse Rate at Week 52
    Statistical analysis description
    ACR70 Response Rate Difference SAIT101 vs MabThera at Week 52 (EOS). The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Response Rate Difference
    Point estimate
    10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.52
         upper limit
    		 21.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.78
    Statistical analysis title
    		 SAIT101:Rituxan (ACR70) Reponse Rate at Week 52
    Statistical analysis description
    ACR70 Response Rate Difference SAIT101 vs Rituxan at Week 52 (EOS). The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Response Rate Difference
    Point estimate
    5.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.69
         upper limit
    		 17.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.08

    Secondary: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System)

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    End point title
    		 Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System)
    End point description
    Efficacy endpoint: Individual components of the ACR improvement criteria on Day 1 and at weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and tender joint count (TJC) (the 66/68 joint count system). SJC and TJC assess the level of skeletal disease involvement. the 66/68 Joint Count evaluates 66 joints for swelling and 68 joints for tenderness.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 to Week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    98
    97
    98
    Units: Swollen Joint Count
    least squares mean (standard deviation)
        Swollen Joint Count Day 1
    15.2 ( 7.97 )
    15.2 ( 15.2 )
    13.0 ( 6.19 )
        Swollen Joint Count Week 8
    8.6 ( 7.11 )
    8.4 ( 6.62 )
    7.7 ( 5.92 )
        Swollen Joint Count Week 16
    6.5 ( 4.86 )
    7.8 ( 7.20 )
    7.0 ( 5.37 )
        Swollen Joint Count Week 24
    8.5 ( 5.13 )
    10.0 ( 5.85 )
    10.0 ( 6.19 )
        Swollen Joint Count Week 36
    4.8 ( 6.21 )
    5.4 ( 5.72 )
    5.7 ( 5.49 )
        Swollen Joint Count Week 52 (EOS)
    5.2 ( 6.53 )
    6.5 ( 9.46 )
    4.6 ( 5.04 )
        Tender Joint Count Day 1
    21.7 ( 11.08 )
    22.6 ( 13.66 )
    20.0 ( 10.84 )
        Tender Count Count Week 8
    13.9 ( 9.94 )
    14.0 ( 9.94 )
    13.5 ( 10.69 )
        Tender Count Count Week 16
    11.1 ( 10.24 )
    12.5 ( 8.36 )
    11.8 ( 9.09 )
        Tender Count Count Week 24
    13.6 ( 9.79 )
    15.6 ( 11.94 )
    15.2 ( 11.62 )
        Tender Count Count Week 36
    8.3 ( 9.10 )
    10.9 ( 10.68 )
    9.6 ( 10.81 )
        Tender Count Count Week 52 (EOS)
    9.3 ( 9.34 )
    11.9 ( 15.18 )
    9.4 ( 11.41 )
    Statistical analysis title
    		 SAIT101:MabThera Swollen Joint Count (Week 52)
    Statistical analysis description
    Swollen Joint Count (SJC) Week 52 (EOS) assessment SAIT101 vs MabThera. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1997
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -1.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.23
         upper limit
    		 0.671
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.991
    Statistical analysis title
    		 SAIT101:Rituxan Swollen Joint Count (Week 52)
    Statistical analysis description
    Swollen Joint Count (SJC) Week 52 (EOS) assessment SAIT101 vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9098
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.074
         upper limit
    		 1.848
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.996
    Statistical analysis title
    		 MabThera:Rituxan Swollen Joint Count (Week 52)
    Statistical analysis description
    Swollen Joint Count (SJC) Week 52 (EOS) assessment MabThera vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.248
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.817
         upper limit
    		 3.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.008
    Statistical analysis title
    		 SAIT101:MabThera Tender Joint Count (Week 52)
    Statistical analysis description
    Tender Joint Count (TJC) Week 52 (EOS) assessment SAIT101 vs MabThera. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1931
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -1.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.909
         upper limit
    		 0.996
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.5
    Statistical analysis title
    		 SAIT101:Rituxan Tender Joint Count (Week 52)
    Statistical analysis description
    Tender Joint Count (TJC) Week 52 (EOS) assessment SAIT101 vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6068
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.722
         upper limit
    		 2.184
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.5
    Statistical analysis title
    		 Mabthera:Rituxan Tender Joint Count (Week 52)
    Statistical analysis description
    Tender Joint Count (TJC) Week 52 (EOS) assessment MabThera vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4352
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.805
         upper limit
    		 4.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.52

    Secondary: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS])

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    End point title
    		 Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS])
    End point description
    Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians global assessment of disease activity (assessed on 1 to 100 mm Visual Analog Scale [VAS]). Where 0 = no disease activity and 100 = maximum disease activity.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    97
    97
    98
    Units: Score on a scale
    least squares mean (standard error)
        Disease Activity Day 1
    71.0 ( 14.30 )
    69.4 ( 15.00 )
    69.8 ( 14.32 )
        Disease Activity Week 8
    45.6 ( 20.75 )
    43.2 ( 23.86 )
    44.6 ( 23.28 )
        Disease Activity Week 16
    39.2 ( 20.94 )
    39.0 ( 20.97 )
    42.3 ( 20.89 )
        Disease Activity Week 24
    47.9 ( 22.28 )
    47.8 ( 20.25 )
    49.0 ( 22.45 )
        Disease Activity Week 36
    30.3 ( 21.56 )
    36.3 ( 21.71 )
    31.4 ( 20.69 )
        Disease Activity Week 52 (EOS)
    31.1 ( 21.67 )
    35.1 ( 23.49 )
    31.2 ( 22.95 )
    Statistical analysis title
    		 SAIT101:MabThera Disease Activity (Week 52)
    Statistical analysis description
    Week 52 (EOS) Physician's Disease Activity Assessment SAIT101 vs MabThera. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2008
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -4.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.541
         upper limit
    		 2.226
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.242
    Statistical analysis title
    		 SAIT101:Rituxan Disease Activity (Week 52)
    Statistical analysis description
    Week 52 (EOS) Physician's Disease Activity Assessment SAIT101 vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9047
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.771
         upper limit
    		 5.994
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.242
    Statistical analysis title
    		 Mabthera:Rituxan Disease Activity (Week 52)
    Statistical analysis description
    Week 52 (EOS) Physician's Disease Activity Assessment MabThera vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2498
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    3.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.665
         upper limit
    		 10.204
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.268

    Secondary: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS])

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    End point title
    		 Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS])
    End point description
    Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 (Baseline) and at Weeks 8, 16, 24, 36 and 52 (EOS): Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS])
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 52
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    98
    98
    97
    Units: Score on a scale
    least squares mean (standard deviation)
        Assessment of Pain Day 1
    67.0 ( 18.71 )
    68.8 ( 20.02 )
    68.8 ( 19.27 )
        Assessment of Pain Week 8
    48.4 ( 22.79 )
    50.4 ( 22.40 )
    47.9 ( 23.03 )
        Assessment of Pain Week 16
    42.7 ( 23.34 )
    44.6 ( 20.91 )
    44.4 ( 22.91 )
        Assessment of Pain Week 24
    49.3 ( 24.15 )
    51.6 ( 21.44 )
    51.8 ( 23.58 )
        Assessment of Pain Week 36
    36.8 ( 24.56 )
    44.9 ( 23.78 )
    41.6 ( 23.46 )
        Assessment of Pain Week 52 (EOS)
    41.2 ( 24.34 )
    43.2 ( 24.42 )
    44.5 ( 26.10 )
    Statistical analysis title
    		 SAIT101:MabThera Assessment of Pain (Week 52)
    Statistical analysis description
    Patients Assessment of Pain Week 52 (EOS) SAIT101 vs MabThera. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other [19]
    P-value
    		 = 0.7322
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.0302
         upper limit
    		 5.841
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.592
    Notes
    [19] - Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 (Baseline) and at Weeks 8, 16, 24, 36 and 52 (EOS): Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS])
    Statistical analysis title
    		 SAIT101:Rituxan Assessment of Pain (Week 52)
    Statistical analysis description
    Patients Assessment of Pain Week 52 (EOS) SAIT101 vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other [20]
    P-value
    		 = 0.5418
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -2.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.347
         upper limit
    		 4.92
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.623
    Notes
    [20] - Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 (Baseline) and at Weeks 8, 16, 24, 36 and 52 (EOS): Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS])
    Statistical analysis title
    		 MabThera:Rituxan Assessment of Pain (Week 52)
    Statistical analysis description
    Patients Assessment of Pain Week 52 (EOS) MabThera vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other [21]
    P-value
    		 = 0.7869
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.136
         upper limit
    		 6.169
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.633
    Notes
    [21] - Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 (Baseline) and at Weeks 8, 16, 24, 36 and 52 (EOS): Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS])

    Secondary: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS)

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    End point title
    		 Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS)
    End point description
    Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants global assessment of disease activity (assessed on 1 to 100 mm VAS). Patients rate how their Rheumatoid Arthritis has affected them, where 0 = very well and 100 = very poor.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    97
    97
    97
    Units: Score on a scale
    least squares mean (standard deviation)
        Disease Activity Day 1
    68.9 ( 15.87 )
    67.6 ( 17.53 )
    70.8 ( 17.04 )
        Disease Activity Week 8
    46.9 ( 22.57 )
    49.1 ( 22.98 )
    48.5 ( 22.93 )
        Disease Activity Week 16
    43.9 ( 21.47 )
    44.4 ( 21.63 )
    44.2 ( 22.82 )
        Disease Activity Week 24
    50.8 ( 21.16 )
    51.1 ( 20.49 )
    53.1 ( 21.90 )
        Disease Activity Week 36
    35.7 ( 22.63 )
    42.7 ( 22.54 )
    42.5 ( 23.70 )
        Disease Activity Week 52 (EOS)
    41.4 ( 23.02 )
    42.4 ( 24.10 )
    43.1 ( 23.93 )
    Statistical analysis title
    		 SAIT101:MabThera Disease Activty (Week 52)
    Statistical analysis description
    Week 52 (EOS) Participants Disease Activity Assessment SAIT101 vs MabThera. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7097
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -1.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.062
         upper limit
    		 5.496
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.443
    Statistical analysis title
    		 SAIT101:Rituxan Disease Activty (Week 52)
    Statistical analysis description
    Week 52 (EOS) Participants Disease Activity Assessment SAIT101 vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6683
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.28
         upper limit
    		 5.317
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.453
    Statistical analysis title
    		 MabThera:Rituxan Disease Activty (Week 52)
    Statistical analysis description
    Week 52 (EOS) Participants Disease Activity Assessment MabThera vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9548
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.078
         upper limit
    		 6.682
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.494

    Secondary: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI])

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    End point title
    		 Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI])
    End point description
    Efficacy analysis: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants assessment of disability (Health Assessment Questionnaire-Disability Index [HAQ-DI 0-3]). The HAQ-DI questionnaire assesses the participants ability to function in daily life (8 categories) plus a pain VAS ranging from 0 (no pain) to 100 (Severe pain).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to week 52.
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    98
    98
    97
    Units: Score on a scale
    least squares mean (standard deviation)
        HAQ-DI Day 1
    1.610 ( 0.5728 )
    1.605 ( 670.65 )
    1.585 ( 0.6421 )
        HAQ-DI Week 8
    1.168 ( 0.6318 )
    1.314 ( 0.6919 )
    1.176 ( 0.6398 )
        HAQ-DI Week 16
    1.129 ( 0.5775 )
    1.246 ( 0.9463 )
    1.152 ( 0.6668 )
        HAQ-DI Week 24
    1.209 ( 0.6071 )
    1.335 ( 0.6382 )
    1.294 ( 0.6594 )
        HAQ-DI Week 36
    0.994 ( 0.6220 )
    1.182 ( 0.6883 )
    1.061 ( 0.6247 )
        HAQ-DI Week 52 (EOS)
    1.027 ( 0.6208 )
    1.207 ( 0.7025 )
    1.190 ( 0.7116 )
    Statistical analysis title
    		 SAIT101:MabThera HAQ-DI (Week 52)
    Statistical analysis description
    Week 52 (EOS) HAQ-DI score (0-3) SAIT101 vs MabThera. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0505
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.339
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.086
    Statistical analysis title
    		 SAIT101:Rituxan HAQ-DI (Week 52)
    Statistical analysis description
    Week 52 (EOS) HAQ-DI score (0-3) SAIT101 vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1141
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3079
         upper limit
    		 0.033
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.086
    Statistical analysis title
    		 MabThera:Rituxan HAQ-DI (Week 52)
    Statistical analysis description
    Week 52 (EOS) HAQ-DI score (0-3) MabThera vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7111
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.139
         upper limit
    		 0.204
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.087

    Secondary: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level

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    End point title
    		 Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level
    End point description
    Efficacy analysis: Individual Components of the ACR Improvement Criteria on Day 1 (Baseline) and at Weeks 8, 16, 24, 36 and 52 (EOS): C-reactive protein (CRP) level
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to week 52
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    98
    98
    98
    Units: Score on a scale
    least squares mean (standard deviation)
        CRP Day 1
    19.5 ( 28.99 )
    15.3 ( 20.63 )
    16.2 ( 17.91 )
        CRP Week 8
    12.5 ( 15.78 )
    12.3 ( 20.29 )
    10.4 ( 12.78 )
        CRP Week 16
    8.5 ( 11.78 )
    7.2 ( 9.02 )
    7.3 ( 6.90 )
        CRP Week 24
    9.5 ( 14.54 )
    8.3 ( 14.40 )
    7.9 ( 10.35 )
        CRP Week 36
    8.0 ( 20.33 )
    7.0 ( 10.38 )
    7.1 ( 9.72 )
        CRP Week 52 (EOS)
    9.8 ( 14.14 )
    9.1 ( 14.93 )
    7.4 ( 11.34 )
    Statistical analysis title
    		 SAIT101:MabThera CRP level Week 52
    Statistical analysis description
    Week 52 (EOS) C-Reactive Protein Sait101 vs MabThera. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8183
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.113
         upper limit
    		 3.253
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.871
    Statistical analysis title
    		 SAIT101:MabThera CRP level Week 52
    Statistical analysis description
    Week 52 (EOS) C-Reactive Protein Sait101 vs MabThera. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    SAIT101 v Rituxan v MabThera
    Number of subjects included in analysis
    294
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8183
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.113
         upper limit
    		 3.253
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.871
    Statistical analysis title
    		 SAIT101:Rituxan CRP level Week 52
    Statistical analysis description
    Week 52 (EOS) C-Reactive Protein Sait101 vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4186
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.164
         upper limit
    		 5.191
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.868
    Statistical analysis title
    		 MabThera:Rituxan CRP level Week 52
    Statistical analysis description
    Week 52 (EOS) C-Reactive Protein MabThera vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3035
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Difference
    Point estimate
    1.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.768
         upper limit
    		 5.655
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.885

    Secondary: Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52

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    End point title
    		 Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52
    End point description
    Efficacy endpoint: Change from baseline (Day 1) in DAS28-erythrocyte sedimentation rate (ESR) at weeks 8, 16, 24, 36 and 52 (EOS). DAS28-ESR was calculated using the following equation: [0.56*SQRT(tender 28 joint count)+0.28*SQRT(swollen 28 joint count)+0.7*ln(ESR)]+0.014*patient global health assessment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    96
    96
    96
    Units: Score on scale
    least squares mean (standard deviation)
        DAS28-ESR Day 1
    6.537 ( 0.8440 )
    6.533 ( 0.7810 )
    6.480 ( 0.7577 )
        DAS28-ESR Week 8
    5.330 ( 1.0649 )
    5.315 ( 1.2478 )
    5.235 ( 1.2578 )
        DAS28-ESR Week 16
    4.861 ( 1.1876 )
    5.059 ( 1.1682 )
    4.957 ( 1.1802 )
        DAS28-ESR Week 24
    5.216 ( 1.2510 )
    5.410 ( 1.2344 )
    5.432 ( 1.1891 )
        DAS28-ESR Week 36
    4.319 ( 1.2798 )
    4.689 ( 1.0077 )
    4.499 ( 1.1980 )
        DAS28-ESR Week 52 (EOS)
    4.435 ( 1.4375 )
    4.485 ( 1.4390 )
    4.391 ( 1.3947 )
    Statistical analysis title
    		 SAIT101:MabThera DAS28-ESR (Week 52)
    Statistical analysis description
    DAS28-ESR score SAIT101 vs MabThera at Week 52 ( EOS). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-ESR value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    MabThera v SAIT101
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9249
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.375
         upper limit
    		 0.413
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    		 SAIT101:Rituxan DAS28-ESR (Week 52)
    Statistical analysis description
    DAS28-ESR score SAIT101 vs Rituxan at Week 52 ( EOS). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-ESR value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8209
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.351
         upper limit
    		 0.421
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.201
    Statistical analysis title
    		 MabThera:Rituxan DAS28-ESR (Week 52)
    Statistical analysis description
    DAS28-ESR score MabThera vs Rituxan at Week 52 ( EOS). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-ESR value as a covariate. ANCOVA model contains treatment group only.
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8962
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.003
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.376
         upper limit
    		 0.301
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.205

    Secondary: Major Clinical Response (Continuous ACR70) for at Least 24 Weeks

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    End point title
    		 Major Clinical Response (Continuous ACR70) for at Least 24 Weeks
    End point description
    Efficacy endpoint: Major clinical response (continuous ACR70) from Baseline (Day 1) for at least 24 weeks
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 24
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    92
    86
    85
    Units: Score on a scale
    number (confidence interval 95%)
        Major Clinical Response Week 24
    1 (0.19 to 5.90)
    0 (0.00 to 4.28)
    0 (0.00 to 4.32)
        Major Clinical Repsonse Week 52 (EOS)
    2 (0.62 to 7.83)
    0 (0.00 to 4.53)
    1 (0.22 to 6.75)
    Statistical analysis title
    		 SAIT101:MabThera Major Clinical Response Week 52
    Statistical analysis description
    Week 24 Major Clinical Response SAIT101 vs MabThera. The 95% CIs for major clinical response rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    178
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Differnce (%)
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.56
         upper limit
    		 7.83
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.57
    Statistical analysis title
    		 SAIT101:Rituxan Major Clinical Response Week 52
    Statistical analysis description
    Week 52 (EOS) Major Clinical Response SAIT101 vs Rituxan. The 95% CIs for major clinical response rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    177
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Differnce (%)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.74
         upper limit
    		 6.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    2
    Statistical analysis title
    		 MabThera:rituxan Major Clinical Response Week 52
    Statistical analysis description
    Week 52 (EOS) Major Clinical Response MabThera vs Rituxan. The 95% CIs for major clinical response rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    171
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Differnce (%)
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.75
         upper limit
    		 3.39
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.24

    Secondary: Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52

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    End point title
    		 Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52
    End point description
    Efficacy endpoint: Proportion of participants with European League Against Rheumatism (EULAR) response (defined as good response, moderate response or no response) at weeks 8, 16, 24 36 and 52 (EOS). EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The DAS28-CRP was classified into 3 categories: low disease activity (<= 3.2), moderate disease activity (> 3.2 and <= 5.1) and high disease activity (> 5.1). Good response was defined as >1.2 improvement in the DAS28-CRP from baseline with low disease activity.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    92
    93
    Units: Score on a scale
    number (confidence interval 95%)
        Week 8 Good
    12 (7.54 to 21.21)
    14 (9.29 to 23.94)
    12 (7.54 to 21.21)
        Week 8 Good or Moderate
    30 (23.62 to 42.30)
    33 (26.82 to 46.05)
    33 (25.51 to 45.61)
        Week 16 Good
    20 (14.38 to 30.90)
    12 (7.62 to 21.43)
    13 (8.45 to 22.69)
        Week 16 Good or Moderate
    44 (37.47 to 57.36)
    42 (35.85 to 55.80)
    33 (26.82 to 46.05)
        Week 24 Good
    12 (7.71 to 21.65)
    7 (3.95 to 15.69)
    7 (4.05 to 16.04)
        Week 24 Good or Moderate
    30 (24.17 to 43.14)
    26 (21.28 to 40.19)
    23 (18.76 to 37.34)
        Week 36 Good
    27 (21.51 to 40.13)
    15 (11.41 to 28.01)
    27 (23.13 to 42.72)
        Week 36 Good or Moderate
    58 (54.15 to 73.56)
    50 (50.00 to 70.82)
    54 (53.62 to 73.70)
        Week 52 (EOS) Good
    34 (27.80 to 47.16)
    31 (26.37 to 46.11)
    32 (27.41 to 47.27)
        Week 52 (EOS) Good or Moderate
    59 (53.95 to 73.18)
    50 (46.98 to 67.33)
    63 (62.23 to 80.71)
    Statistical analysis title
    		 SAIT101:MabThera EULAR 'Good' Week 52
    Statistical analysis description
    Week 52 EULAR score 'Good' SAIT101 vs MabThera. EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The 95% CIs for EULAR response rate and treatment difference were derived using the Wilson Score method.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.59
         upper limit
    		 15.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.19
    Statistical analysis title
    		 SAIT101:Rituxan EULAR 'Good' Week 52
    Statistical analysis description
    Week 52 EULAR score 'Good' SAIT101 vs MabThera. EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The 95% CIs for EULAR response rate and treatment difference were derived using the Wilson Score method.
    Comparison groups
    SAIT101 v Rituxan
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    10.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.75
         upper limit
    		 14.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.21
    Statistical analysis title
    		 Mabthera:Rituxan EULAR 'Good' Week 52
    Statistical analysis description
    Week 52 EULAR score 'Good' SAIT101 vs MabThera. EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The 95% CIs for EULAR response rate and treatment difference were derived using the Wilson Score method.
    Comparison groups
    Rituxan v MabThera
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.14
         upper limit
    		 12.91
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.29

    Secondary: Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24

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    End point title
    		 Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24
    End point description
    Pharmacodynamic endpoint: proportion of participants (n) with depletion of CD19+ B-cell count up to week 24 (Pharmacodynamic analysis set).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 24 (Day 161)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    95
    96
    94
    Units: Subjects
    45
    46
    50
    No statistical analyses for this end point

    Secondary: Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion

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    End point title
    		 Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion
    End point description
    Pharmacodynamic endpoint: Time needed to CD19+ B-cell depletion in Part A (calculated as the first time CD19+ B-cell count below 20/µL minus time of first dosing in days rounded to 2 decimals)
    End point type
    Secondary
    End point timeframe
    Various
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    93
    93
    Units: Days
        least squares mean (standard deviation)
    1.524 ( 2.6274 )
    2.847 ( 9.1286 )
    2.223 ( 9.0833 )
    Attachments
    		 Untitled (Filename: Caplan-Meier time currve of B-Cell Depletion.PNG)
    No statistical analyses for this end point

    Secondary: Duration of CD19+ B-Cell Depletion

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    End point title
    		 Duration of CD19+ B-Cell Depletion
    End point description
    Pharmacodynamic endpoint: Duration of CD19+ B-Cell depletion. Only subjects that returned to non-depletion at or before Week 24 were included).
    End point type
    Secondary
    End point timeframe
    Various
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    36
    26
    21
    Units: Days
        least squares mean (standard deviation)
    78.444 ( 77.5290 )
    85.856 ( 73.4460 )
    77.290 ( 72.0557 )
    No statistical analyses for this end point

    Secondary: Percentage of CD19+ B-Cell Count Verses Baseline

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    End point title
    		 Percentage of CD19+ B-Cell Count Verses Baseline
    End point description
    Pharmacodynamic endpoint: percentage of CD19+ B-Cell count verses Baseline (Day 1). Recovery was defined as either CD19+ B-Cell count returned to Baseline or the lower limit of normal of 100 cell/µL at Week 24.
    End point type
    Secondary
    End point timeframe
    Various
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    93
    93
    90
    Units: Subjects
    5
    4
    3
    No statistical analyses for this end point

    Secondary: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24

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    End point title
    		 Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24
    End point description
    Pharmacodynamic endpoint. Area under the concentration time curve of CD19 B-cell count change at Day 15 (AUEC0-d15) and week 24 (AUEC0-w24) based on change from baseline and percent of baseline values.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Day 15 and week 24
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    72
    76
    73
    Units: Cells*day/µ
    least squares mean (confidence interval 95%)
        AUEC(0-d15)
    -2650.0 (-2786.0 to -2513.9)
    -2672.1 (-2804.9 to -2539.3)
    -2719.4 (-2855.3 to 2583.6)
        AUEC(0-d24)
    -32707.6 (-33128.1 to -32287.1)
    -33018.3 (-33440.4 to -32596.2)
    -33003.7 (-33442.8 to -32564.6)
    No statistical analyses for this end point

    Secondary: Change From Baseline in CD19+ B-cell Count During the Study Period

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    End point title
    		 Change From Baseline in CD19+ B-cell Count During the Study Period
    End point description
    Pharmacodynamic endpoint: Descriptive statistics (mean [SD]) of the change from baseline in CD19+ B-cell count during the study period (Day 15 [AUEC(0-d15] and Week 24 [AUEC(0-w24])
    End point type
    Secondary
    End point timeframe
    Baseline (Day1) to Day 15 and Week 24
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    72
    76
    73
    Units: Cells*day/µL
    least squares mean (standard deviation)
        AUEC(0-d15)
    -2729 ( 1915.3 )
    -2935 ( 2222.1 )
    -2367 ( 1978.1 )
        AUEC90-w24)
    -33500 ( 23881 )
    -36410 ( 22883 )
    -28500 ( 20878 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Immunoglobulin (Ig) G, IgM and IgA Levels

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    End point title
    		 Change From Baseline in Immunoglobulin (Ig) G, IgM and IgA Levels
    End point description
    Pharmacodynamic endpoint: Descriptive statistics (mean [SD]) of the change from baseline in CD19+ B-cell count during the study period (Day 15 [AUEC(0-d15] and Week 24 [AUEC(0-w24])
    End point type
    Secondary
    End point timeframe
    Screening to Week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    95
    96
    93
    Units: Mg/dL
    least squares mean (standard deviation)
        IgG Screening
    1231.0 ( 299.36 )
    1230.1 ( 365.54 )
    1203.4 ( 373.29 )
        IgG Week 8
    1108.0 ( 242.20 )
    1080.6 ( 279.75 )
    1038.5 ( 290.01 )
        IgG Week 16
    1105.2 ( 232.51 )
    1075.7 ( 277.51 )
    1038.5 ( 290.01 )
        IgG Week 24
    1114.6 ( 251.78 )
    1077.2 ( 265.55 )
    1023.2 ( 278.70 )
        IgG Week 52 (EOS)
    1102.0 ( 272.44 )
    1081.1 ( 285.13 )
    999.9 ( 232.03 )
        IgM Screening
    164.3 ( 76.06 )
    167.9 ( 100.16 )
    159.0 ( 81.36 )
        IgM Week 8
    137.5 ( 71.38 )
    132.6 ( 83.58 )
    128.9 ( 68.50 )
        IgM Week 16
    123.7 ( 61.08 )
    124.9 ( 85.71 )
    117.0 ( 60.44 )
        IgM Week 24
    123.3 ( 62.37 )
    117.1 ( 80.96 )
    109.9 ( 73.11 )
        IgM Week 36
    111.7 ( 56.89 )
    108.0 ( 77.79 )
    99.7 ( 56.38 )
        IgM Week 52 (EOS)
    109.6 ( 56.80 )
    107.6 ( 77.00 )
    95.2 ( 52.57 )
        IgA Screening
    321.11 ( 269.22 )
    283.4 ( 134.80 )
    342.9 ( 153.24 )
        IgA Week 8
    293.6 ( 176.04 )
    264.4 ( 121.41 )
    316.5 ( 146.15 )
        IgA Week 16
    301.8 ( 204.18 )
    253.0 ( 111.58 )
    312.7 ( 151.87 )
        IgA Week 24
    279.8 ( 119.87 )
    263.0 ( 121.15 )
    307.7 ( 147.92 )
        iGA Week 36
    283.8 ( 204.12 )
    259.2 ( 116.55 )
    297.1 ( 146.85 )
        IgA Week 52 (EOS)
    269.4 ( 116.74 )
    254.7 ( 115.38 )
    297.8 ( 138.63 )
        IgG week 36
    1076.6 ( 246.62 )
    1060.9 ( 305.12 )
    976.6 ( 249.11 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52

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    End point title
    		 Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52
    End point description
    Pharmacodynamic endpoint: Change from baseline (Day 1) in C-reactive protein (CRP) levels (mg/dL) at weeks 8, 16, 24, 36 and 52 (EOS)
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 52 (EOS)
    End point values
    		 SAIT101 MabThera Rituxan
    Number of subjects analysed
    95
    96
    93
    Units: Mg/dL
    least squares mean (standard deviation)
        CRP Day 1
    19.5 ( 29.5 )
    15.5 ( 20.76 )
    16.1 ( 17.64 )
        CRP Week 8
    12.5 ( 15.78 )
    12.3 ( 20.29 )
    10.4 ( 12.85 )
        CRP Week 16
    8.5 ( 11.78 )
    7.2 ( 9.02 )
    7.3 ( 6.90 )
        CRP Week 24
    9.5 ( 14.54 )
    8.3 ( 14.40 )
    7.9 ( 10.35 )
        CRP Week 36
    8.0 ( 10.33 )
    7.0 ( 10.38 )
    7.1 ( 9.72 )
        CRP Week 52 (EOS)
    9.8 ( 14.28 )
    9.1 ( 15.01 )
    7.3 ( 11.33 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events were collected from each subjects from the start of the first infusion of study drug on Day 1 until the Week 52 Data cut-off.
    Adverse event reporting additional description
    After the subject signed the Informed Consent form (ICF), but prior to the initiation of study drug, only serious adverse events (SAEs) caused by a protocol mandated procedure were reported (e.g. SAEs related to invasive procedures such as biopsies).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    SAIT101 Arm
    Reporting group description
    		 SAIT101 Arm (Safety Analysis Set)

    Reporting group title
    MabThera Arm
    Reporting group description
    		 Mabthera Arm (Safety Analysis Set)

    Reporting group title
    Rituxan Arm
    Reporting group description
    		 Rituxan Arm (Safety Analysis Set)

    Serious adverse events
    		 SAIT101 Arm MabThera Arm Rituxan Arm
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 98 (7.14%)
    7 / 98 (7.14%)
    13 / 98 (13.27%)
         number of deaths (all causes)
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    1
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 98 (1.02%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac Failure
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anemia
    Additional description: One subject in the MabThera group experienced the treatment-emergent SAE of anemia on study day 58 of treatment, which was reported as severe and considered as related to study treatment.
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 98 (1.02%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
    Additional description: One subject in the SAIT101 group experienced the treatment-emergent SAE of febrile neutropenia on study day 68 of treatment, which was reported as moderate in intensity and considered related to study treatment.
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 98 (0.00%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 98 (0.00%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 98 (0.00%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Interstitial lung disease
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 98 (1.02%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 98 (1.02%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 98 (1.02%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 98 (0.00%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis B reactivation
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 98 (0.00%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 98 (0.00%)
    2 / 98 (2.04%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 98 (1.02%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis bacterial
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 98 (0.00%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 98 (0.00%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 98 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural hematoma
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 98 (1.02%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 98 (0.00%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 SAIT101 Arm MabThera Arm Rituxan Arm
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    72 / 98 (73.47%)
    70 / 98 (71.43%)
    75 / 98 (76.53%)
    Injury, poisoning and procedural complications
    Urinary tract infection
         subjects affected / exposed
    13 / 98 (13.27%)
    4 / 98 (4.08%)
    8 / 98 (8.16%)
         occurrences all number
    14
    6
    10
    Infusion related reaction
         subjects affected / exposed
    2 / 98 (2.04%)
    2 / 98 (2.04%)
    7 / 98 (7.14%)
         occurrences all number
    2
    2
    8
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 98 (2.04%)
    5 / 98 (5.10%)
    2 / 98 (2.04%)
         occurrences all number
    2
    5
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 98 (3.06%)
    8 / 98 (8.16%)
    3 / 98 (3.06%)
         occurrences all number
    3
    9
    3
    Gastrointestinal disorders
    Gastritis
         subjects affected / exposed
    3 / 98 (3.06%)
    1 / 98 (1.02%)
    5 / 98 (5.10%)
         occurrences all number
    3
    1
    5
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    4 / 98 (4.08%)
    6 / 98 (6.12%)
    6 / 98 (6.12%)
         occurrences all number
    7
    6
    7
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 98 (7.14%)
    3 / 98 (3.06%)
    7 / 98 (7.14%)
         occurrences all number
    9
    4
    7
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 98 (5.10%)
    8 / 98 (8.16%)
    5 / 98 (5.10%)
         occurrences all number
    5
    10
    5

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Jun 2015
    Amendment 3 dated 02 June 2016 implemented the following changes: • correction of errors for text from previous versions • correction of grammatical errors • addition of missing words/text and deletion of certain text
    26 Oct 2015
    Amendment 1 dated 26 October 2015 implemented the following changes: • revised the criteria of study population • clarified study design • terminology for premedication was updated • clarified the definition for clinical remission • clarified inclusion and exclusion criteria • revised text for subject withdrawal and updated the discontinuation criteria • addition of text related to interim analysis • modified schedule of assessments • pharmacodynamic variables were clarified • updated the washout period for prior medications • administrative changes were made, correction of errors for text from previous versions and addition/deletion of certain text to clarify the important points
    19 May 2016
    Amendment 2 dated 19 May 2016 implemented the following changes: • criteria of study population and phase of study development were revised • modified the study design of MabThera group in Part B • updated the terminology for premedication • addition of text related to week 4 interim analysis, and criteria for unblinding at week 24 was clarified • modified the inclusion criteria for the dose of MTX given as a current treatment forRA • main criteria of evaluation were clarified by specifying the study endpoints • withdrawn subjects were included in the PK analysis if the eligibility criteria for PKdata set were met • modified the text related to primary safety concerns associated with rituximab • updated the text related to study treatment formulationArchigen Biotech Limited • updated the absolute neutrophil count and platelet count prior to second course of study treatment • clarified the management of hepatitis reactivation and other infections during rituximab therapy • revisions were made in inclusion and exclusion criteria text for clarity • subjects who lacked efficacy could be included in the PK and efficacy analysis.subjects receiving rescue therapy prior to week 24 were considered not to be eligible for second course of infusion • modified schedule of assessments • criteria for SAE, ADR, and AESI, and reporting of AE and SAE were clarified • added text for PML and mucocutaneous reactions • updated criteria for diagnosing anaphylaxis • added text for changes in clinical laboratory assessment results • updated the text for sample size and analysis sets, handling missing values and outliers • clarified the text for study treatment preparation and disposal of unused study treatments • revisions in text made to clarify the important points • correction of grammatical, typo and certain editorial and consistency errors
    27 Apr 2017
    Amendment 4 dated 27 April 2017 implemented the following changes: • name of finished product terminology updated as proposed biosimilar to rituximab • Sixty days of screening time needed for prophylaxis of latent TB were allowed • assessments to be done within 30 days of screening period was clarified • unnecessary restriction in time duration for premedication intake was deleted • eligibility criteria on latent TB was clarified • sampling time point was clarified • time point of second interim safety analysis was changed to align with DSMB review timepoint • inclusion criteria related to contraception and pregnancy testing was changed as per clinical trial facilitation group guidance • immunogenicity sampling at immune-response-related was added for intensive monitoring • serious AE collection changed to collect minimally required information by ICH E6 R2 (2015. 6. 11) • clarified that any AE were followed up to resolution • revisions in text made to clarify the important points • correction of certain editorial and consistency errors

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

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