GP2013 Treatment in Patients With Active Rheumatoid Arthr... | NCT02514772

NCT02514772

Status Module

Sponsor/Collaborators Module

Name	Class
Hexal AG	INDUSTRY

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GP2013 - proposed biosimilar rituximab	Experimental	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
Originator rituximab - Rituxan ® or MabThera ®	Active Comparator	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 ®

Name	Type	Description	Arm Group Labels	Other Names
GP2013 - A Proposed biosimilar rituximab	Biological		GP2013 - proposed biosimilar rituximab
Originator rituximab - Rituxan ® or MabThera ®

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients Experiencing Anaphylactic Reactions	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	Within 24 hours of each study drug infusion: on Day 1 and Day 14
Number of Patients Experiencing Hypersensitivity Reactions	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.	24 weeks study duration
Immunogenicity	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	24 weeks study duration
Number of Patients Experiencing Potential Infusion-Related Reactions	Patients, experienced infusion related reactions repeatedly (i.e. during the first and second infusion) are counted only once in the overall line.	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)

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Sandoz Inc.	Sponsor GmbH	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Rheumatology Associates of North Alabama, PC		Huntsville	Alabama	35801	United States
Clinical and Translational Research Center of Alabama PC

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30295429	Derived	Tony HP, Kruger K, Cohen SB, Schulze-Koops H, Kivitz AJ, Jeka S, Vereckei E, Cen L, Kring L, Kollins D. Brief Report: Safety and Immunogenicity of Rituximab Biosimilar GP 2013 After Switch From Reference Rituximab in Patients With Active Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2019 Jan;71(1):88-94. doi: 10.1002/acr.23771.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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) GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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. GP2013 - A Proposed biosimilar rituximab
BG001	Rituxan ® / 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. Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera)
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

- ParticipantsBG00053
- ParticipantsBG00154
- ParticipantsBG002107

Title	Measurements
<=18 years

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Region of Enrollment

Count of Participants

Participants

Title	Denominators	Categories
United States	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Weight at screening

Mean

Standard Deviation

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Duration since initial diagnosis of rheumatoid arthritis

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

C-reactive protein (CRP) at baseline

Mean

Standard Deviation

mg/L

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Dose of methotrexate at baseline

Mean

Standard Deviation

mg/week

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Prednisone equivalent steroid dose at baseline

Steroids were not taken by all patients at the study start

Mean

Standard Deviation

mg/day

Title	Denominators	Categories
	ParticipantsBG00023 ParticipantsBG00126 ParticipantsBG002

Number of previous treatments courses with rituximab

Mean

Standard Deviation

treatment course

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Number of previous treatment courses with rituximab

Number

treatment course

Title	Denominators	Categories
1	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Experienced infusion-related reactions during rituximab treatments prior to randomization

Number

participants

Title	Denominators	Categories
No	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Anti-drug antibodies (ADA) at screening

Number

participants

Title	Denominators	Categories
Negative	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients Experiencing Anaphylactic Reactions

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

Safety Analysis Set

Posted

Count of Participants

Participants

Within 24 hours of each study drug infusion: on Day 1 and Day 14

ID	Title	Description
OG000	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. GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013
OG001	Rituxan® / 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. 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

Units	Counts
Participants	OG00053 OG00154

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0011

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Difference (%)	-1.9			2-Sided	95	-20.6	16.9					Other

Primary

Number of Patients Experiencing Hypersensitivity Reactions

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.

Safety Analysis Set

Posted

Count of Participants

Participants

24 weeks study duration

ID	Title	Description
OG000	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. GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013
OG001	Rituxan® / 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. 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

Units

Primary

Immunogenicity

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

Safety Analysis Set

Posted

Count of Participants

Participants

24 weeks study duration

ID	Title	Description
OG000	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. GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013
OG001	Rituxan® / 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. 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

Units	Counts

Primary

Number of Patients Experiencing Potential Infusion-Related Reactions

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

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.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	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. GP2013 - A Proposed biosimilar rituximab
OG001	Rituxan ® / 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. Originator rituximab - Rituxan ® or MabThera ® dependent on region of participation (USA patients receive Rituxan; EU patients receive MabThera)

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. GP2013 - A proposed biosimilar rituximab Patients in this group are switched from originator rituximab (which they received before study participation) to GP2013	0	53	0	53	19	53
EG001	Rituxan® / 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. 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	1	54	3	54	21	54

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected53 at risk EG0011 events1 affected54 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected53 at risk EG0011 events1 affected54 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected53 at risk EG0011 events1 affected54 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 affected53 at risk EG0011 events1 affected54 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 affected53 at risk EG0011 events1 affected54 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 affected53 at risk EG0011 events1 affected54 at risk
Fibrin D dimer increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected53 at risk EG0011 events1 affected54 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected53 at risk EG0012 events2 affected54 at risk
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected53 at risk EG0013 events3 affected54 at risk
Bronchitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected53 at risk EG0013 events3 affected54 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected53 at risk EG0014 events3 affected54 at risk
Nasopharyngitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0003 events2 affected53 at risk EG0011 events1 affected54 at risk
Sinusitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0002 events2 affected53 at risk EG0011 events1 affected54 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0003 events3 affected53 at risk EG0010 events0 affected54 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 events2 affected53 at risk EG0012 events2 affected54 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0003 events3 affected53 at risk EG0010 events0 affected54 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 events2 affected53 at risk EG0010 events0 affected54 at risk
Headache	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0003 events2 affected53 at risk EG0014 events2 affected54 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected53 at risk EG0012 events2 affected54 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected53 at risk EG0012 events2 affected54 at risk

ID	Term
D001172	Arthritis, Rheumatoid

Ancestor Terms

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D000069283	Rituximab

Ancestor Terms

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

Units	Counts
Participants	OG00053 OG00154