Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the Efficacy, Safety, and Immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in Patients with Low Tumor Burden Follicular Lymphoma

    Summary
    EudraCT number
    		 2016-001966-27
    Trial protocol
    		 HU   ES   GB   CZ   BG   FR   LV   HR  
    Global end of trial date
    10 Jan 2020

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    AGB002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02809053
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Archigen Biotech Ltd
    Sponsor organisation address
    1 Francis Crick Avenue, Cambridge, United Kingdom, CB2 0QH
    Public contact
    Medical Director , Archigen Biotech Ltd, +44 20 3749 5000, info@archigenbio.com
    Scientific contact
    Medical Director , Archigen Biotech Ltd, +44 20 3749 5000, 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
    Interim
    Date of interim/final analysis
    09 Oct 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    17 Jul 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Jan 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy of SAIT101 with rituximab (MabThera®) when administered as a first-line immunotherapy in patients with low tumor burden follicular lymphoma (LTBFL).
    Protection of trial subjects
    This study was performed in compliance with International Council for Harmonisation Good Clinical Practices (GCP), including the archiving of essential documents as well as the ethical principles of the Declaration of Helsinki. The study protocol, all study protocol amendments, written study subject information, informed consent form (ICF), Investigator’s Brochure and any other relevant documents were reviewed and approved by an independent ethics committee (IEC) or institutional review board (IRB) at each study center.
    Background therapy
    		 No additional background cancer therapies were allowed in the study including other experimental drug, or a concomitant chemotherapy, anticancer hormonal therapy, radiotherapy, or immunotherapy. The use of concomitant therapy, including prescription and non-prescription drugs, non-drug therapy, dietary supplements, and herbal prescriptions, were permitted as appropriate to treat AEs or comorbid conditions.
    Evidence for comparator
    		 This study was designed to compare the efficacy, pharmacokinetic (PK), pharmacodynamics (PD), safety, and immunogenicity of SAIT101 with rituximab (MabThera®). SAIT101 is being developed as a proposed biosimilar to rituximab.
    Actual start date of recruitment
    18 Jan 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 56 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 40
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    Croatia: 2
    Country: Number of subjects enrolled
    Czech Republic: 50
    Country: Number of subjects enrolled
    France: 15
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Hungary: 13
    Country: Number of subjects enrolled
    United States: 5
    Country: Number of subjects enrolled
    Korea, Republic of: 22
    Country: Number of subjects enrolled
    Turkey: 18
    Country: Number of subjects enrolled
    Italy: 21
    Country: Number of subjects enrolled
    Mexico: 2
    Country: Number of subjects enrolled
    South Africa: 8
    Country: Number of subjects enrolled
    Australia: 8
    Country: Number of subjects enrolled
    Chile: 3
    Country: Number of subjects enrolled
    Ukraine: 13
    Country: Number of subjects enrolled
    Thailand: 4
    Country: Number of subjects enrolled
    Serbia: 4
    Country: Number of subjects enrolled
    Panama: 1
    Country: Number of subjects enrolled
    India: 32
    Country: Number of subjects enrolled
    Georgia: 4
    Country: Number of subjects enrolled
    Guatemala: 5
    Country: Number of subjects enrolled
    Belarus: 15
    Country: Number of subjects enrolled
    Egypt: 15
    Country: Number of subjects enrolled
    Philippines: 2
    Worldwide total number of subjects
    315
    EEA total number of subjects
    154
    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)
    172
    From 65 to 84 years
    143
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 One hundred and one study centres in 29 countries participated in the study. The first participant was enrolled into the study on the 18 January 2017 and the last participant completed week 28 (primary analysis cut-off) on the 17 July 2019.

    Pre-assignment
    Screening details
    		 -

    Pre-assignment period milestones
    Number of subjects started
    		 315
    Number of subjects completed
    		 315

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SAIT101
    Arm description
    		 SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3 and 4.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    SAIT101
    Investigational medicinal product code
    SAIT101
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3 and 4.

    Arm title
    		 MabThera
    Arm description
    		 MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    MabThera
    Investigational medicinal product code
    Other name
    Rituximab
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4.

    Number of subjects in period 1
    		SAIT101 MabThera
    Started
    157
    158
    Completed
    150
    152
    Not completed
    7
    6
         Consent withdrawn by subject
    2
    3
         Disease progression
    2
    1
         Lost to follow-up
    3
    1
         Death
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    SAIT101
    Reporting group description
    		 SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3 and 4.

    Reporting group title
    MabThera
    Reporting group description
    		 MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4.

    Reporting group values
    		 SAIT101 MabThera Total
    Number of subjects
    		 157 158 315
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.8 ( 12.38 ) 58.4 ( 12.78 ) -
    Gender categorical
    Units: Subjects
        Female
    		 86 88 174
        Male
    		 71 70 141
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 11 7 18
        Not Hispanic or Latino
    		 136 139 275
        Unknown or Not Reported
    		 10 12 22
    Females of childbearing potential
    Men and women of childbearing potential used highly effective methods of contraception during the course of the treatment period and for at least 12 months after the last infusion of study treatment. A man or woman was of childbearing potential if, in the opinion of the Investigator, he or she was biologically capable of having children and was sexually active.
    Units: Subjects
        Yes
    		 24 20 44
        No
    		 133 138 271
    Eastern Co-operative Oncology Group (ECOG) performance status
    Measure Description: The ECOG score is used in the evaluation of cancer patients and can help with prognosis and management of the malignant condition because performance status is highly correlated with survival. A higher ECOG rating score generally equates to a worst outcome. ECOG scores 0 and 1 are defined as: - ECOG Score 0: Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction); - ECOG Score 1: Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
    Units: Subjects
        ECOG Score 0
    		 132 118 250
        ECOG Score 1
    		 25 40 65
    Antidrug Antibody (ADA) Status at Baseline
    Units: Subjects
        Postive
    		 3 2 5
        Negative
    		 138 148 286
        Not available
    		 16 8 24
    Ann Arbor Staging
    Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma and non-Hodgkin lymphoma. Stage I indicates that the cancer is located in a single region. Stage II indicates that the cancer is located in two separate regions, an affected lymph node or lymphatic organ and a second affected area. Stage III indicates that the cancer has spread to both sides of the diaphragm. Stage IV indicates diffuse or disseminated involvement of one or more extralymphatic organs.
    Units: Subjects
        Stage I
    		 1 0 1
        Stage II
    		 39 37 76
        Stage III
    		 72 69 141
        Stage IV
    		 45 52 97
    Type of Ann Arbor Staging
    Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma (formerly designated Hodgkin's disease) and non-Hodgkin lymphoma (abbreviated NHL). It was initially developed for Hodgkin's, but has some use in NHL. It has roughly the same function as TNM staging in solid tumors Ann Arbor Clinical Stage (CS) as obtained by doctor's examination and tests, An Arbor Pathological Stage (PS) as obtained by exploratory laparotomy with splenectomy.
    Units: Subjects
        Clinical Stage
    		 144 140 284
        Pathological Stage
    		 13 18 31
    Risk Groups According to Follicular Lymphoma International Prognostic Index (FLIP-2) Score
    Follicular Lymphoma International Prognostic Index (FLIPI) score of 0 to 1 is considered "low risk" with a 10 year overall survival of 70%. A score of 2 is considered "intermediate risk" with a 10 year overall survival of 50%. Finally, a score of ≥ 3 is considered "high risk" with a 10 year overall survival of 35%
    Units: Subjects
        Low Risk (0 to 1 risk factors)
    		 102 103 205
        Intermediate Risk (2 risk factors)
    		 40 41 81
        High Risk (Greater than or equal to 3 risk factor
    		 15 14 29
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 1 2
        Asian
    		 31 30 61
        Black or African American
    		 1 1 2
        Native Hawaiian or other Pacific Islander
    		 0 0 0
        White
    		 115 111 226
        Unknown
    		 2 4 6
        Not reported
    		 7 11 18
    Height
    Units: Cm
        arithmetic mean (standard deviation)
    		 165.96 ( 9.436 ) 165.71 ( 10.650 ) -
    Weight
    Weight at baseline
    Units: Kg
        arithmetic mean (standard deviation)
    		 73.80 ( 15.107 ) 73.54 ( 16.602 ) -
    Body Mass Index
    Units: Kg/m^2
        arithmetic mean (standard deviation)
    		 26.76 ( 4.857 ) 26.22 ( 4.967 ) -
    Body Surface Area
    Units: m^2
        arithmetic mean (standard deviation)
    		 1.812 ( 0.2032 ) 1.807 ( 0.2332 ) -
    Disease duration
    Disease duration was derived from initial disease diagnosis date to the date of informed consent. Note that initial disease diagnosis can be confirmed by biopsy after informed consent.
    Units: Years
        arithmetic mean (standard deviation)
    		 0.937 ( 2.1528 ) 0.934 ( 2.5793 ) -
    Subject analysis sets

    Subject analysis set title
    Full Anaysis Set (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS consisted of all RAN subjects in accordance with the intended treatment group, regardless of the treatment actually received. However, subjects who did not qualify for randomization and were inadvertently randomized into the study were excluded from the FAS, provided these subjects did not receive study treatment. The FAS was considered as the primary analysis set for the primary efficacy endpoint and 1 of the analysis sets for other efficacy endpoints. The FAS for exploratory analysis (FASEXP) consisted of all FAS subjects who had their tumors assessment measured by PET CT scan.

    Subject analysis set title
    Pharmacokinetic Analysis Set (PKS)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic Analysis Set (PKS) included all subjects who received at least 1 dose of study treatment, had at least 1 measured drug serum concentration at a scheduled time point postdose, and had no major protocol deviations or violations thought to significantly affect the PK of the drug. Subjects in the PKS were analyzed according to the treatment received.

    Subject analysis set title
    Pharmacodynamic Analysis Set (PDS)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacodynamic Analysis Set (PDS) included all subjects who received at least 1 dose of study treatment, had at least 1 measured PD variable (CD19+ B-cell count) at a scheduled time point postdose, and had no major protocol deviations or violations thought to significantly affect the PD of the drug. Subjects in the PDS were analyzed according to the treatment received.

    Subject analysis set title
    Safety Anaysis Set (SAF)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The Safety Analysis Set (SAF) consisted of all randomised subjects who received at least 1 dose of study treatment. Subjects were analyzed according to the treatment received. The SAF was to be used as the basis for all safety analyses up to week 52. If there was any doubt whether a subject was treated or not, they were assumed treated for the purposes of analysis.

    Subject analysis sets values
    		 Full Anaysis Set (FAS) Pharmacokinetic Analysis Set (PKS) Pharmacodynamic Analysis Set (PDS) Safety Anaysis Set (SAF)
    Number of subjects
    315
    148
    148
    315
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    58.1 ( 12.57 )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    174
        Male
    141
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    18
        Not Hispanic or Latino
    275
        Unknown or Not Reported
    22
    Females of childbearing potential
    Men and women of childbearing potential used highly effective methods of contraception during the course of the treatment period and for at least 12 months after the last infusion of study treatment. A man or woman was of childbearing potential if, in the opinion of the Investigator, he or she was biologically capable of having children and was sexually active.
    Units: Subjects
        Yes
    44
        No
    Eastern Co-operative Oncology Group (ECOG) performance status
    Measure Description: The ECOG score is used in the evaluation of cancer patients and can help with prognosis and management of the malignant condition because performance status is highly correlated with survival. A higher ECOG rating score generally equates to a worst outcome. ECOG scores 0 and 1 are defined as: - ECOG Score 0: Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction); - ECOG Score 1: Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
    Units: Subjects
        ECOG Score 0
    250
        ECOG Score 1
    65
    Antidrug Antibody (ADA) Status at Baseline
    Units: Subjects
        Postive
    5
        Negative
    286
        Not available
    24
    Ann Arbor Staging
    Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma and non-Hodgkin lymphoma. Stage I indicates that the cancer is located in a single region. Stage II indicates that the cancer is located in two separate regions, an affected lymph node or lymphatic organ and a second affected area. Stage III indicates that the cancer has spread to both sides of the diaphragm. Stage IV indicates diffuse or disseminated involvement of one or more extralymphatic organs.
    Units: Subjects
        Stage I
    1
        Stage II
    76
        Stage III
    141
        Stage IV
    30
    Type of Ann Arbor Staging
    Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma (formerly designated Hodgkin's disease) and non-Hodgkin lymphoma (abbreviated NHL). It was initially developed for Hodgkin's, but has some use in NHL. It has roughly the same function as TNM staging in solid tumors Ann Arbor Clinical Stage (CS) as obtained by doctor's examination and tests, An Arbor Pathological Stage (PS) as obtained by exploratory laparotomy with splenectomy.
    Units: Subjects
        Clinical Stage
    284
        Pathological Stage
    31
    Risk Groups According to Follicular Lymphoma International Prognostic Index (FLIP-2) Score
    Follicular Lymphoma International Prognostic Index (FLIPI) score of 0 to 1 is considered "low risk" with a 10 year overall survival of 70%. A score of 2 is considered "intermediate risk" with a 10 year overall survival of 50%. Finally, a score of ≥ 3 is considered "high risk" with a 10 year overall survival of 35%
    Units: Subjects
        Low Risk (0 to 1 risk factors)
    205
        Intermediate Risk (2 risk factors)
    81
        High Risk (Greater than or equal to 3 risk factor
    29
    Race
    Units: Subjects
        American Indian or Alaska Native
        Asian
        Black or African American
        Native Hawaiian or other Pacific Islander
        White
        Unknown
        Not reported
    Height
    Units: Cm
        arithmetic mean (standard deviation)
    165.84 ( 10.048 )
    ( )
    ( )
    ( )
    Weight
    Weight at baseline
    Units: Kg
        arithmetic mean (standard deviation)
    73.67 ( 15.850 )
    ( )
    ( )
    ( )
    Body Mass Index
    Units: Kg/m^2
        arithmetic mean (standard deviation)
    26.71 ( 4.905 )
    ( )
    ( )
    ( )
    Body Surface Area
    Units: m^2
        arithmetic mean (standard deviation)
    1.810 ( 0.2184 )
    ( )
    ( )
    ( )
    Disease duration
    Disease duration was derived from initial disease diagnosis date to the date of informed consent. Note that initial disease diagnosis can be confirmed by biopsy after informed consent.
    Units: Years
        arithmetic mean (standard deviation)
    0.935 ( 2.3626 )
    ( )
    ( )
    ( )

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    SAIT101
    Reporting group description
    		 SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3 and 4.

    Reporting group title
    MabThera
    Reporting group description
    		 MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4.

    Subject analysis set title
    Full Anaysis Set (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS consisted of all RAN subjects in accordance with the intended treatment group, regardless of the treatment actually received. However, subjects who did not qualify for randomization and were inadvertently randomized into the study were excluded from the FAS, provided these subjects did not receive study treatment. The FAS was considered as the primary analysis set for the primary efficacy endpoint and 1 of the analysis sets for other efficacy endpoints. The FAS for exploratory analysis (FASEXP) consisted of all FAS subjects who had their tumors assessment measured by PET CT scan.

    Subject analysis set title
    Pharmacokinetic Analysis Set (PKS)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic Analysis Set (PKS) included all subjects who received at least 1 dose of study treatment, had at least 1 measured drug serum concentration at a scheduled time point postdose, and had no major protocol deviations or violations thought to significantly affect the PK of the drug. Subjects in the PKS were analyzed according to the treatment received.

    Subject analysis set title
    Pharmacodynamic Analysis Set (PDS)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacodynamic Analysis Set (PDS) included all subjects who received at least 1 dose of study treatment, had at least 1 measured PD variable (CD19+ B-cell count) at a scheduled time point postdose, and had no major protocol deviations or violations thought to significantly affect the PD of the drug. Subjects in the PDS were analyzed according to the treatment received.

    Subject analysis set title
    Safety Anaysis Set (SAF)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The Safety Analysis Set (SAF) consisted of all randomised subjects who received at least 1 dose of study treatment. Subjects were analyzed according to the treatment received. The SAF was to be used as the basis for all safety analyses up to week 52. If there was any doubt whether a subject was treated or not, they were assumed treated for the purposes of analysis.

    Primary: Overall Response Rate (ORR) at Week 28

    		 Close Top of page
    End point title
    		 Overall Response Rate (ORR) at Week 28
    End point description
    Overall Response Rate (ORR) (Complete Response [CR] + Partial Response [PR]) at Week 28, as defined by International Working Group (IWG) criteria 2007. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. The 95% CI for overall response rate (ORR) was calculated using the Exact method and combined using the Rubin's rule when multiple imputation was applicable.
    End point type
    Primary
    End point timeframe
    Baseline (Day 0) to Week 28
    End point values
    		 SAIT101 MabThera Full Anaysis Set (FAS)
    Number of subjects analysed
    157
    158
    157
    Units: Percentage of subjects
    number (confidence interval 95%)
        Overall Response Rate
    66.3 (58.64 to 73.87)
    70.6 (63.21 to 77.97)
    66.3 (58.64 to 73.87)
    Attachments
    		 Plot for Overall Tumor Assessment
    Statistical analysis title
    		 Adjusted Difference Rate (%) in ORR
    Statistical analysis description
    The 95%CI (confidence interval) for the difference in the overall response rate (ORR) was calculated using the Newcombe-Wilson method based on CMH (Cochran-Mantel-Haenszel) weight with stratification factor FLIPI-2 (low, intermediate and high risk).
    Comparison groups
    MabThera v SAIT101
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Adjusted Difference Rate (%)
    Point estimate
    -4.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.8
         upper limit
    		 6.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.4

    Primary: Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4)

    		 Close Top of page
    End point title
    		 Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4)
    End point description
    Pharmacokinetic endpoint: truncated area under the concentration-time curve (AUC) over the first (Day 1) and fourth (Day 22) dosing intervals (AUC0 168,w1, AUC0-168,w4).
    End point type
    Primary
    End point timeframe
    Baseline (Day 0) to dosing on Week 1 and Week 4
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    76
    72
    Units: H*µg/ml
    geometric mean (geometric coefficient of variation)
        AUC0-168, week 1
    20140 ( 18.7 )
    19860 ( 18.3 )
        AUC0-168, week 4
    41290 ( 19 )
    42600 ( 19.4 )
    Statistical analysis title
    		 Geometric least square (GLS) Mean Ratio
    Statistical analysis description
    Statistical Comparison: geometric least square (GLS) Mean Ratio (90% Confidence Interval (CI)) (%) of SAIT101 versus MabThera Area Under the Concentration time Curve Day 0 to Week 1 (AUC0-168,w1) (h×µg/mL). The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment
    Comparison groups
    MabThera v SAIT101
    Number of subjects included in analysis
    148
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [1]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    101.39
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 95.86
         upper limit
    		 107.24
    Notes
    [1] - Standard acceptance limits for bioequivalence (80.00% to 125.00%). Comparison: SAIT101 versus MabThera. Equivalence was demonstrated for SAIT101 and MabThera with exposure pharmacokinetic parameter AUC0-168,w1 within the standard acceptance limits for bioequivalence (80.00% to 125.00%).

    Secondary: Overall Response Rate (ORR) at Week 12

    		 Close Top of page
    End point title
    		 Overall Response Rate (ORR) at Week 12
    End point description
    Overall Response Rate (ORR) = Complete Response (CR) + Partial Response (PR). Tumour assessments were assessed by central imaging review per the International Working Group (IWG) Criteria 2007. The 95% CI for overall response rate (ORR) was calculated using the Exact method and combined using the Rubin's rule when multiple imputation was applicable.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 12
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    157
    158
    Units: Percentage of subjects
    number (confidence interval 95%)
        ORR at Week 12
    59.6 (51.16 to 67.62)
    70.0 (61.99 to 77.20)
    Attachments
    		 Plot for Overall Tumor Assessment and ORR
    Statistical analysis title
    		 Adjusted Difference Rate of ORR at Week 12
    Statistical analysis description
    The 95%CI (confidence interval) for the difference in the overall response rate (ORR) was calculated using the Newcombe-Wilson method based on CMH (Cochran-Mantel-Haenszel) weight with stratification factor FLIPI-2 (low, intermediate and high risk).
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Adjusted Difference Rate
    Point estimate
    -10.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.92
         upper limit
    		 0.61
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.42
    Notes
    [2] - Comparison: SAIT101 versus MabThera

    Secondary: Complete Response (CR) at Weeks 12 and 2

    		 Close Top of page
    End point title
    		 Complete Response (CR) at Weeks 12 and 2
    End point description
    Efficacy Endpoint: Complete Response (CR) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 12 and Week 28
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    145
    148
    Units: Number of subjects
        CR at Week 12
    39
    37
        CR at Week 28
    51
    50
    No statistical analyses for this end point

    Secondary: Partial Response (PR) at Weeks 12 and 28

    		 Close Top of page
    End point title
    		 Partial Response (PR) at Weeks 12 and 28
    End point description
    Efficacy Endpoint: Partial Response (PR) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 12 and Week 28.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    145
    148
    Units: Number of subjects
        PR at Week 12
    48
    68
        PR at Week 28
    47
    53
    No statistical analyses for this end point

    Secondary: Stable Disease (SD) at Weeks 12 and 28

    		 Close Top of page
    End point title
    		 Stable Disease (SD) at Weeks 12 and 28
    End point description
    Efficacy endpoint: number of participants with Stable Disease (SD) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 12 and Week 28
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    145
    148
    Units: Number of subjects
        SD at Week 12
    50
    39
        SD at Week 28
    22
    27
    No statistical analyses for this end point

    Secondary: Progressive Disease (PD) at 12 and 28 Weeks

    		 Close Top of page
    End point title
    		 Progressive Disease (PD) at 12 and 28 Weeks
    End point description
    Efficacy endpoint: number of participants with Progressive Disease (PD) at 12 and 28 Weeks. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0)to Week 12 and Week 28.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    145
    148
    Units: Number of subjects
        PD at Week 12
    4
    1
        PD at Week 28
    20
    11
    No statistical analyses for this end point

    Secondary: Time to Event (TTE)

    		 Close Top of page
    End point title
    		 Time to Event (TTE)
    End point description
    Efficacy Endpoint. Time to Event (TTE) is defined as the time of randomisation to the date when an event occurred for a maximum follow-up period of 32 weeks from baseline; an event is disease progression, death due to any cause, or the start of new treatment for follicular lymphoma, whichever comes first.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to time of event or up to a maximum of 32 weeks, whichever is sooner
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    157
    158
    Units: Months
    arithmetic mean (standard deviation)
        Time to event
    23.50 ( 7.500 )
    24.08 ( 6.767 )
    Attachments
    		 Kaplan Meier Plot for Time to Event Full Analysis
    Statistical analysis title
    		 Time to Event (TTE) Hazard Ratio (HR)
    Statistical analysis description
    Time to Event (TTE) Hazard Ratio (HR) of SAIT101:MabThera. The TTE is defined as the time from the date of randomization to the date when an event occurs; an event is disease progression as assessed by Investigator, death due to any cause, or the start of new treatment, whichever comes first.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.724
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.853
         upper limit
    		 3.482
    Notes
    [3] - The estimated Hazard Ratio with 95% CI was obtained from Cox regression model; however, stratification factors, ie, FLIPI-2 (low, intermediate and high risk), were only taken into account if FLIPI-2 score=all.

    Secondary: Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4)

    		 Close Top of page
    End point title
    		 Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4)
    End point description
    Pharmacokinetic endpoint: maximum plasma concentration (Cmax, �g/ml ) after the first dose (Week 1) and the fourth dose (week 4) (Cmax,w1, Cmax,w4).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to dosing on Week 1 and Week 4
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    76
    72
    Units: µg/m
    geometric mean (geometric coefficient of variation)
        Cmax Week 1
    199.3 ( 22.1 )
    200.6 ( 27.5 )
        Cmax Week 4
    333.6 ( 22.8 )
    336.2 ( 20.2 )
    Statistical analysis title
    		 Cmax GLS Mean Ratio at Week 1
    Statistical analysis description
    Statistical Comparison: geometric least square (GLS) Mean Ratio (90% CI) (%) of SAIT101 versus MabThera maximum plasma concentration at Week 1 (Cmax,w1) (h×µg/mL). The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment.
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    148
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [4]
    Method
    Parameter type
    		 GLS Mean Difference
    Point estimate
    99.35
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 90.85
         upper limit
    		 104.4
    Notes
    [4] - Standard acceptance limits for bioequivalence (80.00% to 125.00%). Comparison: SAIT101 versus MabThera. Pharmacokinetic equivalence was demonstrated for SAIT101 and MabThera with Cmax,w1 exposure within the standard acceptance limits for bioequivalence (80.00% to 125.00%).
    Statistical analysis title
    		 Cmax GLS Mean Ratio at Week 4
    Statistical analysis description
    Statistical Comparison: geometric least square (GLS) Mean Ratio (90% CI) (%) of SAIT101 versus MabThera maximum plasma concentration at Week 4 (Cmax,w1) (h׵g/mL). The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    148
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [5]
    Method
    Parameter type
    		 GLS Mean Difference
    Point estimate
    99.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 92.96
         upper limit
    		 105.92
    Notes
    [5] - Standard acceptance limits for bioequivalence (80.00% to 125.00%). Comparison: SAIT101 versus MabThera. Pharmacokinetic equivalence was demonstrated for SAIT101 and MabThera with exposure PK parameter Cmax,w4 within the standard acceptance limits for bioequivalence (80.00% to 125.00%).

    Secondary: Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC).

    		 Close Top of page
    End point title
    		 Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC).
    End point description
    Pharmacokinetic endpoint: accumulation ratio for the Area Under the Concentration Time Cure 0 to 168 hours (AUC0-168) obtained from the fourth dose (Week 4) versus the first dose (Week 1) (RAUC). Accumulation ratio, calculated for AUC0-168 as (AUC0 168,w4/AUC0 168,w1).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to dosing on Week 1 and Week 4
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    76
    72
    Units: µg/m
    geometric mean (geometric coefficient of variation)
        RAUC
    2.075 ( 17.2 )
    2.137 ( 21.0 )
    No statistical analyses for this end point

    Secondary: Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax)

    		 Close Top of page
    End point title
    		 Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax)
    End point description
    Pharmacokinetic endpoint: accumulation ratio for maximum plasma (Cmax) ratio from the fourth dose on Week 4 versus the first dose of treatment on Week 1 (RCmax). Accumulation ratio, calculated for Cmax as (Cmax,w4/Cmax,w1).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to dosing on Week 1 and Week 4.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    76
    72
    Units: µg/ml
    geometric mean (geometric coefficient of variation)
        RCmax
    1.706 ( 23.2 )
    1.671 ( 31.0 )
    No statistical analyses for this end point

    Secondary: Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough).

    		 Close Top of page
    End point title
    		 Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough).
    End point description
    Pharmacokinetic endpoint: trough plasma concentration (Ctrough) during the dosing phase on Days 1, 8, 15, 22, and 29. Concentrations at predose on Days 8, 15, and 22 (�g/mL) and the time equivalent to the predose on Day 29, obtained directly from the observed concentration versus time data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Days 1, 8, 15, 22 and 29.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    76
    72
    Units: µg/mL
    geometric mean (geometric coefficient of variation)
        Ctrough Day 8
    60.60 ( 45.5 )
    61.00 ( 43.4 )
        Ctrough Day 15
    108.1 ( 26.0 )
    107.3 ( 32.0 )
        Ctrough Day 22
    143.0 ( 23.8 )
    143.3 ( 30.0 )
        Ctrough Day 29
    181.7 ( 22.1 )
    190.4 ( 26.1 )
    Statistical analysis title
    		 Ctrough GLS mean ratio
    Statistical analysis description
    Statistical Comparison: geometric least square (GLS) Mean Ratio (90% CI) (%) of SAIT101 versus MabThera trough plasma concentration at the end of the dosing period (Day 29) (Ctrough,d29) (µg/mL) . The statistical comparison of the log-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment
    Comparison groups
    SAIT101 v MabThera
    Number of subjects included in analysis
    148
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [6]
    Method
    Parameter type
    		 GLS mean ratio
    Point estimate
    95.45
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 88.85
         upper limit
    		 102.55
    Notes
    [6] - Standard acceptance limits for bioequivalence (80.00% to 125.00%). Comparison: SAIT101 versus MabThera. Pharmacokinetic equivalence was demonstrated for SAIT101 and MabThera with exposure PK parameter Ctrough,d29 within the standard acceptance limits for bioequivalence (80.00% to 125.00%).

    Secondary: Observed Change From Baseline and Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28

    		 Close Top of page
    End point title
    		 Observed Change From Baseline and Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28
    End point description
    Pharmacodynamic Endpoint: Arithmetic mean observed change from baseline and percent change from baseline of B-lymphocyte antigen cluster of differentiation 19 (CD-19+ B-cell) counts (cells/&#956;L) up to Week 28 by treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    76
    72
    Units: cells/&#956;L
    arithmetic mean (standard deviation)
        Week 1 Mean Change from Baseline
    -128.0 ( 115.71 )
    -141.6 ( 120.90 )
        Week 1 % Change from Baseline
    -89.02 ( 26.324 )
    -95.58 ( 8.294 )
        Week 2 Mean Change from Baseline
    -144.1 ( 123.34 )
    -146.8 ( 138.76 )
        Week 2 % Change from Baseline
    -100.00 ( 0.000 )
    -100.00 ( 0.000 )
        Week 3 Mean Change from Baseline
    -142.8 ( 122.63 )
    -157.4 ( 102.03 )
        Week 3 % Change from Baseline
    -100.00 ( 0.000 )
    -100.00 ( 0.000 )
        Week 4 Mean Change from Baseline
    -141.5 ( 122.92 )
    -141.2 ( 102.03 )
        Week 4 % Change from Baseline
    -100.00 ( 0.000 )
    -100.00 ( 0.000 )
        Week 5 Mean Change from Baseline
    -140.0 ( 120.74 )
    -158.5 ( 134.27 )
        Week 5 % Change from Baseline
    -100.00 ( 0.000 )
    -100.00 ( 0.000 )
        Week 12 Mean Change from Baseline
    -144.2 ( 122.09 )
    -160.1 ( 134.09 )
        Week 12 % Change from Baseline
    -100.00 ( 0.000 )
    -100.00 ( 0.000 )
        Week 20 Mean Change from Baseline
    -140.8 ( 117.98 )
    -159.5 ( 135.63 )
        Week 20 % Change from Baseline
    -100.00 ( 0.000 )
    -100.00 ( 0.000 )
        Week 28 Mean Change from Baseline
    -136.6 ( 122.80 )
    -142.2 ( 134.79 )
        Week 28 % Change from Baseline
    -97.42 ( 12.749 )
    -96.78 ( 13.476 )
    No statistical analyses for this end point

    Secondary: Area Under the Curve Change From Baseline B-lymphocyte CD19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval

    		 Close Top of page
    End point title
    		 Area Under the Curve Change From Baseline B-lymphocyte CD19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval
    End point description
    Pharmacodynamic Endpoint: Area under the change from baseline CD19+ B-cell count time curve (AUEC) over the first dosing interval on week 1 from time 0 to the time prior to the second dose (AUEC0 168,w1), AUEC over the second dosing interval on week 2 from time 0 to the time prior to the third dose (AUEC0-168,w2), AUEC over the third dosing interval on week 3 from time 0 to the time prior to the fourth dose (AUEC0-168,w3), AUEC over the fourth dosing interval on week 4 from time 0 to 168 hours post dose (AUEC0-168,w4), AUEC from time 0 on week 1 to the time point on week 12 (AUEC0-w12), AUEC from time 0 on week 1 to the time point on week 28 (AUEC0 w28) for the change from baseline CD19+ B-cell count data
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    76
    72
    Units: cellsxday/µL
    arithmetic mean (standard deviation)
        AUEC0-168,w1 (cellsxday/µL)
    -946.0 ( 830.29 )
    -1000 ( 891.82 )
        AUEC0-168,w2 (cellsxday/µL)
    -987.2 ( 997.57 )
    -1104 ( 947.68 )
        AUEC0-168,w3 (cellsxday/µL)
    -944.8 ( 910.79 )
    -1073 ( 930.95 )
        AUEC0-168,w4 (cellsxday/µL)
    -956.3 ( 728.52 )
    -1196 ( 1153.7 )
        AUEC0-w12 (cellsxday/µL)
    -11330 ( 9854.1 )
    -12280 ( 10185 )
        AUEC0-w28 (cellsxday/µL)
    -26370 ( 22794 )
    -28860 ( 25439 )
    No statistical analyses for this end point

    Secondary: Normalized Area Under the Curve Change From Baseline B-lymphocyte CD19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval

    		 Close Top of page
    End point title
    		 Normalized Area Under the Curve Change From Baseline B-lymphocyte CD19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval
    End point description
    Pharmacodynamic Endpoint: Area under the change from baseline CD19+ B-cell count time curve (AUEC) over the first dosing interval on week 1 from time 0 to the time prior to the second dose (AUEC0 168,w1), AUEC over the second dosing interval on week 2 from time 0 to the time prior to the third dose (AUEC0-168,w2), AUEC over the third dosing interval on week 3 from time 0 to the time prior to the fourth dose (AUEC0-168,w3), AUEC over the fourth dosing interval on week 4 from time 0 to 168 hours post dose (AUEC0-168,w4), AUEC from time 0 on week 1 to the time point on week 12 (AUEC0-w12), AUEC from time 0 on week 1 to the time point on week 28 (AUEC0 w28) for the change from baseline CD19+ B-cell count data. The time-normalized AUEC parameters presented were calculated by dividing the respective AUEC by the time interval used to calculate the AUEC.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    76
    72
    Units: cells/µL
    arithmetic mean (standard deviation)
        AUEC0-168,w1, normalized cells
    -135.0 ( 118.88 )
    -142.1 ( 125.23 )
        AUEC0-168,w2, normalized cells
    -137.1 ( 123.43 )
    -155.1 ( 133.38 )
        AUEC0-168,w3, normalized cells
    -137.1 ( 123.43 )
    -155.1 ( 133.38 )
        AUEC0-168,w4, normalized cells
    -138.7 ( 121.62 )
    -159.2 ( 136.55 )
        AUEC0-w12, normalized cells
    -143.0 ( 121.38 )
    -158.7 ( 133.02 )
    No statistical analyses for this end point

    Secondary: Incidence of Antidrug Antibodies (ADA) & Neutralising Antibody (NAb) by Visit

    		 Close Top of page
    End point title
    		 Incidence of Antidrug Antibodies (ADA) & Neutralising Antibody (NAb) by Visit
    End point description
    Immunogenicity endpoint: incidence of antidrug antibodies (ADA) and Neutralising Antibody (NAb). Immunogenicity sampling was performed pre-dose at Day 1, weeks 2, 3 and 4 and at any time during the visits at weeks 5, 12, 20 and 28
    End point type
    Secondary
    End point timeframe
    Pre-dose on Day 1 to Weeks 5, 12, 20 and 28.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    152
    156
    Units: Number of subjects
        Week 1 (Baseline) ADA negative
    138
    148
        Week 1 (Baseline) ADA positive
    3
    2
        Week 1 (Baseline) NAb negative
    3
    2
        Week 1 (Baseline) NAb positive
    0
    0
        Week 2 ADA negative
    143
    152
        Week 2 ADA positive
    1
    0
        Week 2 NAb negative
    1
    0
        Week 2 NAb positive
    0
    0
        Week 3 ADA negative
    138
    149
        Week 3 ADA positive
    5
    0
        Week 3 NAb negative
    2
    0
        Week 3 NAb positive
    0
    0
        Week 4 ADA negative
    145
    149
        Week 4 ADA positive
    2
    0
        Week 4 NAb negative
    2
    0
        Week 4 NAb positive
    0
    0
        Week 5 ADA negative
    139
    145
        Week 5 ADA positive
    2
    0
        Week 5 NAb negative
    2
    0
        Week 5 NAb positive
    0
    0
        Week 12 ADA negative
    137
    144
        Week 12 ADA positive
    3
    0
        Week 12 NAb negative
    3
    0
        Week 12 NAb positive
    3
    0
        Week 20 ADA negative
    131
    144
        Week 20 ADA positive
    7
    4
        Week 20 NAb negative
    7
    4
        Week 20 NAb positive
    7
    0
        Week 28 ADA negative
    126
    129
        Week 28 ADA positive
    10
    16
        Week 29 NAb negative
    9
    16
        Week 29 NAb positive
    1
    0
    No statistical analyses for this end point

    Secondary: Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time

    		 Close Top of page
    End point title
    		 Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time
    End point description
    Exploratory pharmacodynamic endpoint: Mean (SD) Change from Baseline of Immunoglobulin (IgG) and immunoglobulin M (IgM) (mg/dL) by Scheduled Time for Each Treatment (Safety Analysis Set). Samples for IgG and IgM assessment were collected at Baseline and Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
    End point type
    Secondary
    End point timeframe
    Baseline to Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    157
    158
    Units: Mg/dL
    arithmetic mean (standard deviation)
        IgG Week 2
    -0.21 ( 132.687 )
    -14.79 ( 132.64 )
        IgG Week 3
    -17.08 ( 157.848 )
    -30.04 ( 124.814 )
        IgG Week 4
    -36.31 ( 132.326 )
    -34.64 ( 156.790 )
        IgG Week 5
    -34.62 ( 162.748 )
    -38.21 ( 170.758 )
        IgG Week 12
    -28.15 ( 159.898 )
    -2.30 ( 202.017 )
        IgG Week 20
    -26.86 ( 189.937 )
    -22.40 ( 173.420 )
        IgG Week 28
    -19.33 ( 200.69 )
    8.70 ( 238.309 )
        IgM Week 2
    0.34 ( 18.018 )
    4.60 ( 28.273 )
        IgM Week 3
    0.87 ( 25.092 )
    2.12 ( 32.569 )
        IgM Week 4
    0.64 ( 31.836 )
    0.03 ( 30.009 )
        IgM Week 5
    -1.91 ( 29.521 )
    -2.02 ( 21.771 )
        IgM Week 12
    8.02 ( 37.876 )
    9.12 ( 21.671 )
        IgM Week 20
    -12.94 ( 46.966 )
    -14.35 ( 26.012 )
        IgM Week 28
    -22.08 ( 29.200 )
    -20.85 ( 37.475 )
    No statistical analyses for this end point

    Other pre-specified: Exploratory Analyses of Tumor Response and Time to Event

    		 Close Top of page
    End point title
    		 Exploratory Analyses of Tumor Response and Time to Event
    End point description
    Exploratory Efficacy Endpoint: Analyses of Tumor Response and Time to Event, as Determined by the Combined International Working Group (IWG) Criteria 2014, Lugano Classification and IWG Criteria 2007 (Central Assessment) (Full Analysis Set)
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 0) to Week 28
    End point values
    		 SAIT101 MabThera
    Number of subjects analysed
    157
    158
    Units: Number of subjects
        Complete Response (CR)
    53
    50
        Partial Response (PR)
    47
    55
        Stable Disease (SD)
    21
    25
        Progressive Disease (PD)
    19
    11
        Unknown (UKN)
    1
    2
        No Evidence of Disease (NED)
    4
    1
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    After the participant 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 should be reported.
    Adverse event reporting additional description
    All AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) v22.1. If an AE changed from non-SAE to be an SAE, it was treated as a new event and was counted as 2 events in the AE summary. A treatment-emergent AE (TEAE) was defined as any AE with an onset date on or after the date of the first dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    SAIT101
    Reporting group description
    		 SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3 and 4.

    Reporting group title
    MabThera
    Reporting group description
    		 MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4.

    Serious adverse events
    		 SAIT101 MabThera
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 157 (1.91%)
    4 / 158 (2.53%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 157 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 157 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    1 / 157 (0.64%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 157 (0.64%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Sudden cardiac death
         subjects affected / exposed
    0 / 157 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 157 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cystitis klebsiella
         subjects affected / exposed
    1 / 157 (0.64%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    0 / 157 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 SAIT101 MabThera
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    85 / 157 (54.14%)
    80 / 158 (50.63%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 157 (1.91%)
    4 / 158 (2.53%)
         occurrences all number
    4
    4
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    18 / 157 (11.46%)
    26 / 158 (16.46%)
         occurrences all number
    27
    30
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 157 (2.55%)
    3 / 158 (1.90%)
         occurrences all number
    5
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    9 / 157 (5.73%)
    2 / 158 (1.27%)
         occurrences all number
    10
    5
    Paraesthesia
         subjects affected / exposed
    4 / 157 (2.55%)
    0 / 158 (0.00%)
         occurrences all number
    6
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    7 / 157 (4.46%)
    1 / 158 (0.63%)
         occurrences all number
    7
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 157 (2.55%)
    4 / 158 (2.53%)
         occurrences all number
    4
    4
    Fatigue
         subjects affected / exposed
    6 / 157 (3.82%)
    7 / 158 (4.43%)
         occurrences all number
    6
    11
    Pyrexia
         subjects affected / exposed
    4 / 157 (2.55%)
    2 / 158 (1.27%)
         occurrences all number
    4
    2
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 157 (1.27%)
    4 / 158 (2.53%)
         occurrences all number
    2
    4
    Abdominal pain upper
         subjects affected / exposed
    4 / 157 (2.55%)
    3 / 158 (1.90%)
         occurrences all number
    4
    3
    Diarrhoea
         subjects affected / exposed
    5 / 157 (3.18%)
    5 / 158 (3.16%)
         occurrences all number
    5
    5
    Nausea
         subjects affected / exposed
    6 / 157 (3.82%)
    4 / 158 (2.53%)
         occurrences all number
    7
    4
    Vomiting
         subjects affected / exposed
    1 / 157 (0.64%)
    4 / 158 (2.53%)
         occurrences all number
    1
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 157 (2.55%)
    3 / 158 (1.90%)
         occurrences all number
    4
    3
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    4 / 157 (2.55%)
    8 / 158 (5.06%)
         occurrences all number
    4
    8

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Oct 2016
    Amendment 01 dated 07 October 2016 implemented the following changes: • Revised the criteria of secondary efficacy endpoints; ORR at week 12 was added. • Revised text describing interim analysis. • Revised text for AESI criteria. • Added text in discontinuation of study treatment criteria. • The schedule of assessment table was updated with a few clarifications with regards to bone marrow biopsy, CT scan, possible items for unscheduled visit added. • Footnotes to the schedule of assessment table were updated for diagnostic biopsies, bone marrow biopsy, and PK sampling. • Revisions were made in the inclusion and exclusion criteria text for clarity about archival tissue, lymphoma, and TB. • Criteria for withdrawal from the study were clarified. • Updated the text on unblinding for interim analysis. • Clarified the vital sign parameter for body temperature. • Serious adverse event criteria for infant death was updated. • Updated text for recording, reporting, and follow-up of AEs. • Definition of PPS was updated. • Text was updated for efficacy analyses. • Text was updated for DSMB review.
    27 Jun 2017
    Amendment 02 dated 27 June 2017 implemented the following changes: • Updated the number of Investigators and centers. • Safety and immunogenicity data were added for appropriate interpretation of PK/PD data in interim analysis in PK/PD subpopulation. • Updated the PD endpoint for B-cell recovery. • Time restriction was deleted from premedication criteria. • Summary of study design was updated. • Modified schedule of assessments including footnotes. • Revisions were made in inclusion and exclusion criteria text for clarity. • Re-screening criteria was updated. • Added text for definition of subjects lost to follow-up. • Added text for BSA criteria in treatment administration. • Text was updated for formulation and packaging. • Text for administration of study treatment was updated. • Clarifications were made for anaphylactic reactions. • Text for infusion related reactions was updated. • Clarifications were made for follow-up of AEs. • Appendix 10 was updated time for PK/PD sampling.
    03 Nov 2017
    Amendment 03 dated 03 November 2017 implemented the following changes: • Study design was updated with addition of efficacy in interim analysis. • The PD and safety endpoint were modified. • Immunogenicity assessment criteria were updated. • The sample size for PK/PD endpoint was re-estimated and subject numbers were updated for PK/PD assessments. • Treatment for subjects with progressive disease was added. • Infusion related reactions were clarified further. • The PDS were re-defined. • Interim analysis population was updated. • Reference list was updated

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Apr 28 21:26:52 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA