ASSIST-RT: GP2013 Treatment in Patients With Active Rheumatoid Arthritis, Previously Treated With Rituxan® or MabThera®

• Sponsor: Sandoz (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02514772
• Collaborator: Hexal AG (Industry)
• Enrollment: 107
• Locations: 65
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study objective is to identify potential safety risks of the transition from US-licensed Rituxan® or EU-approved MabThera® to GP2013 (proposed biosimilar product) as compared to continuous treatment with the originator product in terms of general safety and immunogenicity.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: GP2013 - A Proposed biosimilar rituximab; Biological: Originator rituximab - Rituxan ® or MabThera ®	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double- Blind, Controlled, Parallel-group, Multicenter Study to Assess the Safety and Immunogenicity of Transitioning to GP2013 or Re-treatment With Rituxan® or MabThera® in Patients With Active Rheumatoid Arthritis, Previously Treated With Rituxan® or MabThera®
• Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GP2013 - proposed biosimilar rituximab 10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. The treatment course consists of 2 i.v. infusions 2 weeks apart (at Day 1 and Day 14).	Biological: GP2013 - A Proposed biosimilar rituximab
Active Comparator: Originator rituximab - Rituxan ® or MabThera ® 10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. The treatment course consists of 2 i.v. infusions 2 weeks apart (at Day 1 and Day 14).	Biological: Originator rituximab - Rituxan ® or MabThera ®

Outcome Measures

Primary Outcome Measures

1. Number of Patients Experiencing Anaphylactic Reactions [Within 24 hours of each study drug infusion: on Day 1 and Day 14]

   2006 NIAID/FAAN* criteria were used for identification of anaphylactic reactions within 24h of each study drug infusion. For patients with no history of infusion-related reactions during their previous treatments with rituximab, symptoms/signs in at least 2 out of 4 organ systems: Skin/mucosal tissue Respiratory organs Drop of systolic blood pressure (<90 mmHg or variance from baseline >30%) or associated symptoms Gastrointestinal organs were defined as an anaphylactic reaction. The same criteria were also applied to patients with history of infusion-related reactions during their previous treatments with rituximab. In addition, if these patients experienced only a rapid drop in systolic blood pressure (<90 mmHg or variance from baseline >30%), this was defined as an anaphylactic reaction disregarding involvement of other organ systems. * NIAID - National Institute of Allergy and Infectious Diseases FAAN - Food Allergy and Anaphylaxis Network

2. Number of Patients Experiencing Hypersensitivity Reactions [24 weeks study duration]

   The standardized MedDRA query (SMQ) - Hypersensitivity reactions (SMQ 20000214) was used for the identification of hypersensitivity reactions overall from first infusion in the adverse event database.

3. Immunogenicity [24 weeks study duration]

   Number of patients tested positive for anti-drug-antibodies (ADA) post-randomization. Patients with negative ADA results at screening and at least one evaluable post-randomization ADA assessment are included in the analysis

4. Number of Patients Experiencing Potential Infusion-Related Reactions [On the day of and on the day after each study drug infusion (e.g. on study day 1 and 2 for the 1st study drug infusion and on study day 14 and 15 for the 2nd study drug infusion, if the second drug infusion was given on study day 14)]

   Patients, experienced infusion related reactions repeatedly (i.e. during the first and second infusion) are counted only once in the overall line.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis (RA) according to ACR 2010 criteria

• Completed one full treatment course with either Rituxan® or MabThera®

• Eligible for a further treatment course with Rituxan® or MabThera®- Currently treated with methotrexate

Exclusion Criteria:

• RA functional status class IV (ACR 1991 revised criteria)

• Systemic manifestation of RA

• Positive serology for hepatitis B or hepatitis C infection

• Active systemic infection

• History of cancer

• Known severely immunocompromised state

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rheumatology Associates of North Alabama, PC	Huntsville	Alabama	United States	35801
2	Clinical and Translational Research Center of Alabama PC	Tuscaloosa	Alabama	United States	35406
3	Arizona Arthritis & Rheumatology Research, PLLC	Glendale	Arizona	United States	85306
4	Arizona Arthritis and Rheumatology Research, PLLC	Mesa	Arizona	United States	85202
5	Arizona Arthritis & Rheumatology Research, PLLC	Phoenix	Arizona	United States	85032
6	Arizona Arthritis and Rheumatology Research, PLLC	Phoenix	Arizona	United States	85037
7	TriWest Research Associates, LLC	El Cajon	California	United States	92020
8	Valerius Medical Group and Research Center of Greater Long Beach, Inc	Long Beach	California	United States	90806
9	Pacific Arthritis Center Medical Group	Santa Maria	California	United States	93454
10	Westlake Medical Research Inc.	Thousand Oaks	California	United States	91360
11	Inland Rheumatology and Osteoporosis Medical Group	Upland	California	United States	91786
12	Arthritis Associates & Osteoporosis Center of Colorado Springs	Colorado Springs	Colorado	United States	80920
13	Denver Arthritis Clinic	Denver	Colorado	United States	80230
14	Bay Area Arthritis and Osteoporosis	Brandon	Florida	United States	33511
15	Sunrise Research Institute, Inc.	Miami	Florida	United States	33130
16	Omega Research Consultants, LLC	Orlando	Florida	United States	32804
17	Arthritis Center	Palm Harbor	Florida	United States	34684
18	Arthritis Research of Florida, Inc.	Palm Harbor	Florida	United States	34684
19	Southwest Florida Clinical Research Center	Tampa	Florida	United States	33609
20	Florida Medical Clinic, PA	Zephyrhills	Florida	United States	33542
21	Idaho Arthritis and Osteoporosis Clinic	Meridian	Idaho	United States	83642
22	Bluegrass Community Research, Inc.	Lexington	Kentucky	United States	40504
23	Arthritis and Rheumatology Consultants, P.A.	Edina	Minnesota	United States	55435
24	North Mississippi Medical Clinical, Inc	Tupelo	Mississippi	United States	38801
25	Physician Research Collaboration, LLC	Lincoln	Nebraska	United States	68516
26	Innovative Health Research	Las Vegas	Nevada	United States	89128
27	Arthritis and Osteoporosis Consultants of The Carolinas	Charlotte	North Carolina	United States	28207
28	Physicians East, PA	Greenville	North Carolina	United States	27834
29	STAT Research Inc.	Dayton	Ohio	United States	45417
30	Arthritis & Rheumatology Center of Oklahoma, PLLC	Oklahoma City	Oklahoma	United States	73103
31	Health Research of Oklahoma	Oklahoma City	Oklahoma	United States	73103
32	Altoona Center For Clinical Research	Duncansville	Pennsylvania	United States	16635
33	Emkey Arthritis and Osteoporosis Clinic, PC	Wyomissing	Pennsylvania	United States	19610
34	Low Country Rheumatology, PA	Charleston	South Carolina	United States	29406
35	Piedmont Arthritis Clinic, PA	Greenville	South Carolina	United States	29601
36	Amarillo Center for Clinical Research, Ltd.	Amarillo	Texas	United States	79124
37	Pioneer Research Solutions, Inc.	Houston	Texas	United States	77099
38	Arthritis and Osteoporosis Center of South Texas	San Antonio	Texas	United States	78232
39	Rheumatic Disease Center	Glendale	Wisconsin	United States	53217
40	Praxis Prof. Herbert Kellner	München	Bayern	Germany	80639
41	Praxiszentrum St. Bonifatius	München	Bayern	Germany	81541
42	Rheumahaus - GbR	Potsdam	Brandenburg	Germany	14469
43	Universitätsklinikum Frankfurt	Frankfurt am Main	Hessen	Germany	60528
44	Gemeinschaftspraxis Dr. von Hinüber, Dr. Demary	Hildesheim	Niedersachsen	Germany	31134
45	Klinikum Porz am Rhein	Köln	Nordrhein-Westfalen	Germany	51149
46	Schwerpunktpraxis Rheumatologie	Rendsburg	Schleswig-Holstein	Germany	24768
47	MVZ Ambulantes Rheumazentrum Erfurt	Erfurt	Thüringen	Germany	99096
48	Rheumatology Center Prof. Neeck	Bad Doberan		Germany	18209
49	Rheumapraxis Steglitz	Berlin		Germany	12161
50	Immanuel Krankenhaus Berlin, Standort Berlin-Buch	Berlin		Germany	13125
51	Rheumatologisches MVZ Dresden GmbH	Dresden		Germany	01109
52	Rheumatologie im Struensee-Haus	Hamburg		Germany	22767
53	LMU Klinikum der Universität München	München		Germany	80336
54	Studienambulanz Dr. Wassenberg	Ratingen		Germany	40882
55	Universitätsklinikum Würzburg	Würzburg		Germany	97080
56	Országos Reumatológiai És Fizioterápiás Intézet	Budapest		Hungary	1023
57	QUALICLINIC Kft	Budapest		Hungary	1036
58	Csongrád Megyei Dr. Bugyi István Kórház	Szentes		Hungary	6600
59	MÁV Kórház és Rendelőintézet Szolnok	Szolnok		Hungary	5000
60	Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy	Bydgoszcz		Poland	85-168
61	Twoja Przychodnia - Centrum Medyczne Nowa Sol	Nowa Sol		Poland	67 -100
62	Slaskie Centrum Reumatologii, Rehabilitacji i Zapobiegania Niepelnosprawnosci im gen. Jerzego Zietka	Ustron		Poland	43-450
63	Linea Corporis Chirurgia Plastyczna	Warszawa		Poland	00-235
64	Medycyna Kliniczna Marzena Waszczak	Warszawa		Poland	00660
65	Centrum Medyczne AMED	Warszawa		Poland	01-518

Sponsors and Collaborators

• Sandoz
• Hexal AG

Investigators

• Study Chair: Sandoz Inc., Sponsor GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT02514772
• Other Study ID Numbers: GP13-302
• First Posted: Aug 4, 2015
• Last Update Posted: Dec 28, 2017
• Last Verified: Nov 1, 2017

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

Study Results

Participant Flow

Arm/Group Title	GP2013	Rituxan® / MabThera®
Arm/Group Description	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. The treatment course consists of 2 i.v. infusions 2 weeks apart (at Day 1 and Day 14) GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. The treatment course consists of 2 i.v. infusions 2 weeks apart (at Day 1 and Day 14) Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera). Patients in this group receive same originator rituximab as they received before study participation
Period Title: Overall Study
STARTED	53	54
COMPLETED	50	52
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	GP2013	Rituxan ® / MabThera ®	Total
Arm/Group Description	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. GP2013 - A Proposed biosimilar rituximab	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera)	Total of all reporting groups
Overall Participants	53	54	107
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	44 83%	39 72.2%	83 77.6%
>=65 years	9 17%	15 27.8%	24 22.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.8 (9.91)	57.1 (12.14)	57 (11.04)
Sex: Female, Male (Count of Participants)
Female	46 86.8%	39 72.2%	85 79.4%
Male	7 13.2%	15 27.8%	22 20.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 7.5%	5 9.3%	9 8.4%
Not Hispanic or Latino	44 83%	47 87%	91 85%
Unknown or Not Reported	5 9.4%	2 3.7%	7 6.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.9%	0 0%	1 0.9%
Asian	1 1.9%	0 0%	1 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 3.7%	2 1.9%
White	51 96.2%	52 96.3%	103 96.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	17 32.1%	18 33.3%	35 32.7%
Europe	36 67.9%	36 66.7%	72 67.3%
Weight at screening (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	80.12 (20.22)	81.62 (20.46)	80.88 (20.26)
Duration since initial diagnosis of rheumatoid arthritis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.46 (9.39)	14.01 (8.51)	13.74 (8.92)
C-reactive protein (CRP) at baseline (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	9.67 (24.25)	11.64 (23.63)	10.66 (23.84)
Dose of methotrexate at baseline (mg/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/week]	14.53 (6.203)	15.46 (5.141)	15.00 (5.684)
Prednisone equivalent steroid dose at baseline (mg/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/day]	5.39 (1.80)	4.64 (2.36)	4.99 (2.13)
Number of previous treatments courses with rituximab (treatment course) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [treatment course]	4.1 (3.32)	5.0 (3.75)	4.6 (3.56)
Number of previous treatment courses with rituximab (treatment course) [Number]
1	13	13	26
>1	40	41	81
Experienced infusion-related reactions during rituximab treatments prior to randomization (participants) [Number]
No	51 96.2%	51 94.4%	102 95.3%
Yes	2 3.8%	3 5.6%	5 4.7%
Anti-drug antibodies (ADA) at screening (participants) [Number]
Negative	52 98.1%	53 98.1%	105 98.1%
Positive	1 1.9%	1 1.9%	2 1.9%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Experiencing Anaphylactic Reactions
Description	2006 NIAID/FAAN* criteria were used for identification of anaphylactic reactions within 24h of each study drug infusion. For patients with no history of infusion-related reactions during their previous treatments with rituximab, symptoms/signs in at least 2 out of 4 organ systems: Skin/mucosal tissue Respiratory organs Drop of systolic blood pressure (<90 mmHg or variance from baseline >30%) or associated symptoms Gastrointestinal organs were defined as an anaphylactic reaction. The same criteria were also applied to patients with history of infusion-related reactions during their previous treatments with rituximab. In addition, if these patients experienced only a rapid drop in systolic blood pressure (<90 mmHg or variance from baseline >30%), this was defined as an anaphylactic reaction disregarding involvement of other organ systems. * NIAID - National Institute of Allergy and Infectious Diseases FAAN - Food Allergy and Anaphylaxis Network
Time Frame	Within 24 hours of each study drug infusion: on Day 1 and Day 14

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	GP2013	Rituxan® / MabThera®
Arm/Group Description	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera). Patients in this group receive same originator rituximab as they received before study participation
Measure Participants	53	54
Count of Participants [Participants]	0 0%	1 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2013, Rituxan® / MabThera®
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -20.6 to 16.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Patients Experiencing Hypersensitivity Reactions
Description	The standardized MedDRA query (SMQ) - Hypersensitivity reactions (SMQ 20000214) was used for the identification of hypersensitivity reactions overall from first infusion in the adverse event database.
Time Frame	24 weeks study duration

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	GP2013	Rituxan® / MabThera®
Arm/Group Description	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera). Patients in this group receive same originator rituximab as they received before study participation
Measure Participants	53	54
Count of Participants [Participants]	5 9.4%	6 11.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2013, Rituxan® / MabThera®
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -20.6 to 16.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Immunogenicity
Description	Number of patients tested positive for anti-drug-antibodies (ADA) post-randomization. Patients with negative ADA results at screening and at least one evaluable post-randomization ADA assessment are included in the analysis
Time Frame	24 weeks study duration

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	GP2013	Rituxan® / MabThera®
Arm/Group Description	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera). Patients in this group receive same originator rituximab as they received before study participation
Measure Participants	51	53
Count of Participants [Participants]	0 0%	1 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2013, Rituxan® / MabThera®
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (%)
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -21.2 to 17.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Patients Experiencing Potential Infusion-Related Reactions
Description	Patients, experienced infusion related reactions repeatedly (i.e. during the first and second infusion) are counted only once in the overall line.
Time Frame	On the day of and on the day after each study drug infusion (e.g. on study day 1 and 2 for the 1st study drug infusion and on study day 14 and 15 for the 2nd study drug infusion, if the second drug infusion was given on study day 14)

Outcome Measure Data

Analysis Population Description

The total number of patients, who received second infusion in GP2013 arm differs from the total number of patients in GP2013 arm due to patients withdrawn after the 1st infusion.

Arm/Group Title	GP2013	Rituxan ® / MabThera ®
Arm/Group Description	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. GP2013 - A Proposed biosimilar rituximab	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera)
Measure Participants	53	54
On day of or on day after first infusion	4 7.5%	7 13%
On day of or on day after second infusion	2 3.8%	5 9.3%
Overall on day(s) of or after either infusion	6 11.3%	10 18.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2013, Rituxan® / MabThera®
	Comments	Incidence difference of infusion-related reactions, occurred on day of or on day after first infusion (i.e. on study day 1 or on study day 2).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.4
	Confidence Interval	(2-Sided) 95%; -24.2 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GP2013, Rituxan® / MabThera®
	Comments	Incidence difference of infusion-related reactions, occurred on day of or on day after second infusion (i.e. on study day 14 or on study day 15).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.3
	Confidence Interval	(2-Sided) 95%; -24.5 to 13.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GP2013, Rituxan® / MabThera®
	Comments	Incidence difference of infusion-related reactions overall on day(s) of or day(s) after either infusion (i.e. on day 1 or 2 and on day 14 or day 15).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.2
	Confidence Interval	(2-Sided) 95%; -26.0 to 11.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Arm/Group Title	GP2013		Rituxan® / MabThera®
Arm/Group Description	10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013		10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera). Patients in this group receive same originator rituximab as they received before study participation
All Cause Mortality
	GP2013		Rituxan® / MabThera®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		1/54 (1.9%)
Serious Adverse Events
	GP2013		Rituxan® / MabThera®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		3/54 (5.6%)
Cardiac disorders
Atrial fibrillation	0/53 (0%)		1/54 (1.9%)	1
Cardiopulmonary failure	0/53 (0%)		1/54 (1.9%)	1
Gastrointestinal disorders
Hiatus hernia	0/53 (0%)		1/54 (1.9%)	1
Injury, poisoning and procedural complications
Contusion	0/53 (0%)		1/54 (1.9%)	1
Humerus fracture	0/53 (0%)		1/54 (1.9%)	1
Pelvic fracture	0/53 (0%)		1/54 (1.9%)	1
Investigations
Fibrin D dimer increased	0/53 (0%)		1/54 (1.9%)	1
Other (Not Including Serious) Adverse Events
	GP2013		Rituxan® / MabThera®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/53 (35.8%)		21/54 (38.9%)
Gastrointestinal disorders
Nausea	1/53 (1.9%)	1	2/54 (3.7%)	2
Vomiting	0/53 (0%)	0	3/54 (5.6%)	3
Infections and infestations
Bronchitis	1/53 (1.9%)	1	3/54 (5.6%)	3
Upper respiratory tract infection	1/53 (1.9%)	1	3/54 (5.6%)	4
Nasopharyngitis	2/53 (3.8%)	3	1/54 (1.9%)	1
Sinusitis	2/53 (3.8%)	2	1/54 (1.9%)	1
Injury, poisoning and procedural complications
Fall	3/53 (5.7%)	3	0/54 (0%)	0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	2/53 (3.8%)	2	2/54 (3.7%)	2
Arthralgia	3/53 (5.7%)	3	0/54 (0%)	0
Osteoarthritis	2/53 (3.8%)	2	0/54 (0%)	0
Nervous system disorders
Headache	2/53 (3.8%)	3	2/54 (3.7%)	4
Respiratory, thoracic and mediastinal disorders
Cough	0/53 (0%)	0	2/54 (3.7%)	2
Skin and subcutaneous tissue disorders
Pruritus	0/53 (0%)	0	2/54 (3.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Sponsor shall have the right to the first publication or presentation of the results of the study which is intended to be a joint, multi-center publication of the study results. Following the first publication, institutions and/or Principal Investigators may publish or present data or results from the study per the terms of the clinical trial agreement.