Trial Outcomes & Findings for GP2013 Treatment in Patients With Active Rheumatoid Arthritis, Previously Treated With Rituxan® or MabThera® (NCT NCT02514772)

Last Updated: 2017-12-28

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

107 participants

Primary outcome timeframe

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

Results posted on

2017-12-28

Participant Flow

Participant milestones

Participant milestones
Measure	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	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. 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
Overall Study STARTED	53	54
Overall Study COMPLETED	50	52
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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. 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
Overall Study Adverse Event	1	0
Overall Study Death	0	1
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Steroids were not taken by all patients at the study start

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GP2013 n=53 Participants 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	Rituxan ® / MabThera ® n=54 Participants 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 n=107 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=53 Participants	0 Participants n=54 Participants	0 Participants n=107 Participants
Age, Categorical Between 18 and 65 years	44 Participants n=53 Participants	39 Participants n=54 Participants	83 Participants n=107 Participants
Age, Categorical >=65 years	9 Participants n=53 Participants	15 Participants n=54 Participants	24 Participants n=107 Participants
Age, Continuous	56.8 years STANDARD_DEVIATION 9.91 • n=53 Participants	57.1 years STANDARD_DEVIATION 12.14 • n=54 Participants	57 years STANDARD_DEVIATION 11.04 • n=107 Participants
Sex: Female, Male Female	46 Participants n=53 Participants	39 Participants n=54 Participants	85 Participants n=107 Participants
Sex: Female, Male Male	7 Participants n=53 Participants	15 Participants n=54 Participants	22 Participants n=107 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=53 Participants	5 Participants n=54 Participants	9 Participants n=107 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=53 Participants	47 Participants n=54 Participants	91 Participants n=107 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=53 Participants	2 Participants n=54 Participants	7 Participants n=107 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=53 Participants	0 Participants n=54 Participants	1 Participants n=107 Participants
Race (NIH/OMB) Asian	1 Participants n=53 Participants	0 Participants n=54 Participants	1 Participants n=107 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=53 Participants	0 Participants n=54 Participants	0 Participants n=107 Participants
Race (NIH/OMB) Black or African American	0 Participants n=53 Participants	2 Participants n=54 Participants	2 Participants n=107 Participants
Race (NIH/OMB) White	51 Participants n=53 Participants	52 Participants n=54 Participants	103 Participants n=107 Participants
Race (NIH/OMB) More than one race	0 Participants n=53 Participants	0 Participants n=54 Participants	0 Participants n=107 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=53 Participants	0 Participants n=54 Participants	0 Participants n=107 Participants
Region of Enrollment United States	17 Participants n=53 Participants	18 Participants n=54 Participants	35 Participants n=107 Participants
Region of Enrollment Europe	36 Participants n=53 Participants	36 Participants n=54 Participants	72 Participants n=107 Participants
Weight at screening	80.12 kg STANDARD_DEVIATION 20.22 • n=53 Participants	81.62 kg STANDARD_DEVIATION 20.46 • n=54 Participants	80.88 kg STANDARD_DEVIATION 20.26 • n=107 Participants
Duration since initial diagnosis of rheumatoid arthritis	13.46 years STANDARD_DEVIATION 9.39 • n=53 Participants	14.01 years STANDARD_DEVIATION 8.51 • n=54 Participants	13.74 years STANDARD_DEVIATION 8.92 • n=107 Participants
C-reactive protein (CRP) at baseline	9.67 mg/L STANDARD_DEVIATION 24.25 • n=53 Participants	11.64 mg/L STANDARD_DEVIATION 23.63 • n=54 Participants	10.66 mg/L STANDARD_DEVIATION 23.84 • n=107 Participants
Dose of methotrexate at baseline	14.53 mg/week STANDARD_DEVIATION 6.203 • n=53 Participants	15.46 mg/week STANDARD_DEVIATION 5.141 • n=54 Participants	15.00 mg/week STANDARD_DEVIATION 5.684 • n=107 Participants
Prednisone equivalent steroid dose at baseline	5.39 mg/day STANDARD_DEVIATION 1.80 • n=23 Participants • Steroids were not taken by all patients at the study start	4.64 mg/day STANDARD_DEVIATION 2.36 • n=26 Participants • Steroids were not taken by all patients at the study start	4.99 mg/day STANDARD_DEVIATION 2.13 • n=49 Participants • Steroids were not taken by all patients at the study start
Number of previous treatments courses with rituximab	4.1 treatment course STANDARD_DEVIATION 3.32 • n=53 Participants	5.0 treatment course STANDARD_DEVIATION 3.75 • n=54 Participants	4.6 treatment course STANDARD_DEVIATION 3.56 • n=107 Participants
Number of previous treatment courses with rituximab 1	13 treatment course n=53 Participants	13 treatment course n=54 Participants	26 treatment course n=107 Participants
Number of previous treatment courses with rituximab >1	40 treatment course n=53 Participants	41 treatment course n=54 Participants	81 treatment course n=107 Participants
Experienced infusion-related reactions during rituximab treatments prior to randomization No	51 participants n=53 Participants	51 participants n=54 Participants	102 participants n=107 Participants
Experienced infusion-related reactions during rituximab treatments prior to randomization Yes	2 participants n=53 Participants	3 participants n=54 Participants	5 participants n=107 Participants
Anti-drug antibodies (ADA) at screening Negative	52 participants n=53 Participants	53 participants n=54 Participants	105 participants n=107 Participants
Anti-drug antibodies (ADA) at screening Positive	1 participants n=53 Participants	1 participants n=54 Participants	2 participants n=107 Participants

PRIMARY outcome

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

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	GP2013 n=53 Participants 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	Rituxan® / MabThera® n=54 Participants 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
Number of Patients Experiencing Anaphylactic Reactions	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 24 weeks study duration

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	GP2013 n=53 Participants 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	Rituxan® / MabThera® n=54 Participants 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
Number of Patients Experiencing Hypersensitivity Reactions	5 Participants	6 Participants

PRIMARY outcome

Timeframe: 24 weeks study duration

Population: Safety Analysis Set

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

Outcome measures

Outcome measures
Measure	GP2013 n=51 Participants 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	Rituxan® / MabThera® n=53 Participants 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
Immunogenicity	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 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)

Population: 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.

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

Outcome measures

Outcome measures
Measure	GP2013 n=53 Participants 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	Rituxan® / MabThera® n=54 Participants 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
Number of Patients Experiencing Potential Infusion-Related Reactions On day of or on day after first infusion	4 Participants	7 Participants
Number of Patients Experiencing Potential Infusion-Related Reactions On day of or on day after second infusion	2 Participants	5 Participants
Number of Patients Experiencing Potential Infusion-Related Reactions Overall on day(s) of or after either infusion	6 Participants	10 Participants

Adverse Events

GP2013

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Rituxan® / MabThera®

Serious events: 3 serious events

Other events: 21 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	GP2013 n=53 participants at risk 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	Rituxan® / MabThera® n=54 participants at risk 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
Cardiac disorders Atrial fibrillation	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Cardiac disorders Cardiopulmonary failure	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Gastrointestinal disorders Hiatus hernia	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Injury, poisoning and procedural complications Contusion	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Investigations Fibrin D dimer increased	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)

Other adverse events

Other adverse events
Measure	GP2013 n=53 participants at risk 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	Rituxan® / MabThera® n=54 participants at risk 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
Gastrointestinal disorders Nausea	1.9% 1/53 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	3.7% 2/54 • Number of events 2 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Gastrointestinal disorders Vomiting	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	5.6% 3/54 • Number of events 3 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Infections and infestations Bronchitis	1.9% 1/53 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	5.6% 3/54 • Number of events 3 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Infections and infestations Upper respiratory tract infection	1.9% 1/53 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	5.6% 3/54 • Number of events 4 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Infections and infestations Nasopharyngitis	3.8% 2/53 • Number of events 3 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Infections and infestations Sinusitis	3.8% 2/53 • Number of events 2 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	1.9% 1/54 • Number of events 1 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Injury, poisoning and procedural complications Fall	5.7% 3/53 • Number of events 3 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	0.00% 0/54 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	3.8% 2/53 • Number of events 2 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	3.7% 2/54 • Number of events 2 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 3/53 • Number of events 3 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	0.00% 0/54 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Musculoskeletal and connective tissue disorders Osteoarthritis	3.8% 2/53 • Number of events 2 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	0.00% 0/54 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Nervous system disorders Headache	3.8% 2/53 • Number of events 3 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	3.7% 2/54 • Number of events 4 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	3.7% 2/54 • Number of events 2 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/53 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)	3.7% 2/54 • Number of events 2 • Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 24)

Additional Information

Global Program Medical Director

Sandoz

Phone: +49 8024 476

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER