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

• ClinicalTrials.gov Identifier: NCT02819726
• Recruitment Status: Completed
• First Posted: June 30, 2016
• Results First Posted: February 17, 2020
• Last Update Posted: February 17, 2020
• Sponsor: Archigen Biotech Limited
• Information provided by (Responsible Party): Archigen Biotech Limited

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis
• Interventions: Biological: SAIT101; Biological: MabThera; Biological: Rituxan
• Enrollment: 294

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.
Pre-assignment Details

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 [1]	98	98	98	0
Completed	92	88	87	0
Not Completed	6	10	11	0
Reason Not Completed
Lost to Follow-up	0	1	0	0
Withdrawal by Subject	3	5	6	0
Protocol non-compliance	3	4	5	0
[1] Received at least 1 infusion of study treatment in Part A
Period Title: Part B (All Participants)
Started [1]	73 [2]	70 [3]	39 [4]	38 [4]
Completed	70	68	35	36
Not Completed	3	2	4	2
Reason Not Completed
Lost to Follow-up	1	1	2	2
Withdrawal by Subject	2	1	1	0
Protocol non-compliance	0	0	1	0
[1] Received at least 1 infusion of treatment in Part B. 220 participants were re-treated in Part B; [2] 19 participants who completed Part A were not eligible for Part B; [3] 18 participants completing Part A were not eligible for Part B; [4] 5 participants completing Part A were ineligible for Part B.

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 Number of Baseline Participants		98	98	98	294
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		50.9 (12.41)	52.5 (10.87)	52.1 (12.09)	51.8 (11.79)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
18-60 years	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		76 77.6%	75 76.5%	71 72.4%	222 75.5%
>60 years	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		22 22.4%	23 23.5%	27 27.6%	72 24.5%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	98 participants	98 participants	98 participants	294 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); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	98 participants	98 participants	98 participants	294 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 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	98 participants	98 participants	98 participants	294 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 0.0%	0 0.0%
	Black or African American	2 2.0%	0 0.0%	1 1.0%	3 1.0%
	White	52 53.1%	56 57.1%	52 53.1%	160 54.4%
	More than one race	2 2.0%	3 3.1%	0 0.0%	5 1.7%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
South Korea	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		5	3	6	14
Hungary	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		3	0	4	7
Czechia	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		7	3	2	12
United States	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		9	13	6	28
Poland	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		15	19	23	57
Mexico	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		27	21	21	69
Bulgaria	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		4	5	4	13
Bosnia and Herzegovina	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		4	3	1	7
Germany	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		2	3	2	8
India	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		13	16	17	46
Spain	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		9	12	12	33
Disease duration; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		9.8 (6.73)	11.2 (7.72)	9.3 (7.10)	10.1 (7.22)
C-reactive protein [1]; Mean (Standard Deviation); Unit of measure: mg/L
	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		19.5 (28.99)	15.3 (20.63)	16.2 (17.91)	17.0 (2.99)
		[1] Measure 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.
Erythrocyte sedimentation rate [1]; Mean (Standard Deviation); Unit of measure: Mm/hr
	Number Analyzed	97 participants	97 participants	97 participants	291 participants
		51.0 (26.58)	47.5 (22.87)	51.5 (23.35)	50.0 (24.31)
		[1] Measure Analysis Population Description: Results were not available for 1 participant in each treatment arm
Swollen Joint Count (SJC66) [1]; Mean (Standard Deviation); Unit of measure: Joints
	Number Analyzed	98 participants	97 participants	98 participants	293 participants
		15.2 (7.97)	15.2 (7.01)	13.0 (6.19)	14.5 (7.14)
		[1] Measure Analysis Population Description: Results were not available for 1 participant in the MabThera treatment arm
Tender Joint Count (TJC68) [1]; Mean (Standard Deviation); Unit of measure: Joints
	Number Analyzed	98 participants	97 participants	98 participants	293 participants
		21.7 (11.08)	22.6 (13.66)	20.0 (10.84)	21.4 (11.93)
		[1] Measure Analysis Population Description: Results were not available for 1 participant in the MabThera treatment arm
Patient Global Assessments Visual Analogue Scale (VAS) Score [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	97 participants	97 participants	97 participants	291 participants
		68.9 (15.87)	67.6 (17.53)	70.8 (17.04)	69.1 (16.82)
		[1] Measure Description: Patients 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.; [2] Measure Analysis Population Description: Results were not available for 1 participant in each treatment arm
Physician Global Assessment VAS Score [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	97 participants	97 participants	98 participants	292 participants
		71.0 (14.3)	69.4 (15.9)	69.8 (14.32)	70.1 (14.51)
		[1] Measure Description: 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.; [2] Measure Analysis Population Description: Results were not available for 1 participant in the SAIT101 treatment arm and 1 participant in the MabThera treatment arm
Patient Pain Assessment VAS Score [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	98 participants	98 participants	97 participants	293 participants
		67.0 (18.71)	68.8 (20.02)	70.7 (19.06)	68.8 (19.27)
		[1] Measure Description: Patients assessment of pain (assessed on 1 to 100 mm Visual Analog Scale [VAS]) where 0 = no pain and 100 = severe pain.; [2] Measure Analysis Population Description: Results were not available for 1 participant in the Rituxan treatment arm
Health Assessment Questionnaire Disability Index (HAQ-DI) Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score
	Number Analyzed	98 participants	98 participants	97 participants	293 participants
		1.7 (0.57)	1.7 (0.64)	1.6 (0.64)	1.7 (0.62)
		[1] Measure Description: 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.; [2] Measure Analysis Population Description: Results were not available for 1 participant in the Rituxan treatment arm
Disease activity score based on a 28-joint count-C-Reactive Protein (DAS-28-CRP( [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	98 participants	97 participants	98 participants	293 participants
		5.28 (0.890)	5.29 (0.807)	5.17 (0833)	5.25 (0.843)
		[1] Measure Description: Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) consisted of tender joint counts (TJC), swollen joint counts (SJC) & C-reactive protein (CRP) blood levels. Total DAS28-CRPscores 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.; [2] Measure Analysis Population Description: Results were not available for 1 participant in the MabThera treatment arm
Disease activity score based on a 28-joint count - Erythrocyte sedimentation Rate (DAS28-ESR) [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	96 participants	96 participants	96 participants	288 participants
		6.54 (0.844)	6.53 (0.781)	6.48 (0.758)	6.52 (0.793)
		[1] Measure 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 represented 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. .; [2] Measure Analysis Population Description: Results were not available for 2 participants in each treatment arm
Anti-drug Antibody (ADA) Status Positive [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	98 participants	98 participants	96 participants	292 participants
		2 2.0%	1 1.0%	4 4.2%	7 2.4%
		[1] Measure Analysis Population Description: Results were not available for 2 participants in the Rituxan arm
Height [1]; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	98 participants	98 participants	97 participants	293 participants
		162.6 (9.29)	161.3 (8.79)	163.3 (8.37)	162.4 (8.83)
		[1] Measure Analysis Population Description: Results were not available for 1 participant in the Rituxan treatment arm
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	98 participants	98 participants	98 participants	294 participants
		73.0 (17.62)	71.9 (16.94)	71.6 (17.99)	72.2 (17.47)
Body Mass Index (BMI) [1]; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	98 participants	98 participants	97 participants	293 participants
		27.5 (5.48)	27.5 (5.46)	26.7 (5.95)	27.2 (5.63)
		[1] Measure Analysis Population Description: Results were not available for 1 participant in the Rituxan treatment arm

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
Overall Number of Participants Analyzed	79	70	76
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Method of Estimation	Estimation Parameter	GLS Mean Ration
	Estimated Value	95.33
	Confidence Interval	(2-Sided) 90%; 87.07 to 104.37
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	93.43
	Confidence Interval	(2-Sided) 90%; 85.54 to 102.15
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	98.06
	Confidence Interval	(2-Sided) 90%; 89.49 to 107.45
	Estimation Comments	[Not Specified]

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
Overall Number of Participants Analyzed	93	91	91
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	94.07
	Confidence Interval	(2-Sided) 90%; 86.91 to 101.81
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ration
	Estimated Value	94.39
	Confidence Interval	(2-Sided) 90%; 87.21 to 102.16
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	100.35
	Confidence Interval	(2-Sided) 90%; 92.68 to 108.65
	Estimation Comments	[Not Specified]

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
Overall Number of Participants Analyzed	91	88	83
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	96.31
	Confidence Interval	(2-Sided) 90%; 90.52 to 102.46
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	98.65
	Confidence Interval	(2-Sided) 90%; 92.64 to 105.05
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	102.43
	Confidence Interval	(2-Sided) 90%; 96.14 to 109.14
	Estimation Comments	[Not Specified]

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
Overall Number of Participants Analyzed	94	93	93
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	94.93
	Confidence Interval	(2-Sided) 90%; 89.03 to 101.23
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	98.75
	Confidence Interval	(2-Sided) 90%; 92.61 to 105.30
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	104.03
	Confidence Interval	(2-Sided) 90%; 97.54 to 110.95
	Estimation Comments	[Not Specified]

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
Overall Number of Participants Analyzed	83	81	77
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	89.08
	Confidence Interval	(2-Sided) 90%; 77.20 to 102.79
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	102.56
	Confidence Interval	(2-Sided) 90%; 88.72 to 118.56
	Estimation Comments	[Not Specified]

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
Method of Estimation	Estimation Parameter	GLS Mean Ratio
	Estimated Value	115.13
	Confidence Interval	(2-Sided) 90%; 99.51 to 133.21
	Estimation Comments	[Not Specified]

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
Overall Number of Participants Analyzed	91	87	85
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed	64	61	65
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Overall Number of Participants Analyzed	93	89	92
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Overall Number of Participants Analyzed	93	92	91
Median (Inter-Quartile Range); Unit of Measure: Hours
	5.167; (3.00 to 6.50)	5.167; (3.00 to 358.75)	4.500; (3.00 to 6.75)

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
Overall Number of Participants Analyzed	94	93	93
Median (Inter-Quartile Range); Unit of Measure: Hours
	4.167; (2.92 to 5.50)	4.167; (0.00 to 48.08)	4.250; (2.92 to 23.50)

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
Overall Number of Participants Analyzed	93	91	92
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	93	91	91
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Overall Number of Participants Analyzed	93	91	91
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Overall Number of Participants Analyzed	93	91	92
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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
Overall Number of Participants Analyzed		98	97	98
Mean (Standard Deviation); Unit of Measure: score on a scale
Day 1 (Baseline)	Number Analyzed	98 participants	97 participants	98 participants
		5.282 (0.8899)	5.288 (0.8073)	5.170 (0.8326)
Week 8	Number Analyzed	93 participants	93 participants	93 participants
		4.405 (1.0189)	4.324 (1.1132)	4.251 (1.1392)
Week 16	Number Analyzed	93 participants	93 participants	92 participants
		4.001 (1.1116)	4.155 (0.9750)	4.100 (1.0044)
Week 24	Number Analyzed	91 participants	88 participants	85 participants
		4.300 (1.0331)	4.463 (1.0648)	4.443 (0.9774)
Week 36	Number Analyzed	90 participants	83 participants	84 participants
		3.552 (1.1452)	3.823 (0.9290)	3.716 (1.0684)
Week 52 (End of Study(	Number Analyzed	92 participants	88 participants	87 participants
		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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6068
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5990
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3053
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants
ACR20 Week 8	Number Analyzed	95 participants	93 participants	92 participants
		39; (31.70 to 51.10)	33; (26.51 to 45.61)	44; (37.91 to 57.91)
ACR20 Week 16	Number Analyzed	94 participants	92 participants	91 participants
		50; (43.18 to 62.95)	54; (48.48 to 68.21)	53; (47.98 to 67.84)
ACR20 Week 24	Number Analyzed	92 participants	87 participants	86 participants
		36; (28.79 to 49.35)	31; (26.37 to 46.11)	34; (29.86 to 50.10)
ACR20 Week 36	Number Analyzed	90 participants	82 participants	83 participants
		63; (59.87 to 78.49)	47; (46.52 to 67.46)	58; (58.00 to 78.69)
ACR20 Week 52 (EOS)	Number Analyzed	94 participants	90 participants	89 participants
		60; (53.75 to 72.82)	49; (44.18 to 64.34)	59; (55.98 to 75.26)

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants
ACR50 Week 8	Number Analyzed	95 participants	93 participants	93 participants
		13; (8.17 to 22.02)	11; (6.73 to 19.95)	14; (9.29 to 23.94)
ACR70 Week 8	Number Analyzed	95 participants	93 participants	92 participants
		2; (0.58 to 7.35)	2; (0.59 to 7.51)	2; (0.60 to 7.58)
ACR50 Week 16	Number Analyzed	94 participants	92 participants	91 participants
		17; (11.61 to 27.07)	16; (11.00 to 26.40)	14; (9.39 to 24.18)
ACR70 Week 16	Number Analyzed	94 participants	92 participants	91 participants
		9; (5.12 to 17.20)	4; (1.70 to 10.65)	5; (2.37 to 12.22)
ACR50 Week 24	Number Analyzed	92 participants	87 participants	86 participants
		15; (10.14 to 25.17)	8; (4.73 to 17.11)	5; (2.51 to 12.90)
ACR70 Week 24	Number Analyzed	92 participants	87 participants	86 participants
		8; (4.47 to 16.23)	2; (0.63 to 8.00)	3; (1.19 to 9.76)
ACR50 Week 36	Number Analyzed	90 participants	82 participants	83 participants
		37; (31.51 to 51.44)	19; (15.37 to 33.38)	25; (21.31 to 40.69)
ACR70 Week 36	Number Analyzed	90 participants	82 participants	83 participants
		19; (13.95 to 30.63)	6; (3.40 to 15.06)	12; (8.47 to 23.59)
ACR50 Week 52 (EOS)	Number Analyzed	94 participants	90 participants	89 participants
		35; (28.14 to 47.33)	25; (19.58 to 37.80)	30; (24.74 to 44.02)
ACR70 Week 52 (EOS)	Number Analyzed	94 participants	90 participants	89 participants
		23; (16.89 to 34.05)	13; (8.64 to 23.16)	17; (12.28 to 28.48)

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Least Squares Mean (Standard Deviation); Unit of Measure: Joints
Swollen Joint Count Day 1	Number Analyzed	98 participants	97 participants	98 participants
		15.2 (7.97)	15.2 (15.2)	13.0 (6.19)
Swollen Joint Count Week 8	Number Analyzed	95 participants	94 participants	93 participants
		8.6 (7.11)	8.4 (6.62)	7.7 (5.92)
Swollen Joint Count 16	Number Analyzed	94 participants	93 participants	92 participants
		6.5 (4.86)	7.8 (7.20)	7.0 (5.37)
Swollen Joint Count 24	Number Analyzed	92 participants	88 participants	87 participants
		8.5 (5.13)	10.0 (5.85)	10.0 (6.19)
Swollen Joint Count 36	Number Analyzed	90 participants	83 participants	85 participants
		4.8 (6.21)	5.4 (5.72)	5.7 (5.49)
Swollen Joint Count Week 52 (EOS)	Number Analyzed	94 participants	91 participants	90 participants
		5.2 (6.53)	6.5 (9.46)	4.6 (5.04)
Tender Joint Count Day 1	Number Analyzed	98 participants	97 participants	98 participants
		21.7 (11.08)	22.6 (13.66)	20.0 (10.84)
Tender Joint Score Week 8	Number Analyzed	95 participants	94 participants	93 participants
		13.9 (9.94)	14.0 (9.94)	13.5 (10.69)
Tender Joint Count Week 16	Number Analyzed	94 participants	93 participants	92 participants
		11.1 (10.24)	12.5 (8.36)	11.8 (9.09)
Tender Joint Score Week 24	Number Analyzed	92 participants	88 participants	87 participants
		13.6 (9.79)	15.6 (11.94)	15.2 (11.62)
Tender Joint Score Week 36	Number Analyzed	90 participants	83 participants	85 participants
		8.3 (9.10)	10.9 (10.68)	9.6 (10.81)
Tender Joint Score Week 52 (EOS)	Number Analyzed	94 participants	91 participants	90 participants
		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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1997
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9098
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2480
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1931
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	-0.77
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4352
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
Disease Activty iDay 1	Number Analyzed	97 participants	97 participants	98 participants
		71.0 (14.30)	69.4 (15.00)	69.8 (14.32)
Disease Activity Week 8	Number Analyzed	95 participants	93 participants	91 participants
		45.6 (20.75)	43.2 (23.86)	44.6 (23.28)
Disease Activtiy Week 16	Number Analyzed	93 participants	93 participants	91 participants
		39.2 (20.94)	39.0 (20.97)	42.3 (20.89)
Disease Activity Week 24	Number Analyzed	91 participants	87 participants	87 participants
		47.9 (22.28)	47.8 (20.25)	49.0 (22.45)
Disease Activtiy Week 36	Number Analyzed	90 participants	83 participants	86 participants
		30.3 (21.56)	36.3 (21.71)	31.4 (20.69)
Disease Activity Week 52 (EOS)	Number Analyzed	94 participants	91 participants	90 participants
		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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2008
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	-0.39
	Comments	[Not Specified]
	Method	ANOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2498
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Least Squares Mean (Standard Deviation); Unit of Measure: score on a scale
Assessment of Pain Day 1	Number Analyzed	98 participants	98 participants	97 participants
		67.0 (18.71)	68.8 (20.02)	68.8 (19.27)
Assessment of Pain Week 8	Number Analyzed	95 participants	93 participants	92 participants
		48.4 (22.79)	50.4 (22.40)	47.9 (23.03)
Assessment of Pain Week 16	Number Analyzed	94 participants	91 participants	92 participants
		42.7 (23.34)	44.6 (20.91)	44.4 (22.91)
Assessment of Pain Week 24	Number Analyzed	92 participants	88 participants	86 participants
		49.3 (24.15)	51.6 (21.44)	51.8 (23.58)
Assessment of Pain Week 36	Number Analyzed	90 participants	83 participants	84 participants
		36.8 (24.56)	44.9 (23.78)	41.6 (23.46)
Assessment of Pain Week 52 (EOS)	Number Analyzed	94 participants	91 participants	91 participants
		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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7322
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5418
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7869
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Least Squares Mean (Standard Deviation); Unit of Measure: score on a scale
Disease activity Day 1	Number Analyzed	97 participants	97 participants	97 participants
		68.9 (15.87)	67.6 (17.53)	70.8 (17.04)
Disease activity Week 8	Number Analyzed	95 participants	94 participants	93 participants
		46.9 (22.57)	49.1 (22.98)	48.5 (22.93)
Disease activity Week 16	Number Analyzed	94 participants	93 participants	92 participants
		43.9 (21.47)	44.4 (21.63)	44.2 (22.82)
Disease activity Week 24	Number Analyzed	92 participants	88 participants	86 participants
		50.8 (23.16)	51.1 (20.49)	52.3 (21.90)
Disease activity Week 36	Number Analyzed	90 participants	82 participants	85 participants
		35.7 (22.63)	42.7 (22.54)	42.5 (23.70)
Disease activity Week 52 (EOS)	Number Analyzed	95 participants	91 participants	91 participants
		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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7097
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6683
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9548
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Least Squares Mean (Standard Deviation); Unit of Measure: score on a scale
HAQ-DI Day 1	Number Analyzed	98 participants	98 participants	97 participants
		1.610 (0.5728)	1.605 (0.6567)	1.585 (0.6421)
HAQ-DI Week 8	Number Analyzed	95 participants	94 participants	93 participants
		1.168 (0.6318)	1.314 (0.6919)	1.176 (0.6398)
HAQ-DI Week 16	Number Analyzed	94 participants	93 participants	92 participants
		1.129 (0.5775)	1.246 (0.6394)	1.152 (0.6668)
HAQ-DI Week 24	Number Analyzed	92 participants	88 participants	86 participants
		1.209 (0.6071)	1.335 (0.6381)	1.294 (0.6594)
HAQ-DI Week 36	Number Analyzed	90 participants	83 participants	84 participants
		0.994 (0.6220)	1.182 (0.6883)	1.061 (0.6247)
HAQ-DI Week 52 (EOS)	Number Analyzed	94 participants	91 participants	91 participants
		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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0505
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1141
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7111
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Least Squares Mean (Standard Deviation); Unit of Measure: Mg/L
CRP Day 1	Number Analyzed	98 participants	98 participants	98 participants
		19.5 (28.99)	15.3 (20.63)	16.2 (17.91)
CRP Week 8	Number Analyzed	93 participants	93 participants	93 participants
		12.5 (15.78)	12.3 (20.29)	10.4 (12.78)
CRP Week 16	Number Analyzed	93 participants	93 participants	92 participants
		8.5 (11.78)	7.2 (9.02)	7.3 (6.90)
CRP Week 24	Number Analyzed	91 participants	88 participants	85 participants
		9.5 (14.54)	8.3 (14.40)	7.9 (10.35)
CRP Week 36	Number Analyzed	90 participants	83 participants	85 participants
		8.0 (20.33)	7.0 (10.38)	7.1 (9.72)
CRP Week 52 (EOS)	Number Analyzed	92 participants	88 participants	88 participants
		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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8183
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4186
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3035
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Mean (Standard Deviation); Unit of Measure: score on a scale
DAS28-ESR Day 1	Number Analyzed	96 participants	96 participants	96 participants
		6.537 (0.8440)	6.533 (.07810)	6.480 (0.7577)
DAS28-ESR Week 8	Number Analyzed	94 participants	92 participants	93 participants
		5.330 (1.0649)	5.315 (1.2478)	5.235 (1.2578)
DAS28-ESR Week 16	Number Analyzed	94 participants	92 participants	92 participants
		4.861 (1.1876)	5.059 (1.1682)	4.957 (1.1802)
DAS28-ESR Week 24	Number Analyzed	92 participants	87 participants	85 participants
		5.216 (1.2510)	5.410 (1.2344)	5.432 (1.1891)
DAS28-ESR Week 36	Number Analyzed	90 participants	80 participants	80 participants
		4.319 (1.2798)	4.689 (1.0077)	4.499 (1.1980)
DAS28-ESR Week 52 (EOS)	Number Analyzed	92 participants	86 participants	82 participants
		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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9249
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.05
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8962
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants
Major Clinical Response Week 24	Number Analyzed	92 participants	86 participants	85 participants
		1; (0.19 to 5.90)	0; (0.00 to 4.28)	0; (0.00 to 4.32)
Major Clinical Response Week 52 (EOS)	Number Analyzed	89 participants	81 participants	80 participants
		2; (0.62 to 7.83)	0; (0.00 to 4.53)	1; (0.22 to 6.75)

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants
CRR Week 8	Number Analyzed	93 participants	92 participants	91 participants
		0; (0.00 to 3.97)	0; (0.00 to 4.01)	0; (0.00 to 4.05)
CRR Week 16	Number Analyzed	92 participants	93 participants	91 participants
		0; (0.00 to 4.01)	1; (0.19 to 5.84)	0; (0.00 to 4.05)
CRR Week 24	Number Analyzed	90 participants	87 participants	84 participants
		0; (0.00 to 4.09)	1; (0.20 to 6.23)	0; (0.00 to 4.37)
CRR Week 36	Number Analyzed	90 participants	82 participants	83 participants
		2; (0.61 to 7.74)	0; (0.00 to 4.48)	1; (0.21 to 6.51)
CRR Week 52 (EOS)	Number Analyzed	92 participants	88 participants	86 participants
		1; (0.19 to 5.90)	2; (0.63 to 7.91)	2; (0.64 to 8.09)

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		98	98	98
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants
Week 8 Good	Number Analyzed	93 participants	92 participants	93 participants
		12; (7.54 to 21.21)	14; (9.29 to 23.94)	12; (7.54 to 21.21)
Week 8 Good or Moderate	Number Analyzed	93 participants	92 participants	93 participants
		30; (23.62 to 42.30)	33; (26.82 to 46.05)	33; (26.51 to 45.61)
Week 16 Good	Number Analyzed	93 participants	92 participants	92 participants
		20; (14.38 to 30.90)	12; (7.62 to 21.43)	13; (8.45 to 22.69)
Week 16 Good or Moderate	Number Analyzed	93 participants	92 participants	92 participants
		44; (37.47 to 57.36)	42; (35.85 to 55.80)	33; (26.82 to 46.05)
Week 24 Good	Number Analyzed	91 participants	87 participants	85 participants
		12; (7.71 to 21.65)	7; (3.95 to 15.69)	7; (4.05 to 16.04)
Week 24 Good or Moderate	Number Analyzed	91 participants	87 participants	85 participants
		30; (24.17 to 43.14)	26; (21.28 to 40.19)	23; (18.76 to 37.34)
Week 36 Good	Number Analyzed	90 participants	82 participants	84 participants
		27; (21.51 to 40.13)	15; (11.41 to 28.01)	27; (23.13 to 42.72)
Week 36 Good or Moderate	Number Analyzed	90 participants	82 participants	84 participants
		58; (54.15 to 73.56)	50; (50.00 to 70.82)	54; (53.62 to 73.70)
Week 52 (EOS) Good	Number Analyzed	92 participants	87 participants	87 participants
		34; (27.80 to 47.16)	31; (26.37 to 46.11)	32; (27.41 to 47.27)
Week 52 (EOS) Good or Moderate	Number Analyzed	92 participants	50 participants	87 participants
		59; (53.95 to 73.18)	50; (46.98 to 67.33)	63; (62.23 to 80.71)

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	[Not Specified]
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	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Difference (%)
	Comments	[Not Specified]
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	[Not Specified]

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	[Not Specified]
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	[Not Specified]

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
Overall Number of Participants Analyzed		95	96	93
Mean (Standard Deviation); Unit of Measure: Mg/dL
IgG Screening	Number Analyzed	95 participants	96 participants	93 participants
		1231.0 (299.36)	1230.1 (365.54)	1203.4 (373.29)
IgG Week 8	Number Analyzed	94 participants	94 participants	91 participants
		1108.0 (242.20)	1080.6 (279.75)	1038.5 (290.01)
IgG Week 16	Number Analyzed	91 participants	93 participants	91 participants
		1105.2 (232.51)	1075.7 (277.51)	1038.5 (290.01)
IgG Week 24	Number Analyzed	91 participants	83 participants	86 participants
		1114.6 (251.78)	1077.2 (265.55)	1023.2 (278.70)
IgG Week 36	Number Analyzed	89 participants	86 participants	84 participants
		1076.6 (246.62)	1060.9 (305.12)	976.6 (249.11)
IgG Week 52 (EOS)	Number Analyzed	89 participants	86 participants	87 participants
		1102.0 (274.44)	1081.1 (285.13)	999.9 (232.03)
IgM Screening	Number Analyzed	95 participants	96 participants	93 participants
		164.3 (76.07)	167.9 (100.16)	159.0 (81.36)
IgM Week 8	Number Analyzed	94 participants	94 participants	91 participants
		137.5 (71.38)	132.6 (83.58)	128.9 (68.50)
IgM Week 16	Number Analyzed	91 participants	94 participants	91 participants
		123.7 (61.08)	124.9 (85.71)	117.0 (60.44)
IgM Week 24	Number Analyzed	91 participants	86 participants	86 participants
		123.3 (62.37)	117.1 (80.96)	109.9 (73.11)
IgM Week 36	Number Analyzed	89 participants	83 participants	84 participants
		111.7 (56.89)	108.0 (77.79)	99.7 (56.38)
IgM Week 52 (EOS)	Number Analyzed	89 participants	86 participants	87 participants
		109.6 (56.80)	107.6 (77.00)	95.2 (52.57)
IgA Screening	Number Analyzed	95 participants	96 participants	93 participants
		321.1 (269.22)	283.4 (134.80)	342.9 (153.24)
IgA Week 8	Number Analyzed	93 participants	94 participants	93 participants
		293.6 (176.04)	264.4 (121.41)	316.5 (146.15)
IgA Week 16	Number Analyzed	91 participants	93 participants	91 participants
		301.8 (204.14)	253.0 (111.58)	312.7 (151.87)
IgA Week 24	Number Analyzed	91 participants	86 participants	91 participants
		279.8 (119.87)	263.0 (121.15)	307.7 (147.92)
IgA Week 36	Number Analyzed	89 participants	83 participants	89 participants
		283.8 (204.12)	259.2 (116.55)	297.1 (146.85)
IgA Week 52	Number Analyzed	89 participants	83 participants	89 participants
		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
Overall Number of Participants Analyzed	95	96	94
Measure Type: Number; Unit of Measure: participants
	45	46	50

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
Overall Number of Participants Analyzed	93	93	90
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	36	26	21
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	93	93	90
Measure Type: Count of Participants; Unit of Measure: Participants
	5 5.4%	4 4.3%	3 3.3%

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
Overall Number of Participants Analyzed		72	76	73
Least Squares Mean (95% Confidence Interval); Unit of Measure: cells*day/µL)
AUEC(0-d15)	Number Analyzed	72 participants	76 participants	73 participants
		-2650.0; (-2786.0 to -2513.9)	-2672.1; (-2804.9 to -2539.3)	-2719.4; (-2855.3 to 2583.6)
AUEC(0-w24)	Number Analyzed	56 participants	56 participants	52 participants
		-32707.6; (-33128.1 to -32287.1)