TL011 in Severe, Active Rheumatoid Arthritis Patients

• Sponsor: Teva Pharmaceutical Industries, Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01123070
• Collaborator: (none)
• Enrollment: 54
• Locations: 18
• Arms: 2
• Actual Duration (Months): 26.5
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and pharmacology of TL011 in patients with severe rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: TL011, anti CD20, for the treatment of rheumatoid arthritis; Biological: MabThera infusions	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase Ib Study Evaluating Safety, Pharmacokinetic and Pharmacodynamic Profiles of a Single Course of TL011 Infusions in Subjects With Severe, Active Rheumatoid Arthritis
• Actual Study Start Date: Feb 5, 2010
• Actual Primary Completion Date: Apr 23, 2012
• Actual Study Completion Date: Apr 23, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TL011 TL011 infusions	Biological: TL011, anti CD20, for the treatment of rheumatoid arthritis; TL011 administered by 2 infusions, 2 weeks apart
Active Comparator: MabThera MabThera infusions	Biological: MabThera infusions; MabThera, administered by 2 infusions, 2 weeks apart

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration Versus Time Curve [AUC(0-t)] in Part B [Day 1 to Day 57]

Secondary Outcome Measures

1. Maximum Observed Concentration (Cmax) in Part B [Day 1 to Day 57]

2. Number of Participants With Adverse Events in Part B [From randomization up to Week 24]

   An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

3. Cmax Post First Dose (C1max) and Post Second Dose (C2max) in Part B [Day 1, Day 15]

4. AUC At First Dose (AUC1) and AUC At Second Dose (AUC2) in Part B [Day 1, Day 15]

5. Percent Change From Baseline in CD19+ B-cell Count in Part B [Baseline to Day 57]

6. Number of Participants With American College of Rheumatology (ACR20) Criteria Response in Part B [Baseline to Day 57]

   Defined as at least 20% improvement from the screening values in swollen and tender joint count and in 3 of the following 5 disease activity measures. Physician's global assessment of disease activity (VAS) Patient's assessment of RA pain (VAS) Patient's global assessment of disease activity Patient's assessment of physical function (Health Assessment Questionnaire) Acute phase reactant (C-reactive protein [CRP])

7. Area Under the Plasma Concentration Versus Time Curve [AUC (0-t)] for Part A Cohort 2 [Day 1 to Day 57]

   Data available for cohort 2 only per planned analysis.

8. Number of Participants With Adverse Events in Part A [From randomization up to Week 24]

   An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adult subjects

• Rheumatoid arthritis as defined by the 1987 ACR Classification

• Severe active seropositive disease

• Inadequate response or intolerance to other DMARDs

• Treatment with MTX

Exclusion Criteria:

• Rheumatic autoimmune disease other than RA

• Active infection

• Known immunodeficiency syndrome

• Positive Hepatitis B surface antigen or antibodies to Hepatitis C

• History of cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 5428	Plzen		Czechia	323 00
2	Teva Investigational Site 5426	Prague 2		Czechia	12850
3	Teva Investigational Site 5429	Uherske Hradiste		Czechia	686 01
4	Teva Investigational Site 5123	Budapest		Hungary	1083
5	Teva Investigational Site 5122	Budapest		Hungary	H-1023
6	Teva Investigational Site 5125	Debrecen		Hungary	4032
7	Teva Investigational Site 5124	Szeged		Hungary	H-6720
8	Teva Investigational Site 3077	Firenze		Italy	50139
9	Teva Investigational Site 3075	Genova		Italy	16132
10	Teva Investigational Site 3078	Pavia		Italy	27100
11	Teva Investigational Site 3076	Siena		Italy	53100
12	Teva Investigational Site 3170	Barakaldo		Spain	48903
13	Teva Investigational Site 3168	Guadalajara		Spain	19002
14	Teva Investigational Site 3167	Madrid		Spain	28009
15	Teva Investigational Site 3169	Sevilla		Spain	41014
16	Teva Investigational Site 3434	Manchester		United Kingdom	M13 9WL
17	Teva Investigational Site 3433	Staffordshire		United Kingdom	WS11 5XY
18	Teva Investigational Site 3435	Wirral, Merseyside		United Kingdom	CH49 5PE

Sponsors and Collaborators

• Teva Pharmaceutical Industries, Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Pharmaceutical Industries, Ltd.
• ClinicalTrials.gov Identifier: NCT01123070
• Other Study ID Numbers: RA-TL011-101; 2009-015702-18
• First Posted: May 14, 2010
• Last Update Posted: Oct 4, 2021
• Last Verified: Sep 1, 2021

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Rituximab

Study Results

Participant Flow

Pre-assignment Detail	Part A was an open label dose escalation for TL011 with two cohorts. Part B was randomized, double blind with two treatment groups to compare TL011 to MabThera. There was an 8 weeks core study period followed by 16 weeks extended follow up period.

Arm/Group Title	Cohort 1 TL011 500 mg	Cohort 2 TL011 1000 mg	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Period Title: Part A Cohort 1 Open Label Period
STARTED	3	0	0	0
COMPLETED	3	0	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part A Cohort 1 Open Label Period
STARTED	0	3	0	0
COMPLETED	0	3	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part A Cohort 1 Open Label Period
STARTED	0	0	25	23
COMPLETED	0	0	21	20
NOT COMPLETED	0	0	4	3

Baseline Characteristics

Arm/Group Title	Cohort 1 TL011 500 mg	Cohort 2 TL011 1000 mg	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg	Total
Arm/Group Description	Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Total of all reporting groups
Overall Participants	3	3	25	23	54
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.56 (13.4)	55.2 (8.3)	56.8 (11.4)	56.7 (12.2)	56.7 (11.7)
Sex: Female, Male (Count of Participants)
Female	3 100%	2 66.7%	22 88%	18 78.3%	45 83.3%
Male	0 0%	1 33.3%	3 12%	5 21.7%	9 16.7%
Race/Ethnicity, Customized (Number) [Number]
Race : White	3 100%	3 100%	24 96%	23 100%	53 98.1%
Race : Other	0 0%	0 0%	1 4%	0 0%	1 1.9%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve [AUC(0-t)] in Part B
Time Frame	Day 1 to Day 57

Outcome Measure Data

Analysis Population Description

Pharmacokinetics (PK) population included all participants that received at least one dose of 1000 mg TL011 or MabThera and had sufficient plasma concentration results to allow estimation of PK parameters

Arm/Group Title	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	21	18
Geometric Mean (Standard Deviation) [Day*micrograms per milliliter]	7571 (2219)	8377 (2879)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double Blind TL011 1000 mg, Double Blind MabThera 1000 mg
	Comments
	Type of Statistical Test	Equivalence
	Comments	Bioequivalence declared if the back transformed 90% CI of geometric mean ratio is within the predefined limits of 0.75 to 1.33
Statistical Test of Hypothesis	p-Value	0.4265
	Comments
	Method	ANCOVA
	Comments	PK parameters were calculated using a logarithmic transformation. Covariates included body weight at screening, gender and treatment.
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.930
	Confidence Interval	(2-Sided) 90%; 0.797 to 1.084
	Parameter Dispersion	Type: Value:
	Estimation Comments	TL011 arm is the numerator and MabThera arm is the denominator

2. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) in Part B
Time Frame	Day 1 to Day 57

Outcome Measure Data

Analysis Population Description

Pharmacokinetics (PK) population included all participants that received at least one dose of 1000 mg TL011 or MabThera and had sufficient plasma concentration results to allow estimation of PK parameters

Arm/Group Title	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	21	19
Geometric Mean (Standard Deviation) [Micrograms per milliliter]	396 (84.2)	450 (109)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double Blind TL011 1000 mg, Double Blind MabThera 1000 mg
	Comments
	Type of Statistical Test	Equivalence
	Comments	Bioequivalence declared if the back transformed 90% CI of geometric mean ratio is within the predefined limits of 0.75 to 1.33
Statistical Test of Hypothesis	p-Value	0.0368
	Comments
	Method	ANCOVA
	Comments	PK parameters were calculated using a logarithmic transformation. Covariates included body weight at screening, gender and treatment.
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.862
	Confidence Interval	(2-Sided) 90%; 0.768 to 0.968
	Parameter Dispersion	Type: Value:
	Estimation Comments	TL011 arm is the numerator, MabThera arm is the denominator

3. Secondary Outcome

Title	Number of Participants With Adverse Events in Part B
Description	An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	From randomization up to Week 24

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least one dose of study drug.

Arm/Group Title	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	25	23
Count of Participants [Participants]	14 466.7%	16 533.3%

4. Secondary Outcome

Title	Cmax Post First Dose (C1max) and Post Second Dose (C2max) in Part B
Time Frame	Day 1, Day 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetics (PK) population included all participants that received at least one dose of 1000 mg TL011 or MabThera and had sufficient plasma concentration results to allow estimation of PK parameters. Here, "number analyzed" signifies participants evaluable for this outcome measure. Numbers analyzed were not equal at each time point (C1max and C2max).

Arm/Group Title	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	22	22
C1max	339 (68.2)	356 (74.7)
C2max	348 (124)	448 (110)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double Blind TL011 1000 mg, Double Blind MabThera 1000 mg
	Comments	Cmax1
	Type of Statistical Test	Equivalence
	Comments	Bioequivalence declared if the 90% CI of geometric mean ratio is within the predefined limits of 0.75 to 1.33
Statistical Test of Hypothesis	p-Value	0.1484
	Comments
	Method	ANCOVA
	Comments	PK parameters were calculated using a logarithmic transformation. Covariates included body weight at screening, gender and treatment.
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.909
	Confidence Interval	(2-Sided) 90%; 0.814 to 1.014
	Parameter Dispersion	Type: Value:
	Estimation Comments	TL011/MabThera

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double Blind TL011 1000 mg, Double Blind MabThera 1000 mg
	Comments	Cmax2
	Type of Statistical Test	Equivalence
	Comments	Bioequivalence declared if the 90% CI of geometric mean ratio is within the predefined limits of 0.75 to 1.33
Statistical Test of Hypothesis	p-Value	0.0241
	Comments
	Method	ANCOVA
	Comments	PK parameters were calculated using a logarithmic transformation. Covariates included body weight at screening, gender and treatment.
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.766
	Confidence Interval	(2-Sided) 90%; 0.633 to 0.927
	Parameter Dispersion	Type: Value:
	Estimation Comments	TL011/MabThera

5. Secondary Outcome

Title	AUC At First Dose (AUC1) and AUC At Second Dose (AUC2) in Part B
Time Frame	Day 1, Day 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetics (PK) population included all participants that received at least one dose of 1000 mg TL011 or MabThera and had sufficient plasma concentration results to allow estimation of PK parameters. Here, "number analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	22	22
AUC1	2335 (527)	2359 (634)
AUC2	6133 (2774)	6849 (4532)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double Blind TL011 1000 mg, Double Blind MabThera 1000 mg
	Comments	AUC1
	Type of Statistical Test	Equivalence
	Comments	Bioequivalence declared if the 90% CI of geometric mean ratio is within the predefined limits of 0.75 to 1.33
Statistical Test of Hypothesis	p-Value	0.6520
	Comments
	Method	ANCOVA
	Comments	PK parameters were calculated using a logarithmic transformation. Covariates included body weight at screening, gender and treatment.
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.969
	Confidence Interval	(2-Sided) 90%; 0.863 to 1.088
	Parameter Dispersion	Type: Value:
	Estimation Comments	TL011 arm is the numerator, MabThera arm is the denominator

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double Blind TL011 1000 mg, Double Blind MabThera 1000 mg
	Comments	AUC2
	Type of Statistical Test	Equivalence
	Comments	Bioequivalence declared if the 90% CI of geometric mean ratio is within the predefined limits of 0.75 to 1.33
Statistical Test of Hypothesis	p-Value	0.7835
	Comments
	Method	ANCOVA
	Comments	PK parameters were calculated using a logarithmic transformation. Covariates included body weight at screening, gender and treatment.
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.961
	Confidence Interval	(2-Sided) 90%; 0.757 to 1.222
	Parameter Dispersion	Type: Value:
	Estimation Comments	TL011/MabThera

6. Secondary Outcome

Title	Percent Change From Baseline in CD19+ B-cell Count in Part B
Time Frame	Baseline to Day 57

Outcome Measure Data

Analysis Population Description

PK population. Here, "number analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	20	18
Mean (Standard Deviation) [Percent change]	-88.9 (25.9)	-90.6 (23.1)

7. Secondary Outcome

Title	Number of Participants With American College of Rheumatology (ACR20) Criteria Response in Part B
Description	Defined as at least 20% improvement from the screening values in swollen and tender joint count and in 3 of the following 5 disease activity measures. Physician's global assessment of disease activity (VAS) Patient's assessment of RA pain (VAS) Patient's global assessment of disease activity Patient's assessment of physical function (Health Assessment Questionnaire) Acute phase reactant (C-reactive protein [CRP])
Time Frame	Baseline to Day 57

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population included all randomized participants regardless of the treatment actually received.

Arm/Group Title	Double Blind TL011 1000 mg	Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	25	23
Count of Participants [Participants]	14 466.7%	15 500%

8. Secondary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve [AUC (0-t)] for Part A Cohort 2
Description	Data available for cohort 2 only per planned analysis.
Time Frame	Day 1 to Day 57

Outcome Measure Data

Analysis Population Description

Pharmacokinetics (PK) population included all participants that received at least one dose of 1000 mg TL011 and had sufficient plasma concentration results to allow estimation of PK parameters.

Arm/Group Title	Cohort 2 TL011 1000 mg
Arm/Group Description	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	3
Geometric Mean (Standard Deviation) [Day*micrograms per milliliter]	6423 (1956)

9. Secondary Outcome

Title	Number of Participants With Adverse Events in Part A
Description	An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	From randomization up to Week 24

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least one dose of study drug.

Arm/Group Title	Cohort 1 TL011 500 mg	Cohort 2 TL011 1000 mg
Arm/Group Description	Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).	Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
Measure Participants	3	3
Count of Participants [Participants]	0 0%	2 66.7%

Adverse Events

Time Frame	Up to 24 weeks after first dose of study drug.
Adverse Event Reporting Description	Safety analysis set included all participants that received at least one dose of study treatment.
Arm/Group Title	Cohort 1 TL011 500 mg		Cohort 2 TL011 1000 mg		Double Blind TL011 1000 mg		Double Blind MabThera 1000 mg
Arm/Group Description	Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).		Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).		Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).		Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
All Cause Mortality
	Cohort 1 TL011 500 mg		Cohort 2 TL011 1000 mg		Double Blind TL011 1000 mg		Double Blind MabThera 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/25 (0%)		0/23 (0%)
Serious Adverse Events
	Cohort 1 TL011 500 mg		Cohort 2 TL011 1000 mg		Double Blind TL011 1000 mg		Double Blind MabThera 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		1/25 (4%)		1/23 (4.3%)
Blood and lymphatic system disorders
Sideroblastic Anaemia	0/3 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	1/23 (4.3%)	1
Ear and labyrinth disorders
Vertigo	0/3 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/23 (0%)	0
Infections and infestations
Herpes Zoster	0/3 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	Cohort 1 TL011 500 mg		Cohort 2 TL011 1000 mg		Double Blind TL011 1000 mg		Double Blind MabThera 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		2/3 (66.7%)		11/25 (44%)		5/23 (21.7%)
Cardiac disorders
Tachycardia	0/3 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	2	1/23 (4.3%)	1
General disorders
Fatigue	0/3 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	0/23 (0%)	0
Pyrexia	0/3 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	0/23 (0%)	0
Infections and infestations
Bronchitis	0/3 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	1	0/23 (0%)	0
Nasopharyngitis	0/3 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	3/23 (13%)	3
Rhinitis	0/3 (0%)	0	0/3 (0%)	0	2/25 (8%)	3	0/23 (0%)	0
Injury, poisoning and procedural complications
Infusion Related Reaction	0/3 (0%)	0	0/3 (0%)	0	2/25 (8%)	3	0/23 (0%)	0
Nervous system disorders
Headache	0/3 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	1	1/23 (4.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.