PK, PD, Safety, and Efficacy of SAIT101 Versus MabThera® Versus Rituxan® in Patients With Rheumatoid Arthritis

• Sponsor: Archigen Biotech Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02819726
• Collaborator: (none)
• Enrollment: 294
• Locations: 75
• Arms: 3
• Actual Duration (Months): 24.9
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

A randomised, double blind, parallel group, multicentre study yo compare the pharmacokinetics, pharmacokinetics, safety and efficacy of SAIT101 versus MabThera® versus Rituxan® in patients with rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: SAIT101; Biological: MabThera; Biological: Rituxan	Phase 1

Detailed Description

This is a randomized, double-blind, parallel group, multicenter study to compare the pharmacokinetics (PK), pharmacodynamics (PD), safety, efficacy, tolerability, and immunogenicity of SAIT101 (biosimilar rituximab) versus MabThera® versus Rituxan® in patients with rheumatoid arthritis (RA). This study will take place globally across approximately 75 study centers in order to randomize approximately 282 patients. The study consists of Part A from baseline for PK and efficacy analysis, followed by Part B from Week 24 to 52 for safety follow-up in which collects transition data.

Study Design

• Study Type: Interventional
• Actual Enrollment: 294 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: In Part A, patients are randomized in a 1:1:1 ratio to receive one course (baseline and Week 2) of SAIT101 (n=94) versus Rituxan® (n=94) versus MabThera® (n=94). At Week 24, patients are evaluated for the second course (Week 24 and 26) of the infusion. In Part B, eligible patients in the SAIT101 arm receive the second course of SAIT101 treatment. Eligible patients in the MabThera® arm receive the second course of MabThera® treatment. Eligible patients in the Rituxan® arm are randomized in a 1:1 ratio to receive SAIT101 or Rituxan® treatment. Patients are followed up for safety until Week 52.In Part A, patients are randomized in a 1:1:1 ratio to receive one course (baseline and Week 2) of SAIT101 (n=94) versus Rituxan® (n=94) versus MabThera® (n=94). At Week 24, patients are evaluated for the second course (Week 24 and 26) of the infusion. In Part B, eligible patients in the SAIT101 arm receive the second course of SAIT101 treatment. Eligible patients in the MabThera® arm receive the second course of MabThera® treatment. Eligible patients in the Rituxan® arm are randomized in a 1:1 ratio to receive SAIT101 or Rituxan® treatment. Patients are followed up for safety until Week 52.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Oct 11, 2016
• Actual Primary Completion Date: Apr 30, 2018
• Actual Study Completion Date: Nov 7, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAIT101 In Part A, each patient will receive one course of two 1000 mg SAIT101 infusions: one on Day 1 and the second on Day 15. In Part B, patients with an inadequate response (<50% improvement from Baseline in swollen and tender joint count at Week 24) will be eligible for a further course of two 1000 mg infusions of SAIT101 on Week 24 and Week 26.	Biological: SAIT101; 1,000 mg i.v. of SAIT101 on Day 1 and 15. 1,000 mg i.v. of SAIT101 on week 24 and 26 for eligible patients.
Active Comparator: Rituxan In Part A, each patient will receive one course of two 1000 mg Rituxan infusions: one on Day 1 and the second on Day 15. In Part B, patients with an inadequate response (<50% improvement from Baseline in swollen and tender joint count at Week 24) will be randomised in a 1:1 ratio to receive Rituxan or SAIT101 10000 mg infusions on Week 24 and Week 26.	Biological: Rituxan; 1,000 mg i.v. of Rituxan® on Day 1 and 15. 1,000 mg i.v. of Rituxan® on week 24 and 26 for eligible patients.; Other Names: Rituximab
Active Comparator: MabThera In Part A, each patient will receive one course of two 1000 mg MabThera infusions: one on Day 1 and the second on Day 15. In Part B, patients with an inadequate response (<50% improvement from Baseline in swollen and tender joint count at Week 24) will be eligible for a further course of two 1000 mg infusions of MabThera on Week 24 and Week 26.	Biological: MabThera; 1,000 mg i.v. of MabThera® on Day 1 and 15. 1,000 mg i.v. of MabThera® on week 24 and 26 for eligible patients.; Other Names: Rituximab

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration Time Cure From Time 0 to Last Quantifiable Concentration (AUC0-t) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Area under the concentration-time curve from time 0 (immediately predose on Day 1) to last quantifiable concentration (AUC0-t). Geometric means by treatment (Pharmacokinetic Analysis Set).

2. Area Under the Plasma Concentration Versus Time Curve (AUC0-∞) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Area Under the Plasma Concentration from time 0 to infinity (AUC0-∞ (infinity). Calculated by linear up/log down trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration divided by the elimination rate constant: AUC(0-last) + C(last)/λz.

3. Area Under the Plasma Concentration Versus Time Curve (AUC0-D15) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Area Under the Concentration verses time from time 0 to Day 15 prior to infusion (AUC0-D15) calculated by linear up/log down trapezoidal summation. Actual time/concentration on Day 15 was used for the calculation of this parameter unless the parameter was derived by interpolation.

4. Peak Plasma Concentration (Cmax) After Day 15 Infusion [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1 and 2 (Pre-dose 2). Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Maximum Plasma Concentration (Cmax) after Day 15 infusion (Dose 2)

5. Trough Concentration (Ctrough) Before the Second Infusion on Day 15 [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1 and 2 (Pre-dose 2). Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Trough concentration (Ctrough) before the second infusion on Day 15 (Dose 2). Trough (pre-dose) concentration prior to second infusion on Day 15 obtained directly from the observed concentration versus time data.

6. Change From Baseline in DAS28-CRP at Week 24 [Baseline and Week 24]

   Disease Activity Score 28 C-reactive protein score (DAS28-CRP) at Week 24 (Full Analysis Set). CRP samples were collected at Baseline and Weeks 8, 16 and 24. 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. Total DAS28-CRP scores were calculates and range from 2.0 (minimum) to 10 (maximum). Lower scores represent a better patient outcome. Disease remission is considered achieved if the score is between 0 and <2.6. Low disease activity corresponds to 2.6 to <3.2. Moderate activity is between 3.2 & ≤5.1, while high activity is above 5.1.

Secondary Outcome Measures

1. Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Area under the concentration time curve week 2 to week 24 (AUC(w2-24) calculated by linear up/log down trapezoidal summation.

2. Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12)) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8 and 12. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Area under the concentration time curve Day 0 to Week 12 calculated by linear up/log down trapezoidal summation.

3. Time to Maximum Plasma Concentration (Tmax) (Dose 1) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Maximum plasma concentration over the first dosing interval obtained directly from the observed concentration versus time data.

4. Time to Maximum Plasma Concentration (Tmax) (Dose 2) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Time of maximum concentration postinfusion over the second dosing interval, obtained directly from the observed concentration versus time data.

5. Apparent Terminal Rate Constant (λz) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Apparent terminal rate constant (λz) determined by linear regression of the terminal points of the log-linear concentration-time curve. Best fit method followed by visual assessment was used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points was used for determination.

6. Systemic Clearance (CL) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Systemic clearance (CL) over the first dosing period calculated as dose (first + second dose) divided by AUC(0-∞).

7. Volume of Distribution (VD) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Volume of distribution (VD) over the first dosing period calculated as dose (first + second dose) divided by [λz AUC(0-∞)]

8. Terminal Half-life (T1/2) [Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacokinetic endpoint: Terminal half-life determined as ln2/λz.

9. Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

   Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) samples taken at Baseline and Weeks 8, 16, 24, 36 and 52. 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. Total DAS28-CRP scores are presented and range from 2.0 (minimum) to 10 (maximum). Lower scores represent a better patient outcome. Disease remission is considered achieved if the score is between 0 and <2.6. Low disease activity corresponds to 2.6 to <3.2. Moderate activity is between 3.2 & ≤5.1, while high activity is above 5.1.

10. American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    American Collage of Rheumatology (ACR) 20% response criteria (ACR20) response rates were assessed at Baseline and Weeks 8, 16, 24, 36 and 52. An ACR20 response is defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [Health Assessment Questionnaire (HAQ)], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

11. 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 [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    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. An ACR50 response is defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [Health Assessment Questionnaire (HAQ)], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). An ACR70 response is defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [Health Assessment Questionnaire (HAQ)], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

12. 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) [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    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.

13. 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]) [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    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.

14. 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]) [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS]). Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS]) where 0 = no pain and 100 = severe pain.

15. 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) [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    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 visual analogue scale [VAS]). Patients rate how their Rheumatoid Arthritis has affected them, where 0 = very well and 100 = very poor.

16. 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]) [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    the Health Assessment Questionnaire-Disability Index (HAQ-DI) contains 20 questions split into 8 categories (dressing & grooming, arising, eating, walking, hygiene, reach, grip & activities). Scores were: 0 = Without ANY Difficulty; 1 = With SOME Difficulty; 2 = With MUCH Difficulty; 3 = UNABLE to Do. Total scores were calculated as the summed category scores divided by the number of categories. Total HAQ-DI scores are presented which range from 0 to 3. Higher scores represent a worse outcome. Scores of 0 to 1 represent mild to moderate difficulty, 1 to 2 moderate disability, and 2 to 3 severe to very severe disability.

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

    C-reactive protein (CRP) level (Mg/L). CRP is a marker for inflammation. a normal reading is <3 Mg/L. Higher values indicate disease related inflammation and increased cardiovascular risk. CRP levels between 3 Mg/L and 10 Mg/L are mildly elevated. Levels between 10 Mg/L and 100 Mg/L are moderately elevated and CRP levels above 100 Mg/L are severely elevated.

18. Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    Disease Activity Score 28- Erythrocyte Sedimentation Rate (DAS28-ESR) consisted of tender joint counts (TJC), swollen joint counts (SJC) & erythrocyte sedimentation rate (ESR). The formula is: [0.56*SQRT(tender 28 joint count)+0.28*SQRT(swollen 28 joint count)+0.7*ln(ESR)]+0.014*patient global health assessment. Total DAS28-ESR scores are presented. Total scores range from 2 (minimum) to 10 (maximum). A lower score represents a better patient outcome. A DAS28-ESR of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission.

19. Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    Efficacy endpoint: number of participants with a major clinical response defined as a continuous ACR70 from Baseline (Day 1) for at least 24 weeks. ACR70 is a measure based on American College of Rheumatology criteria of at least a 70% improvement in the number of tender and swollen joints, and a 70% improvement in at least 3 of the following: the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function measured using the Stanford Health Assessment Questionnaire the physician's global assessment of disease status; serum C-reactive protein levels.

20. Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    Number if Participants with a Clinical Remission Response (CRR) defined by the Simplified Disease Activity Index (SDAI) <3.3 at weeks 8, 16, 24, 36 and 52 (EOS).

21. Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 [Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)]

    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.

22. Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) [Baseline (Day 1) and Weeks 8, 16, 24, 36 and 52 (EOS)]

    Change from baseline (Day 1) in immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) levels (mg/dL) at Week 8, 16, 24 36 and 52 (End of study)

Other Outcome Measures

1. Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24 [Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   Pharmacodynamic endpoint: proportion of participants (n) with depletion of CD19+ B-cell count up to week 24 (Pharmacodynamic analysis set).

2. Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion [Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.]

   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).

3. Pharmacodynamic Endpoint: Duration of CD19+ B-cell Depletion [Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.]

   Duration of CD19+ B-cell depletion (only participants that returned to non-depletion at or before week 24 were included)

4. Pharmacodynamic Endpoint: Number of Participants With CD19+ B-cell Count Recover Versus Baseline [Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.]

   Number of participants with CD19+ B-cell count recover versus baseline. Incidence of B-Cell recovery was defined as either CD19+ B-cell counts retuned to baseline or the lower limit or normal of 110 cells/µL at week 24).

5. Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24 [Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.]

   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

6. Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period [Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.]

   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])

7. Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 [Baseline (Day 1) and Weeks 8, 16, 24, 26 & 52 (EOS)]

   Pharmacodynamic endpoint: Change from baseline (Day 1) in C-reactive protein (CRP) levels (mg/dL) at weeks 8, 16, 24, 36 and 52 (EOS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Severe RA defined as:

• Diagnosis of RA according to the revised (1987) American College of Rheumatology (ACR) criteria for the classification of RA for at least 3 months prior to screening visit (see Appendix 3).

• And ≥6 swollen joints and ≥6 tender/painful joints (from the 66/68 joint count system).

• And C-reactive protein (CRP) ≥1.0 mg/dL or an erythrocyte sedimentation rate (ESR) ≥28 mm/hour at Screening.

• And positive rheumatoid factor (RF) (≥20 units/mL) or anti cyclic citrullinase peptide (CCP) antibodies (≥10 units/mL) at Screening.

1. Patients with severe RA who have had an inadequate response to at least 3 months' treatment (according to the approved treatment and dosage) or intolerance (at Investigator's discretion and/or experience of intolerable AE or toxicity such as infusion related reaction, hypersensitivity, anaphylaxis or severe toxicity) to anti-tumour necrosis factor (TNF) therapy (experience of severe adverse event (AE) or toxicity).

2. Current treatment for RA on an outpatient basis:

• Receiving methotrexate (MTX) 7.5 - 25mg/week (oral or parenteral) for at least 12 weeks, including the last 4 weeks prior to Day 1 at a stable dose, via the same route of administration, dose, and formulation. Patients receiving a lower dose of MTX (<10 mg/week), stable for 4 weeks prior to Day 1, should be doing so as a result of a documented evidence of intolerance to higher doses of MTX.

Exclusion Criteria:

1. Females who are pregnant, breastfeeding, or planning a pregnancy during the Treatment Period of and 12 months after the last infusion of study drug.

2. Class IV as per the Classification of Global Functional Status in Rheumatoid Arthritis (as per ACR 1991 Revised Criteria) (see Appendix 4) or wheelchair/bed bound.

3. History of or current inflammatory joint disease other than RA (including but not limited to gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy or Lyme disease).

4. History of or current systemic autoimmune disorder (including but not limited to systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, Felty syndrome, scleroderma, inflammatory myopathy, fibromyalgia, juvenile idiopathic arthritis, mixed connective tissue disease, vasculitis or other overlap syndrome), with the exception of the secondary Sjögren's syndrome.

5. Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening.

6. History of opportunistic infection.

7. History of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis) and infected prosthetic joint.

8. Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. anti infective agents within 4 weeks prior to Screening or oral anti-infective agents within 2 weeks prior to Screening or use of antibiotic therapy three or more times in the last six months prior to Screening

9. Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology.

• Patients with a negative HBsAg and positive HBcAb must have a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level <20 IU/mL (or 112 copies/mL) by polymerase chain reaction (PCR). These HBV patients must be willing to undergo monthly PCR HBV DNA testing during treatment and may participate following consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, and provided they agree to receive treatment as indicated. An HBV re-test will be performed monthly including Day 1, Weeks 4, 8, 12, 16, 20, 24, 36, 52, and unscheduled visit if required.

• Patients with a positive test because of HBV vaccine may be included (i.e., anti-HBs+ and anti HBc-).

• Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV ribonucleic acid (RNA).

1. Confirmed current active tuberculosis (TB). • Patients with latent TB as determined by positive QuantiFERON-TB test may be enrolled if such patients have written confirmation from health care provider (e.g., Pulmonologist or Infection Specialist) of adequate prophylaxis before or within the screening period and no evidence of tuberculosis on a chest X-ray performed within 3 months from Day 1.

• Screening period can be extended to 60 days for prophylaxis of latent TB.

• QuantiFERON-TB test can be re-tested, if inconclusive.

1. Any significant cardiac disease (e.g., coronary artery disease with unstable angina, coronary heart failure New York Heart Association Class III and IV, familial long QT syndrome, uncontrolled cardiac disease).

2. History of moderate to severe chronic obstructive pulmonary disease (COPD) and/or history of severe COPD exacerbation(s) within the last 12 months of Screening.

3. Vaccination with live or attenuated vaccines within 6 weeks prior to first dose of study drug or planned administration during study participation or within 4 weeks following last dose of study drug. Treatment with IV Gamma Globulin or the Prosorba® Column within 6 months prior to Day 1.

4. History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the study drug including known hypersensitivity or allergy to a murine product.

5. Hypogammaglobulinemia at screening (Immunoglobulin G (IgG) <600 mg/dL).

6. Patients with hemoglobin <8.5 g/dL, absolute neutrophil count (ANC) <1,500 cells/µL or platelet count <75,000 cells/µL at Screening. If a patient has findings marginally below this limit, re testing is allowed, at the Investigator's discretion, within the 30 day period between Visit 1 and Visit 2.

• Creatinine clearance < 50 mL/min (Cockcroft-Gault formula)

• Liver function: Total bilirubin >2.0 mg/dL (>34 µmol/L) except for patients with Gilbert's Syndrome or hemolysis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 × upper limit of normal (ULN). Patients with total bilirubin >2.0 mg/dL possibly due to Gilbert's Syndrome should have a direct bilirubin checked. If the direct bilirubin is normal and medical history is suggestive/positive for Gilbert's Syndrome, the patient successfully meets the criteria.

The AST and ALT may be repeated once within the Screening period if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion.

1. History of cancer within the last 5 years prior to Screening, treated with anti-cancer chemotherapy, including solid tumors and hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that have been excised and cured).

2. Major surgical procedure within 4 weeks prior to or planned within 24 weeks of Day 1, with the exception of surgical procedures for dental prosthesis.

3. Previous treatment with a B cell modulating or B cell depletion therapy, such as, but not limited to rituximab, belimumab, atacicept, tabalumab, ocrelizumab, ofatumumab, obinutuzumab, epratuzumab and other experimental treatments.

4. Injectable corticosteroids within 6 weeks prior to Day 1.

5. Participation in a previous clinical study within 4 weeks of Screening or having received treatment with a drug that has not received regulatory approval for any indication within a minimum of 5 half-lives prior to Day 1.

6. Patients who, based on the Investigator's judgment, have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Conditions may also include cardiovascular, vascular, pulmonary, hepatic, renal, endocrine or neurological conditions as determined by medical history, physical examination, laboratory tests or electrocardiogram (ECG).

7. Patients who, in the judgment of the Investigator, are likely to be non-compliant or uncooperative during the study.

8. History of substance abuse (alcohol or drug).

9. History of demyelinating disorders (such as multiple sclerosis or Guillain-Barré syndrome).

10. Patients at risk of progressive multifocal leukoencephalopathy (PML):

• Patients with immune deficiency such as transplant patients on immunosuppressive medications

• Patients receiving certain kinds of chemotherapy

• Patients receiving natalizumab (Tysabri®) for multiple sclerosis

• Patients with psoriasis on longer term efalizumab (Raptiva®) or patients with acquired immunodeficiency syndrome (AIDS)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Anniston	Alabama	United States	36207
2	Research Site	El Cajon	California	United States	92020
3	Research Site	La Mesa	California	United States	91942
4	Research Site	Lakewood	California	United States	90712
5	Research Site-1	Los Angeles	California	United States	90017
6	Research Site-2	Los Angeles	California	United States	90017
7	Research Site	San Leandro	California	United States	94578
8	Research Site	Orlando	Florida	United States	32804
9	Research Site	Tampa	Florida	United States	33612
10	Research Site	Tampa	Florida	United States	33613
11	Research Site	Boise	Idaho	United States	83642
12	Research Site	Kansas City	Kansas	United States	66160
13	Research Site	Lansing	Michigan	United States	48917
14	Research Site	Waco	Texas	United States	76710
15	Research Site	Tacoma	Washington	United States	98405
16	Research Site	Mostar		Bosnia and Herzegovina	88000
17	Research site	Sarajevo		Bosnia and Herzegovina	71000
18	Research Site-1	Plovdiv		Bulgaria	4002
19	Research Site-2	Plovdiv		Bulgaria	4002
20	Research Site	Sofia		Bulgaria	1336
21	Research Site	Sofia		Bulgaria	1612
22	Research site	Brno		Czechia	656 91
23	Research site	Ostrava		Czechia	702 00
24	Research site	Praha 2		Czechia	128 50
25	Research site	Uherské Hradiště		Czechia	686 01
26	Research site	Bad Doberan	Mecklegurg-Vorpommern	Germany	18209
27	Research site	Ratingen	Nordrhein-Westfalen	Germany	40882
28	Research site	Vogelsang	Sachsen-Anhalt	Germany	39245
29	Research site	Dresden	Sachsen	Germany	01067
30	Research site	Hamburg		Germany	22143
31	Research site	Rendsburg		Germany	24768
32	Research Site	Budapest		Hungary	1027
33	Research Site	Budapest		Hungary	1083
34	Research site	Bangalore	Karnataka	India	560054
35	Research site	Hubli	Karnataka	India	580021
36	Research site	Pune	Maharashtra	India	411001
37	Research site	Pune	Maharashtra	India	411005
38	Research site	Pune	Maharashtra	India	411007
39	Research site	Bīkaner	Rajasthan	India	334003
40	Research site	Jaipur	Rajasthan	India	302001
41	Research site	Kolkata	West Bengal	India	700107
42	Research Site	Anyang		Korea, Republic of	14068
43	Research Site	Busan		Korea, Republic of	49201
44	Research Site	Busan		Korea, Republic of	49241
45	Research Site	Daegu		Korea, Republic of	41944
46	Research Site	Daegu		Korea, Republic of	42472
47	Research Site	Daejeon		Korea, Republic of	35015
48	Research Site	Gwangju		Korea, Republic of	61469
49	Research Site	Jeju		Korea, Republic of	63241
50	Research Site	Seoul		Korea, Republic of	03080
51	Research Site	Seoul		Korea, Republic of	04763
52	Research Site	Seoul		Korea, Republic of	07061
53	Research Site	Suwon		Korea, Republic of	16247
54	Research Site	Durango		Mexico	34000
55	Research Site	Mexico City		Mexico	06700
56	Research Site	Mexico City		Mexico	07020
57	Research site	Gdańsk		Poland	80-952
58	Research site	Kraków		Poland	30-033
59	Research site	Kraków		Poland	30-363
60	Research site	Kłodzko		Poland	57-300
61	Research site	Nowa Sól		Poland	67-100
62	Research site	Oświęcim		Poland	32-600
63	Research site	Poznań		Poland	60-773
64	Research site	Poznań		Poland	61-113
65	Research site	Tychy		Poland	43-100
66	Research site	Warszawa		Poland	00-660
67	Research site	Warszawa		Poland	03-291
68	Research site	Wrocław		Poland	51-128
69	Research site	Zamość		Poland	22-400
70	Research Site	Fuenlabrada		Spain	28942
71	Research Site	La Coruña		Spain	15006
72	Research Site	La Coruña		Spain	15702
73	Research Site	La Coruña		Spain	15706
74	Research Site	Sevilla		Spain	41010
75	Research Site	Sevilla		Spain	41014

Sponsors and Collaborators

• Archigen Biotech Limited

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 27, 2017
• Statistical Analysis Plan - Feb 13, 2019

More Information

Publications

None provided.

• Responsible Party: Archigen Biotech Limited
• ClinicalTrials.gov Identifier: NCT02819726
• Other Study ID Numbers: AGB001
• First Posted: Jun 30, 2016
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Archigen Biotech Limited: an inadequate response to anti -TNF therapy
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Rituximab

Study Results

Participant Flow

Recruitment Details	This was a global study conducted in 66 study centres. The first participant entered the study on 11 October 2016 and the date of the last participants last study visit was 07 November 2018.

Arm/Group Title	SAIT101 (Part A and B)	MabThera (Part A and B)	Rituxan (Part A and B)	SAIT101 (Part B Only)
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants	1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,
Period Title: Part A (All Participants)
STARTED	98	98	98	0
COMPLETED	92	88	87	0
NOT COMPLETED	6	10	11	0
Period Title: Part A (All Participants)
STARTED	73	70	39	38
COMPLETED	70	68	35	36
NOT COMPLETED	3	2	4	2

Baseline Characteristics

Arm/Group Title	SAIT101	MabThera	Rituxan	Total
Arm/Group Description	SAIT101: 1,000 mg i.v. of SAIT101 on Day 1 and 15. 1,000 mg i.v. of SAIT101 on week 24 and 26 for eligible participants.	MabThera: 1,000 mg i.v. of MabThera® on Day 1 and 15. 1,000 mg i.v. of MabThera® on week 24 and 26 for eligible participants.	Rituxan: 1,000 mg i.v. of Rituxan® on Day 1 and 15. 1,000 mg i.v. of Rituxan® on week 24 and 26 for eligible participants.	Total of all reporting groups
Overall Participants	98	98	98	294
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.9 (12.41)	52.5 (10.87)	52.1 (12.09)	51.8 (11.79)
Age, Customized (Count of Participants)
18-60 years	76 77.6%	75 76.5%	71 72.4%	222 75.5%
>60 years	22 22.4%	23 23.5%	27 27.6%	72 24.5%
Sex: Female, Male (Count of Participants)
Female	79 80.6%	81 82.7%	80 81.6%	240 81.6%
Male	19 19.4%	17 17.3%	18 18.4%	54 18.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	30 30.6%	30 30.6%	29 29.6%	89 30.3%
Not Hispanic or Latino	68 69.4%	68 69.4%	69 70.4%	205 69.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	24 24.5%	20 20.4%	21 21.4%	65 22.1%
Asian	18 18.4%	19 19.4%	24 24.5%	61 20.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 2%	0 0%	1 1%	3 1%
White	52 53.1%	56 57.1%	52 53.1%	160 54.4%
More than one race	2 2%	3 3.1%	0 0%	5 1.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
South Korea	5 5.1%	3 3.1%	6 6.1%	14 4.8%
Hungary	3 3.1%	0 0%	4 4.1%	7 2.4%
Czechia	7 7.1%	3 3.1%	2 2%	12 4.1%
United States	9 9.2%	13 13.3%	6 6.1%	28 9.5%
Poland	15 15.3%	19 19.4%	23 23.5%	57 19.4%
Mexico	27 27.6%	21 21.4%	21 21.4%	69 23.5%
Bulgaria	4 4.1%	5 5.1%	4 4.1%	13 4.4%
Bosnia and Herzegovina	4 4.1%	3 3.1%	1 1%	7 2.4%
Germany	2 2%	3 3.1%	2 2%	8 2.7%
India	13 13.3%	16 16.3%	17 17.3%	46 15.6%
Spain	9 9.2%	12 12.2%	12 12.2%	33 11.2%
Disease duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.8 (6.73)	11.2 (7.72)	9.3 (7.10)	10.1 (7.22)
C-reactive protein (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	19.5 (28.99)	15.3 (20.63)	16.2 (17.91)	17.0 (2.99)
Erythrocyte sedimentation rate (mm/hr) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm/hr]	51.0 (26.58)	47.5 (22.87)	51.5 (23.35)	50.0 (24.31)
Swollen Joint Count (SJC66) (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	15.2 (7.97)	15.2 (7.01)	13.0 (6.19)	14.5 (7.14)
Tender Joint Count (TJC68) (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	21.7 (11.08)	22.6 (13.66)	20.0 (10.84)	21.4 (11.93)
Patient Global Assessments Visual Analogue Scale (VAS) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	68.9 (15.87)	67.6 (17.53)	70.8 (17.04)	69.1 (16.82)
Physician Global Assessment VAS Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	71.0 (14.3)	69.4 (15.9)	69.8 (14.32)	70.1 (14.51)
Patient Pain Assessment VAS Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	67.0 (18.71)	68.8 (20.02)	70.7 (19.06)	68.8 (19.27)
Health Assessment Questionnaire Disability Index (HAQ-DI) Score (Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score]	1.7 (0.57)	1.7 (0.64)	1.6 (0.64)	1.7 (0.62)
Disease activity score based on a 28-joint count-C-Reactive Protein (DAS-28-CRP( (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.28 (0.890)	5.29 (0.807)	5.17 (0833)	5.25 (0.843)
Disease activity score based on a 28-joint count - Erythrocyte sedimentation Rate (DAS28-ESR) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.54 (0.844)	6.53 (0.781)	6.48 (0.758)	6.52 (0.793)
Anti-drug Antibody (ADA) Status Positive (Count of Participants)
Count of Participants [Participants]	2 2%	1 1%	4 4.1%	7 2.4%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	162.6 (9.29)	161.3 (8.79)	163.3 (8.37)	162.4 (8.83)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	73.0 (17.62)	71.9 (16.94)	71.6 (17.99)	72.2 (17.47)
Body Mass Index (BMI) (Kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg/m^2]	27.5 (5.48)	27.5 (5.46)	26.7 (5.95)	27.2 (5.63)

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration Time Cure From Time 0 to Last Quantifiable Concentration (AUC0-t)
Description	Pharmacokinetic endpoint: Area under the concentration-time curve from time 0 (immediately predose on Day 1) to last quantifiable concentration (AUC0-t). Geometric means by treatment (Pharmacokinetic Analysis Set).
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. (AUC(0-t) could not be determined for 15 participants in the SAIT101 arm, 23 participants in the MabThera arm and 17 in the Rituxan arm as the Week 24 sample was either collected post-dose (i.e. not evaluable), was out of the collection window or was missing.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	79	70	76
Geometric Mean (Geometric Coefficient of Variation) [h*µg/mL]	144500 (34.2)	151600 (33.2)	154600 (35.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model (ANOVA) with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ration
	Estimated Value	95.33
	Confidence Interval	(2-Sided) 90%; 87.07 to 104.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	93.43
	Confidence Interval	(2-Sided) 90%; 85.54 to 102.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model (ANOVA) with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	98.06
	Confidence Interval	(2-Sided) 90%; 89.49 to 107.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve (AUC0-∞)
Description	Pharmacokinetic endpoint: Area Under the Plasma Concentration from time 0 to infinity (AUC0-∞ (infinity). Calculated by linear up/log down trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration divided by the elimination rate constant: AUC(0-last) + C(last)/λz.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. AUC0-∞ could not be calculated for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 2 participants in the Rituxan arm as either the terminal phase was undetermined, the samples were missing or the Regulatory Scientific Quality (RSQ) was <0.800.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	91	91
Geometric Mean (Geometric Coefficient of Variation) [h*µg/mL]	152300 (34.6)	161900 (32.2)	161300 (33.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	94.07
	Confidence Interval	(2-Sided) 90%; 86.91 to 101.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ration
	Estimated Value	94.39
	Confidence Interval	(2-Sided) 90%; 87.21 to 102.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	100.35
	Confidence Interval	(2-Sided) 90%; 92.68 to 108.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve (AUC0-D15)
Description	Pharmacokinetic endpoint: Area Under the Concentration verses time from time 0 to Day 15 prior to infusion (AUC0-D15) calculated by linear up/log down trapezoidal summation. Actual time/concentration on Day 15 was used for the calculation of this parameter unless the parameter was derived by interpolation.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. AUC0-D15 could not be determined for 3 participants in the SAIT101 arm, 5 participants in the MabThera arm and 10 participants in the Rituxan arm as either the 336-hours blood sample was collected <312 hours or samples were missing.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	91	88	83
Geometric Mean (Geometric Coefficient of Variation) [h*µg/mL]	42950 (26.7)	44600 (25.6)	43540 (24.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	96.31
	Confidence Interval	(2-Sided) 90%; 90.52 to 102.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	98.65
	Confidence Interval	(2-Sided) 90%; 92.64 to 105.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	102.43
	Confidence Interval	(2-Sided) 90%; 96.14 to 109.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Peak Plasma Concentration (Cmax) After Day 15 Infusion
Description	Pharmacokinetic endpoint: Maximum Plasma Concentration (Cmax) after Day 15 infusion (Dose 2)
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1 and 2 (Pre-dose 2). Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	94	93	93
Geometric Mean (Geometric Coefficient of Variation) [µg/mL]	406.0 (28.3)	427.7 (28.3)	411.1 (24.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	94.93
	Confidence Interval	(2-Sided) 90%; 89.03 to 101.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	98.75
	Confidence Interval	(2-Sided) 90%; 92.61 to 105.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	104.03
	Confidence Interval	(2-Sided) 90%; 97.54 to 110.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Trough Concentration (Ctrough) Before the Second Infusion on Day 15
Description	Pharmacokinetic endpoint: Trough concentration (Ctrough) before the second infusion on Day 15 (Dose 2). Trough (pre-dose) concentration prior to second infusion on Day 15 obtained directly from the observed concentration versus time data.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1 and 2 (Pre-dose 2). Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. Ctrough could not be determined for 11 participants in the SAIT101 arm, 12 participants in the MabThera arm and 16 participants in the Rituxan arm as samples were collected outside of a 312 to 360 hour window.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	83	81	77
Geometric Mean (Geometric Coefficient of Variation) [µg/mL]	60.35 (40.3)	67.75 (36.2)	58.84 (97.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	89.08
	Confidence Interval	(2-Sided) 90%; 77.20 to 102.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	102.56
	Confidence Interval	(2-Sided) 90%; 88.72 to 118.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment
	Type of Statistical Test	Equivalence
	Comments	Standard acceptance limits for bioequivalence (80.00% to 125.00%) for all treatment comparisons
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	115.13
	Confidence Interval	(2-Sided) 90%; 99.51 to 133.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Change From Baseline in DAS28-CRP at Week 24
Description	Disease Activity Score 28 C-reactive protein score (DAS28-CRP) at Week 24 (Full Analysis Set). CRP samples were collected at Baseline and Weeks 8, 16 and 24. 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. Total DAS28-CRP scores were calculates and range from 2.0 (minimum) to 10 (maximum). Lower scores represent a better patient outcome. Disease remission is considered achieved if the score is between 0 and <2.6. Low disease activity corresponds to 2.6 to <3.2. Moderate activity is between 3.2 & ≤5.1, while high activity is above 5.1.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	91	87	85
Mean (Standard Deviation) [Score on a scale]	-0.991 (1.1735)	-0.832 (0.8483)	-0.861 (0.9488)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	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
	Type of Statistical Test	Equivalence
	Comments	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 Test of Hypothesis	p-Value	0.2402
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.422 to 0.106
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.134
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Least square means and 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
	Type of Statistical Test	Equivalence
	Comments	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 Test of Hypothesis	p-Value	0.1346
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.469 to 0.063
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.135
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Least square means and 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
	Type of Statistical Test	Equivalence
	Comments	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 Test of Hypothesis	p-Value	0.7429
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.314 to 0.224
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.137
	Estimation Comments

7. Secondary Outcome

Title	Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24)
Description	Pharmacokinetic endpoint: Area under the concentration time curve week 2 to week 24 (AUC(w2-24) calculated by linear up/log down trapezoidal summation.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. AUC0-w24 could not be determined for 30 participants in the SAIT101 arm, 32 participants in the MabThera arm and 28 participants either in the Rituxan arm as either there was no concentration at the start and/or end time, the Week 24 sample was out of window or samples were missing.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	64	61	65
Geometric Mean (Geometric Coefficient of Variation) [h*µg/mL]	107300 (41.1)	109200 (40.0)	116000 (40.2)

8. Secondary Outcome

Title	Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12))
Description	Pharmacokinetic endpoint: Area under the concentration time curve Day 0 to Week 12 calculated by linear up/log down trapezoidal summation.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8 and 12. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. AUC0-w12 could not be determined for 1 participant in the SAIT101 arm, 4 participants in the MabThera arm and 1 participant in the Rituxan arm because samples were missing

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	89	92
Geometric Mean (Geometric Coefficient of Variation) [h*µg/mL]	148500 (33.1)	157400 (30.3)	155900 (33.1)

9. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) (Dose 1)
Description	Pharmacokinetic endpoint: Maximum plasma concentration over the first dosing interval obtained directly from the observed concentration versus time data.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. Tmax (dose 1) could not be determined for 1 participant in the SAIT101 arm, 1 patient in the MabThera arm and 2 participants in the Rituxan arm as samples were missing or set to missing due to initial or embedded Below the Limit of Quantification (BLQ)..

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	92	91
Median (Inter-Quartile Range) [Hours]	5.167	5.167	4.500

10. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) (Dose 2)
Description	Time of maximum concentration postinfusion over the second dosing interval, obtained directly from the observed concentration versus time data.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	94	93	93
Median (Inter-Quartile Range) [Hours]	4.167	4.167	4.250

11. Secondary Outcome

Title	Apparent Terminal Rate Constant (λz)
Description	Pharmacokinetic endpoint: Apparent terminal rate constant (λz) determined by linear regression of the terminal points of the log-linear concentration-time curve. Best fit method followed by visual assessment was used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points was used for determination.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. λz could not be determined for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 1 participant in the Rituxan arm as either the terminal phase was undetermined or the Regulatory Scientific Quality (RSQ) was <0.800.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	91	92
Mean (Standard Deviation) [1/hr]	0.002358 (0.00061132)	0.002283 (0.00067311)	0.002240 (0.00059435)

12. Secondary Outcome

Title	Systemic Clearance (CL)
Description	Pharmacokinetic endpoint: Systemic clearance (CL) over the first dosing period calculated as dose (first + second dose) divided by AUC(0-∞).
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. CL could not be determined for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 2 participants in the Rituxan arm as either the terminal phase was undetermined or the Regulatory Scientific Quality (RSQ) was <0.800.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	91	91
Geometric Mean (Geometric Coefficient of Variation) [L/day]	0.01314 (34.6)	0.01235 (29.0)	0.01240 (33.3)

13. Secondary Outcome

Title	Volume of Distribution (VD)
Description	Pharmacokinetic endpoint: Volume of distribution (VD) over the first dosing period calculated as dose (first + second dose) divided by [λz AUC(0-∞)]
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. VD could not be determined for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 2 participants in the Rituxan arm as either the terminal phase was undetermined or the Regulatory Scientific Quality was <0.800.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	91	91
Geometric Mean (Geometric Coefficient of Variation) [Litres (L)]	5.757 (28.0)	5.635 (23.6)	5.727 (22.9)

14. Secondary Outcome

Title	Terminal Half-life (T1/2)
Description	Pharmacokinetic endpoint: Terminal half-life determined as ln2/λz.
Time Frame	Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set. T1/2 could not be determined for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 1 participant in the Rituxan arm as either the terminal was undetermined or the Regulatory Scientific Quality was <0.800.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	91	92
Geometric Mean (Geometric Coefficient of Variation) [Hours]	303.7 (26.1)	316.1 (29.0)	319.7 (26.2)

15. Secondary Outcome

Title	Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52
Description	Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) samples taken at Baseline and Weeks 8, 16, 24, 36 and 52. 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. Total DAS28-CRP scores are presented and range from 2.0 (minimum) to 10 (maximum). Lower scores represent a better patient outcome. Disease remission is considered achieved if the score is between 0 and <2.6. Low disease activity corresponds to 2.6 to <3.2. Moderate activity is between 3.2 & ≤5.1, while high activity is above 5.1.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	97	98
Day 1 (Baseline)	5.282 (0.8899)	5.288 (0.8073)	5.170 (0.8326)
Week 8	4.405 (1.0189)	4.324 (1.1132)	4.251 (1.1392)
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 (End of Study(	3.660 (1.2636)	3.754 (1.3037)	3.518 (1.1276)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6068
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.428 to 0.250
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.172
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5990
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.249 to 0.430
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.172
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 53 (EOS) MabThera vs Rituxan. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3053
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -0.165 to 0.532
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.175
	Estimation Comments

16. Secondary Outcome

Title	American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52
Description	American Collage of Rheumatology (ACR) 20% response criteria (ACR20) response rates were assessed at Baseline and Weeks 8, 16, 24, 36 and 52. An ACR20 response is defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [Health Assessment Questionnaire (HAQ)], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
ACR20 Week 8	39 39.8%	33 33.7%	44 44.9%
ACR20 Week 16	50 51%	54 55.1%	53 54.1%
ACR20 Week 24	36 36.7%	31 31.6%	34 34.7%
ACR20 Week 36	63 64.3%	47 48%	58 59.2%
ACR20 Week 52 (EOS)	60 61.2%	49 50%	59 60.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	9.4
	Confidence Interval	(2-Sided) 95%; -4.74 to 23.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.22
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -15.95 to 11.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.05
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-11.8
	Confidence Interval	(2-Sided) 95%; -25.47 to 2.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.26
	Estimation Comments

17. Secondary Outcome

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
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. An ACR50 response is defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [Health Assessment Questionnaire (HAQ)], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). An ACR70 response is defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [Health Assessment Questionnaire (HAQ)], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
ACR50 Week 8	13 13.3%	11 11.2%	14 14.3%
ACR70 Week 8	2 2%	2 2%	2 2%
ACR50 Week 16	17 17.3%	16 16.3%	14 14.3%
ACR70 Week 16	9 9.2%	4 4.1%	5 5.1%
ACR50 Week 24	15 15.3%	8 8.2%	5 5.1%
ACR70 Week 24	8 8.2%	2 2%	3 3.1%
ACR50 Week 36	37 37.8%	19 19.4%	25 25.5%
ACR70 Week 36	19 19.4%	6 6.1%	12 12.2%
ACR50 Week 52 (EOS)	35 35.7%	25 25.5%	30 30.6%
ACR70 Week 52 (EOS)	23 23.5%	13 13.3%	17 17.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	ACR20 Week 52 (EOS) assessment. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; -4.07 to 22.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.87
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	ACR50 Week 52 (EOS) assessment. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; -10.22 to 17.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.07
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	ACR50 Week 52 (EOS) assessment. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-5.9
	Confidence Interval	(2-Sided) 95%; -19.10 to 7.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.88
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	ACR70 Week 52 (EOS) assessment. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	10.0
	Confidence Interval	(2-Sided) 95%; -1.52 to 21.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.78
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	ACR70 Week 52 (EOS) assessment. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	5.4
	Confidence Interval	(2-Sided) 95%; -6.69 to 17.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.08
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	ACR70 Week 52 (EOS) assessment. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 92%; -15.68 to 6.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.58
	Estimation Comments

18. Secondary Outcome

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)
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.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
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 16	6.5 (4.86)	7.8 (7.20)	7.0 (5.37)
Swollen Joint Count 24	8.5 (5.13)	10.0 (5.85)	10.0 (6.19)
Swollen Joint Count 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 Joint Score Week 8	13.9 (9.94)	14.0 (9.94)	13.5 (10.69)
Tender Joint Count Week 16	11.1 (10.24)	12.5 (8.36)	11.8 (9.09)
Tender Joint Score Week 24	13.6 (9.79)	15.6 (11.94)	15.2 (11.62)
Tender Joint Score Week 36	8.3 (9.10)	10.9 (10.68)	9.6 (10.81)
Tender Joint Score Week 52 (EOS)	9.3 (9.34)	11.9 (15.18)	9.4 (11.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1997
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-1.28
	Confidence Interval	(2-Sided) 95%; -3.230 to 0.671
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.991
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9098
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -2.074 to 1.848
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.996
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2480
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; -0.817 to 3.150
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.008
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Tender Joint Count (TJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1931
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-1.96
	Confidence Interval	(2-Sided) 95%; -4.909 to 0.996
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.500
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	-0.77
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -3.722 to 2.184
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.500
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4352
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; -1.805 to 4.180
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.520
	Estimation Comments

19. Secondary Outcome

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])
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.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
Disease Activty iDay 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 Activtiy 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 Activtiy 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 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 (EOS) Physician's Disease Activity Assessment. 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)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2008
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-4.16
	Confidence Interval	(2-Sided) 95%; -10.541 to 2.226
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.242
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 (EOS) Physician's Disease Activity Assessment. 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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	-0.39
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -6.771 to 5.994
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.242
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 52 (EOS) Physician's Disease Activity Assessment. 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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2498
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	3.77
	Confidence Interval	(2-Sided) 95%; -2.665 to 10.204
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.268
	Estimation Comments

20. Secondary Outcome

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])
Description	Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS]). Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS]) where 0 = no pain and 100 = severe pain.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
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 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 (EOS) Participants Pain Assessment. 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7322
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-1.23
	Confidence Interval	(2-Sided) 95%; -8.0302 to 5.841
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.592
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 (EOS) Participants Pain Assessment. 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5418
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-2.21
	Confidence Interval	(2-Sided) 95%; -9.347 to 4.920
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.623
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 52 (EOS) Participants Pain Assessment. 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7869
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -8.136 to 6.169
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.633
	Estimation Comments

21. Secondary Outcome

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)
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 visual analogue scale [VAS]). Patients rate how their Rheumatoid Arthritis has affected them, where 0 = very well and 100 = very poor.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
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 (23.16)	51.1 (20.49)	52.3 (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 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 (EOS) Participants Disease Activity Assessment. 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)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7097
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-1.28
	Confidence Interval	(2-Sided) 95%; -8.062 to 5.496
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.443
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 (EOS) Participants Disease Activity Assessment. 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)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6683
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-1.48
	Confidence Interval	(2-Sided) 95%; -8.280 to 5.317
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.453
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 52 (EOS) Participants Disease Activity Assessment. 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)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9548
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -7.078 to 6.682
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.494
	Estimation Comments

22. Secondary Outcome

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])
Description	the Health Assessment Questionnaire-Disability Index (HAQ-DI) contains 20 questions split into 8 categories (dressing & grooming, arising, eating, walking, hygiene, reach, grip & activities). Scores were: 0 = Without ANY Difficulty; 1 = With SOME Difficulty; 2 = With MUCH Difficulty; 3 = UNABLE to Do. Total scores were calculated as the summed category scores divided by the number of categories. Total HAQ-DI scores are presented which range from 0 to 3. Higher scores represent a worse outcome. Scores of 0 to 1 represent mild to moderate difficulty, 1 to 2 moderate disability, and 2 to 3 severe to very severe disability.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
HAQ-DI Day 1	1.610 (0.5728)	1.605 (0.6567)	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 (0.6394)	1.152 (0.6668)
HAQ-DI Week 24	1.209 (0.6071)	1.335 (0.6381)	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 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 (EOS) HAQ-DI (0-3). 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0505
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.339 to 0.000
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.086
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 (EOS) HAQ-DI (0-3). 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1141
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.307 to 0.033
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.086
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 52 (EOS) HAQ-DI )0-3). 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7111
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.139 to 0.204
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.087
	Estimation Comments

23. Secondary Outcome

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
Description	C-reactive protein (CRP) level (Mg/L). CRP is a marker for inflammation. a normal reading is <3 Mg/L. Higher values indicate disease related inflammation and increased cardiovascular risk. CRP levels between 3 Mg/L and 10 Mg/L are mildly elevated. Levels between 10 Mg/L and 100 Mg/L are moderately elevated and CRP levels above 100 Mg/L are severely elevated.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
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 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 (EOS) CRP. 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8183
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -4.113 to 3.253
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.871
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 (EOS) CRP. 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4186
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95%; -2.164 to 5.191
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.868
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 52 (EOS) CRP. 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).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3035
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	1.94
	Confidence Interval	(2-Sided) 95%; -1.768 to 5.655
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.885
	Estimation Comments

24. Secondary Outcome

Title	Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52
Description	Disease Activity Score 28- Erythrocyte Sedimentation Rate (DAS28-ESR) consisted of tender joint counts (TJC), swollen joint counts (SJC) & erythrocyte sedimentation rate (ESR). The formula is: [0.56*SQRT(tender 28 joint count)+0.28*SQRT(swollen 28 joint count)+0.7*ln(ESR)]+0.014*patient global health assessment. Total DAS28-ESR scores are presented. Total scores range from 2 (minimum) to 10 (maximum). A lower score represents a better patient outcome. A DAS28-ESR of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
DAS28-ESR Day 1	6.537 (0.8440)	6.533 (.07810)	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 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9249
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.375 to 0.413
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.200
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Measn Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.351 to 0.442
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.201
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8962
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means Diference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.376 to 0.430
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.205
	Estimation Comments

25. Secondary Outcome

Title	Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks
Description	Efficacy endpoint: number of participants with a major clinical response defined as a continuous ACR70 from Baseline (Day 1) for at least 24 weeks. ACR70 is a measure based on American College of Rheumatology criteria of at least a 70% improvement in the number of tender and swollen joints, and a 70% improvement in at least 3 of the following: the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function measured using the Stanford Health Assessment Questionnaire the physician's global assessment of disease status; serum C-reactive protein levels.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
Major Clinical Response Week 24	1 1%	0 0%	0 0%
Major Clinical Response Week 52 (EOS)	2 2%	0 0%	1 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 (EOS) Major Clinical Response. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -2.56 to 7.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.57
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 (EOS) Major Clinical Response. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -4.74 to 6.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 52 (EOS) Major Clinical Response. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -6.75 to 3.39
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.24
	Estimation Comments

26. Secondary Outcome

Title	Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52
Description	Number if Participants with a Clinical Remission Response (CRR) defined by the Simplified Disease Activity Index (SDAI) <3.3 at weeks 8, 16, 24, 36 and 52 (EOS).
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
CRR Week 8	0 0%	0 0%	0 0%
CRR Week 16	0 0%	1 1%	0 0%
CRR Week 24	0 0%	1 1%	0 0%
CRR Week 36	2 2%	0 0%	1 1%
CRR Week 52 (EOS)	1 1%	2 2%	2 2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 (EOS). 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -6.9 to 3.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.92
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 (EOS). 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -7.07 to 3.86
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.95
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	Week 52 (EOS). 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Differnce (%)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -6.05 to 5.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.27
	Estimation Comments

27. Secondary Outcome

Title	Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52
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.
Time Frame	Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	98	98	98
Week 8 Good	12 12.2%	14 14.3%	12 12.2%
Week 8 Good or Moderate	30 30.6%	33 33.7%	33 33.7%
Week 16 Good	20 20.4%	12 12.2%	13 13.3%
Week 16 Good or Moderate	44 44.9%	42 42.9%	33 33.7%
Week 24 Good	12 12.2%	7 7.1%	7 7.1%
Week 24 Good or Moderate	30 30.6%	26 26.5%	23 23.5%
Week 36 Good	27 27.6%	15 15.3%	27 27.6%
Week 36 Good or Moderate	58 59.2%	50 51%	54 55.1%
Week 52 (EOS) Good	34 34.7%	31 31.6%	32 32.7%
Week 52 (EOS) Good or Moderate	59 60.2%	50 51%	63 64.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	Week 52 EULAR score 'Good'. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -12.59 to 15.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.19
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 EULAR score 'Good'. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -13.75 to 14.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.21
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	Week 52 EULAR score 'Good'. 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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -15.14 to 12.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.29
	Estimation Comments

28. Secondary Outcome

Title	Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels)
Description	Change from baseline (Day 1) in immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) levels (mg/dL) at Week 8, 16, 24 36 and 52 (End of study)
Time Frame	Baseline (Day 1) and Weeks 8, 16, 24, 36 and 52 (EOS)

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	95	96	93
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 36	1076.6 (246.62)	1060.9 (305.12)	976.6 (249.11)
IgG Week 52 (EOS)	1102.0 (274.44)	1081.1 (285.13)	999.9 (232.03)
IgM Screening	164.3 (76.07)	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	321.1 (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 (204.14)	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	269.4 (116.74)	254.7 (115.38)	297.8 (138.63)

29. Other Pre-specified Outcome

Title	Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24
Description	Pharmacodynamic endpoint: proportion of participants (n) with depletion of CD19+ B-cell count up to week 24 (Pharmacodynamic analysis set).
Time Frame	Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic data set

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	95	96	94
Number [participants]	45 45.9%	46 46.9%	50 51%

30. Other Pre-specified Outcome

Title	Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion
Description	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).
Time Frame	Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Analysis Set. Two participants in the SAIT101 arm, 3 participants in the MabThera arm and 3 participants in the Rituxan arm were excluded from the analysis either as they had a depleted C-cell count at baseline and / or if the Week 24 assessment was missing.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	93	90
Mean (Standard Deviation) [Days]	1.524 (2.6274)	2.847 (9.1286)	2.223 (9.0833)

31. Other Pre-specified Outcome

Title	Pharmacodynamic Endpoint: Duration of CD19+ B-cell Depletion
Description	Duration of CD19+ B-cell depletion (only participants that returned to non-depletion at or before week 24 were included)
Time Frame	Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Analysis Set.Pharmacodynamic Analysis Set. Fifty seven participants in the SAIT101 arm, 70 participants in the MabThera arm and 72 participants in the Rituxan arm were excluded from the analysis either as they had a depleted C-cell count at baseline or if the Week 24 assessment was missing.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	36	26	21
Mean (Standard Deviation) [Days]	78.444 (77.5290)	85.856 (73.4460)	77.290 (72.0557)

32. Other Pre-specified Outcome

Title	Pharmacodynamic Endpoint: Number of Participants With CD19+ B-cell Count Recover Versus Baseline
Description	Number of participants with CD19+ B-cell count recover versus baseline. Incidence of B-Cell recovery was defined as either CD19+ B-cell counts retuned to baseline or the lower limit or normal of 110 cells/µL at week 24).
Time Frame	Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Analysis Set

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	93	93	90
Count of Participants [Participants]	5 5.1%	4 4.1%	3 3.1%

33. Other Pre-specified Outcome

Title	Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24
Description	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
Time Frame	Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Analysis Set. AUC0-d15 could not be determined for 23 participants in the SAIT101 arm, 20 participants in the MabThera arm and 20 participants in the Rituxan arm as either the baseline data was missing and /or there was a missing b-cell could at the last timepoint.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	72	76	73
AUEC(0-d15)	-2650.0	-2672.1	-2719.4
AUEC(0-w24)	-32707.6	-33018.3	-33003.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.
	Type of Statistical Test	Other
	Comments	Statistical comparison of CD19+ B-cell pharmacokinetic parameters at Day 15 [AUEC(0-d15)]
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Statistical Comparisons Difference
	Estimated Value	22.1
	Confidence Interval	(2-Sided) 90%; -137.1 to 181.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.
	Type of Statistical Test	Other
	Comments	Statistical comparison of CD19+ B-cell pharmacokinetic parameters at Day 15 [AUEC(0-d15)]
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Statistical Comparisons Difference
	Estimated Value	69.5
	Confidence Interval	(2-Sided) 90%; -91.8 to 230.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.
	Type of Statistical Test	Other
	Comments	Statistical comparison of CD19+ B-cell pharmacokinetic parameters at Day 15 [AUEC(0-d15)]
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Statistical Comparisons Difference
	Estimated Value	47.4
	Confidence Interval	(2-Sided) 90%; -112.5 to 207.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	SAIT101, MabThera
	Comments	The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.
	Type of Statistical Test	Other
	Comments	Statistical comparison of CD19+ B-cell pharmacokinetic parameters at Day week [AUEC(0-w24)]
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Statistical Comparisons Difference
	Estimated Value	310.7
	Confidence Interval	(2-Sided) 90%; -187.9 to 809.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	SAIT101, Rituxan
	Comments	The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.
	Type of Statistical Test	Other
	Comments	Statistical comparison of CD19+ B-cell pharmacokinetic parameters at Day week [AUEC(0-w24)]
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Statistical Comparisons Difference
	Estimated Value	296.1
	Confidence Interval	(2-Sided) 90%; -213.8 to 806.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	MabThera, Rituxan
	Comments	The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.
	Type of Statistical Test	Other
	Comments	Statistical comparison of CD19+ B-cell pharmacokinetic parameters at Day week [AUEC(0-w24)]
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Statistical Comparisons Difference
	Estimated Value	-14.6
	Confidence Interval	(2-Sided) 90%; -527.4 to 498.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Other Pre-specified Outcome

Title	Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period
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])
Time Frame	Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Analysis Set. participants in the SAIT101 arm, Twenty three participants in the MabThera arm, 20 participants in the MabThera and 20 participants in the Rituxan arm were excluded from the analysis either as they had a depleted C-cell count at baseline and / or the Week 24 assessment was missing.

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	72	76	73
AUEC(0-d15)	-2729 (1915.3)	-2935 (2222.1)	-2367 (1978.1)
AUEC(0-w24)	-33500 (23881)	-36410 (22883)	-28500 (20878)

35. Other Pre-specified Outcome

Title	Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52
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)
Time Frame	Baseline (Day 1) and Weeks 8, 16, 24, 26 & 52 (EOS)

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Analysis Set

Arm/Group Title	SAIT101	MabThera	Rituxan
Arm/Group Description	1000 mg intravenous (iv) SAIT101 on Day 1 and 15 (Part A). 1000 mg iv SAIT101 on week 24 and 26 (Part B) for eligible participants,	1000 mg iv MabThera on Day 1 and 15 (Part A). 1000 mg iv MabThera on week 24 and 26 (Part B) for eligible participants.	1000 mg iv of Rituxan on Day 1 and 15 (Part A). 1000 mg iv of Rituxan on week 24 and 26 (Part B) for eligible participants
Measure Participants	95	96	93
CRP Day 1	19.5 (29.50)	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)

Adverse Events

Time Frame	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 (e.g. SAEs related to invasive procedures such s biopsies). All adverse events were collected for each patient from the start of the first infusion of study drug on Day 1 until the Week 52 Data-cut off.
Adverse Event Reporting Description	Safety Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
Arm/Group Title	SAIT101		MabThera		Rituxan
Arm/Group Description	SAIT101: 1,000 mg i.v. of SAIT101 on Day 1 and 15. 1,000 mg i.v. of SAIT101 on week 24 and 26 for eligible participants.		MabThera: 1,000 mg i.v. of MabThera® on Day 1 and 15. 1,000 mg i.v. of MabThera® on week 24 and 26 for eligible participants.		Rituxan: 1,000 mg i.v. of Rituxan® on Day 1 and 15. 1,000 mg i.v. of Rituxan® on week 24 and 26 for eligible participants.
All Cause Mortality
	SAIT101		MabThera		Rituxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/98 (0%)		0/98 (0%)		1/98 (1%)
Serious Adverse Events
	SAIT101		MabThera		Rituxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/98 (7.1%)		7/98 (7.1%)		13/98 (13.3%)
Blood and lymphatic system disorders
Anemia	0/98 (0%)	0	1/98 (1%)	1	0/98 (0%)	0
Febrile neutropenia	1/98 (1%)	1	0/98 (0%)	0	0/98 (0%)	0
Cardiac disorders
Cardiac failure	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	2
Immune system disorders
Anaphylactic reaction	1/98 (1%)	1	0/98 (0%)	0	0/98 (0%)	0
Drug hypersensitivity	1/98 (1%)	1	0/98 (0%)	0	0/98 (0%)	0
Infections and infestations
Herpes zoster	0/98 (0%)	0	2/98 (2%)	2	0/98 (0%)	0
Cellulitis	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Hepatitis B	1/98 (1%)	1	0/98 (0%)	0	0/98 (0%)	0
Hepatitis B reactivation	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Herpes simplex	1/98 (1%)	1	0/98 (0%)	0	0/98 (0%)	0
Lower respiratory tract infection	0/98 (0%)	0	1/98 (1%)	1	0/98 (0%)	0
Meningitis	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Meningitis bacterial	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Nasopharyngitis	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Pyelonephritis acute	1/98 (1%)	1	0/98 (0%)	0	0/98 (0%)	0
Urinary tract infection	1/98 (1%)	1	0/98 (0%)	0	0/98 (0%)	0
Urosepsis	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Injury, poisoning and procedural complications
Femoral neck fracture	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Femur fracture	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Foot fracture	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Humerus fracture	0/98 (0%)	0	1/98 (1%)	1	0/98 (0%)	0
Skin laceration	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Subdural hematoma	0/98 (0%)	0	1/98 (1%)	1	0/98 (0%)	0
Metabolism and nutrition disorders
Hypokalemia	1/98 (1%)	1	0/98 (0%)	0	0/98 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/98 (0%)	0	1/98 (1%)	1	0/98 (0%)	0
Oseoarthritis	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Nervous system disorders
Epilepsy	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Renal and urinary disorders
Acute kidney injury	0/98 (0%)	0	1/98 (1%)	1	0/98 (0%)	0
Renal cyst	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress	0/98 (0%)	0	0/98 (0%)	0	1/98 (1%)	1
Interstitial lung disease	0/98 (0%)	0	1/98 (1%)	1	0/98 (0%)	0
Other (Not Including Serious) Adverse Events
	SAIT101		MabThera		Rituxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/98 (39.8%)		37/98 (37.8%)		43/98 (43.9%)
Blood and lymphatic system disorders
Anemia	3/98 (3.1%)	3	8/98 (8.2%)	9	3/98 (3.1%)	3
Gastrointestinal disorders
Gastritis	3/98 (3.1%)	3	1/98 (1%)	1	5/98 (5.1%)	5
Infections and infestations
Urinary tract infection	13/98 (13.3%)	14	4/98 (4.1%)	6	8/98 (8.2%)	10
Upper respiratory tract infection	5/98 (5.1%)	5	8/98 (8.2%)	10	5/98 (5.1%)	5
Nasopharyngitis	7/98 (7.1%)	9	3/98 (3.1%)	4	7/98 (7.1%)	7
Injury, poisoning and procedural complications
Infusion related reaction	2/98 (2%)	2	2/98 (2%)	2	7/98 (7.1%)	8
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	4/98 (4.1%)	7	6/98 (6.1%)	6	6/98 (6.1%)	7
Vascular disorders
Hypertension	2/98 (2%)	2	5/98 (5.1%)	5	2/98 (2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.