Trial Outcomes & Findings for A Phase 3 Study of NI-071 in Participants With Rheumatoid Arthritis (RADIANCE) (NCT NCT02990806)

Last Updated: 2023-01-30

Results Overview

ACR20 was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 20% improvement from baseline in the tender/painful joint count. ii) A 20% improvement from baseline in the swollen joint count. iii) A 20% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity visual analog scale (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS) (0= no symptoms;100=severe symptoms), c) Participant pain assessment (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), d) Health Assessment Questionnaire-Disability Index (HAQ-DI), total score ranging from 0-3 with lower scores meaning less disability, e) CRP.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

683 participants

Primary outcome timeframe

At Week 22

Results posted on

2023-01-30

Participant Flow

Participants were enrolled from 97 investigative site in Czech Republic, Poland, Russia, Spain, Ukraine, and the United States in the study from 19 January 2017 to 20 May 2019.

The study consisted of 3 stages: the biosimilarity stage (Stage 1), the interchangeability stage (Stage 2), and the safety follow-up stage (Stage 3). A total of 683 participants were randomized in a 2:1 ratio to the Remicade-US and NI-071 groups during Stage 1. In Stage 2 participants in the original Remicade-US group were re-randomized (1:1) to a Remicade-US group and a Switch group (to assess the effects of switching between Remicade-US and NI-071).

Participant milestones

Participant milestones
Measure	Stage 1 and 2: NI-071 Group Participants received intravenous (IV) infusion of NI-071 at a dose of 3 milligrams/kilograms (mg/kg) at Weeks 0, 2, 6, 14 during stage 1 and at Weeks 22, 30, 38, 46, and 54 during stage 2. Participants were followed up to Week 62 during safety follow-up.	Stage 1: Remicade-US Group Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Remicade-US Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 to continue Remicade-US dose 3 mg/kg from Week 22 through Week 54 with every 8 weeks dosing intervals. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1 (22 Weeks) STARTED	228	455	0	0
Stage 1 (22 Weeks) Safety Population	227	451	0	0
Stage 1 (22 Weeks) COMPLETED	214	399	0	0
Stage 1 (22 Weeks) NOT COMPLETED	14	56	0	0
Stage 2 (32 Weeks) STARTED	214	0	201	196
Stage 2 (32 Weeks) COMPLETED	172	0	173	162
Stage 2 (32 Weeks) NOT COMPLETED	42	0	28	34
Stage 3 (Safety Follow-up) (8 Weeks) STARTED	172	0	173	162
Stage 3 (Safety Follow-up) (8 Weeks) COMPLETED	163	0	162	152
Stage 3 (Safety Follow-up) (8 Weeks) NOT COMPLETED	9	0	11	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Stage 1 and 2: NI-071 Group Participants received intravenous (IV) infusion of NI-071 at a dose of 3 milligrams/kilograms (mg/kg) at Weeks 0, 2, 6, 14 during stage 1 and at Weeks 22, 30, 38, 46, and 54 during stage 2. Participants were followed up to Week 62 during safety follow-up.	Stage 1: Remicade-US Group Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Remicade-US Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 to continue Remicade-US dose 3 mg/kg from Week 22 through Week 54 with every 8 weeks dosing intervals. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1 (22 Weeks) Adverse Event	1	15	0	0
Stage 1 (22 Weeks) Physician Decision	1	1	0	0
Stage 1 (22 Weeks) Initiated protocol-prohibited medication	2	2	0	0
Stage 1 (22 Weeks) Noncompliant with visit schedule and/or protocol	2	2	0	0
Stage 1 (22 Weeks) Lost to Follow-up	2	2	0	0
Stage 1 (22 Weeks) Withdrawal by Subject	4	26	0	0
Stage 1 (22 Weeks) Lack of Efficacy	1	2	0	0
Stage 1 (22 Weeks) Death	0	1	0	0
Stage 1 (22 Weeks) Required antibiotics resulting in drug interruption >2 weeks	0	1	0	0
Stage 1 (22 Weeks) Protocol deviation	0	1	0	0
Stage 1 (22 Weeks) Other	1	3	0	0
Stage 2 (32 Weeks) Adverse Event	9	0	7	7
Stage 2 (32 Weeks) Death	1	0	0	0
Stage 2 (32 Weeks) Physician Decision	3	0	1	0
Stage 2 (32 Weeks) Diagnosed with malignancy	1	0	0	1
Stage 2 (32 Weeks) Required antibiotics resulting in drug interruption	1	0	1	1
Stage 2 (32 Weeks) Initiated protocol-prohibited medication	1	0	0	2
Stage 2 (32 Weeks) Noncompliant with visit schedule and/or protocol	2	0	6	5
Stage 2 (32 Weeks) Lost to Follow-up	1	0	1	2
Stage 2 (32 Weeks) Protocol deviation	2	0	2	3
Stage 2 (32 Weeks) Withdrawal by Subject	14	0	4	8
Stage 2 (32 Weeks) Lack of Efficacy	4	0	2	3
Stage 2 (32 Weeks) Other	3	0	4	1
Stage 2 (32 Weeks) Ineligible according to Tuberculosis (TB) criteria	0	0	0	1
Stage 3 (Safety Follow-up) (8 Weeks) Adverse Event	5	0	4	3
Stage 3 (Safety Follow-up) (8 Weeks) Physician Decision	1	0	1	1
Stage 3 (Safety Follow-up) (8 Weeks) Noncompliant with visit schedule and/or protocol	2	0	2	2
Stage 3 (Safety Follow-up) (8 Weeks) Lost to Follow-up	1	0	0	1
Stage 3 (Safety Follow-up) (8 Weeks) Withdrawal by Subject	0	0	2	1
Stage 3 (Safety Follow-up) (8 Weeks) Lack of Efficacy	0	0	1	0
Stage 3 (Safety Follow-up) (8 Weeks) Other	0	0	0	2
Stage 3 (Safety Follow-up) (8 Weeks) Initiated protocol-prohibited medication	0	0	1	0

Baseline Characteristics

A Phase 3 Study of NI-071 in Participants With Rheumatoid Arthritis (RADIANCE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stage 1: NI-071 Group n=228 Participants Participants received intravenous (IV) infusion of NI-071 at a dose of 3 milligrams/kilograms (mg/kg) at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=455 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Total n=683 Participants Total of all reporting groups
Age, Continuous	53.3 years STANDARD_DEVIATION 12.0 • n=5 Participants	53.7 years STANDARD_DEVIATION 11.9 • n=7 Participants	53.6 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	173 Participants n=5 Participants	372 Participants n=7 Participants	545 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	83 Participants n=7 Participants	138 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	50 Participants n=5 Participants	103 Participants n=7 Participants	153 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	174 Participants n=5 Participants	350 Participants n=7 Participants	524 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	25 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) White	211 Participants n=5 Participants	424 Participants n=7 Participants	635 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 22

Population: The Intent to Treat (ITT) included all participants who were randomized, irrespective of any deviation from the protocol or premature discontinuation. Data for this outcome measure was planned to be collected and analyzed for Stage 1.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=228 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=455 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR20-CRP) Response Rate at Week 22	56.6 percentage of participants Interval 50.1 to 63.0	53.0 percentage of participants Interval 48.4 to 57.6	—	—

PRIMARY outcome

Timeframe: Week 46: Pre-dose, 1 hour after infusion, at end of infusion, at 4 hours and 24 hours after infusion and at Week 47, Week 48, Week 50, Week 52, and Week 54 post-dose

Population: Pharmacokinetic (PK) population included all participants in the full analysis set (FAS) in Stage 1 who have valid PK assessments through Stage 2. The FAS included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Stage 1.

AUCtau of NI-071 and Remicade US in stage 2 and 3 was reported. As this was an interchangeability study, the NI-071 and Remicade only were the comparators and then switch study showed same measurement in relationship to the non-switched participants. Hence, combined data was assessed and collected in participants from Remicade US to Switch Group.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=149 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=146 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=135 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Area Under the Serum Concentration-time Curve Interval (AUCtau) of NI-071 and Remicade US	12949622.78 hournanograms per milliliter (hng/mL) Standard Deviation 6999387.76	12859923.90 hournanograms per milliliter (hng/mL) Standard Deviation 8228379.79	12040415.23 hournanograms per milliliter (hng/mL) Standard Deviation 6624933.11	—

PRIMARY outcome

Timeframe: Week 46: Pre-dose, 1 hour after infusion, at end of infusion, at 4 hours and 24 hours after infusion and at Week 47, Week 48, Week 50, Week 52, and Week 54 post-dose

Population: PK population included all participants in the FAS in Stage 1 who have valid PK assessments through Stage 2. The FAS included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Stage 1.

Cmax of NI-071 and Remicade US was reported. As this was an interchangeability study, the NI-071 and Remicade only were the comparators and then switch study showed same measurement in relationship to the non-switched participants. Hence, combined data was assessed and collected in participants from Remicade US to Switch Group.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=159 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=155 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=146 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Maximum Observed Serum Concentration (Cmax) of NI-071 and Remicade US	66298.1 nanograms per milliliter (ng/mL) Standard Deviation 21756.8	63649.0 nanograms per milliliter (ng/mL) Standard Deviation 16566.2	61660.8 nanograms per milliliter (ng/mL) Standard Deviation 18696.5	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 6, 14, 18, and 22

Population: The FAS population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable at specific time point.

The DAS28-CRP was a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints \[assessed on 2-point scale (0=absent; 1=present\]), swollen joint count (out of 28 evaluated joints\[assessed on 2-point scale (0=absent; 1=present)\]), Participant's global assessment of disease activity (assessed on 0-100 mm VAS; where higher scores denotes severe symptoms), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Total Scores on the DAS28-CRP range from 0 to approximately 10 (0=very good, no symptoms; 10=very poor, severe symptoms), where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 2, 6, 14, 18, and 22 Baseline	5.816 score on a scale Standard Deviation 0.822	5.898 score on a scale Standard Deviation 0.787	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 2, 6, 14, 18, and 22 Change at Week 2	-1.094 score on a scale Standard Deviation 0.881	-1.169 score on a scale Standard Deviation 0.931	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 2, 6, 14, 18, and 22 Change at Week 6	-1.542 score on a scale Standard Deviation 1.041	-1.650 score on a scale Standard Deviation 1.114	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 2, 6, 14, 18, and 22 Change at Week 14	-1.828 score on a scale Standard Deviation 1.137	-1.812 score on a scale Standard Deviation 1.221	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 2, 6, 14, 18, and 22 Change at Week 18	-2.070 score on a scale Standard Deviation 1.159	-2.156 score on a scale Standard Deviation 1.193	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 2, 6, 14, 18, and 22 Change at Week 22	-1.835 score on a scale Standard Deviation 1.247	-1.978 score on a scale Standard Deviation 1.209	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=212 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=198 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=194 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 46	-2.242 score on a scale Standard Deviation 1.203	-2.387 score on a scale Standard Deviation 1.270	-2.207 score on a scale Standard Deviation 1.217	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 50	-2.444 score on a scale Standard Deviation 1.156	-2.679 score on a scale Standard Deviation 1.245	-2.551 score on a scale Standard Deviation 1.172	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 54	-2.443 score on a scale Standard Deviation 1.212	-2.462 score on a scale Standard Deviation 1.189	-2.247 score on a scale Standard Deviation 1.298	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 58	-2.568 score on a scale Standard Deviation 1.211	-2.739 score on a scale Standard Deviation 1.236	-2.450 score on a scale Standard Deviation 1.227	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 62	-2.466 score on a scale Standard Deviation 1.238	-2.605 score on a scale Standard Deviation 1.276	-2.404 score on a scale Standard Deviation 1.327	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 26	-2.199 score on a scale Standard Deviation 1.238	-2.317 score on a scale Standard Deviation 1.227	-2.192 score on a scale Standard Deviation 1.180	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 30	-2.106 score on a scale Standard Deviation 1.269	-2.298 score on a scale Standard Deviation 1.251	-2.092 score on a scale Standard Deviation 1.230	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 34	-2.379 score on a scale Standard Deviation 1.251	-2.586 score on a scale Standard Deviation 1.187	-2.446 score on a scale Standard Deviation 1.266	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 38	-2.281 score on a scale Standard Deviation 1.234	-2.331 score on a scale Standard Deviation 1.258	-2.321 score on a scale Standard Deviation 1.376	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 42	-2.415 score on a scale Standard Deviation 1.228	-2.630 score on a scale Standard Deviation 1.226	-2.519 score on a scale Standard Deviation 1.236	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 6, 14, 18, and 22

DAS28 is a measure of disease activity in participants with rheumatoid arthritis, derived using differential weighting given to each of the four components. The components of the DAS28 (ESR) assessment included: TJC with 28 joints assessed, SJC with 28 joints assessed, ESR (millimeters per hour) and GH recorded on 100mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). DAS28 (ESR) was calculated as 0.56\*sqrt (TJC28) + 0.28\*sqrt (SJC28) + 0.70\*ln(ESR \[mm/hour\] + 0.014\*GH \[mm\]; where, TJC28 = number of painful joints out of 28 joints, SJC28 = number of swollen joints out of 28 joints, GH = score of the participant global assessment of disease activity, ln = natural logarithm, sqrt = square root of. Total score range: 0 to 9.4, higher score indicated more disease activity. A negative change from baseline indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=445 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 6, 14, 18, and 22 Baseline	6.552 score on a scale Standard Deviation 0.861	6.655 score on a scale Standard Deviation 0.755	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 6, 14, 18, and 22 Change at Week 2	-1.060 score on a scale Standard Deviation 0.915	-1.161 score on a scale Standard Deviation 0.893	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 6, 14, 18, and 22 Change at Week 6	-1.588 score on a scale Standard Deviation 1.112	-1.778 score on a scale Standard Deviation 1.174	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 6, 14, 18, and 22 Change at Week 14	-2.002 score on a scale Standard Deviation 1.254	-1.951 score on a scale Standard Deviation 1.266	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 6, 14, 18, and 22 Change at Week 18	-2.291 score on a scale Standard Deviation 1.300	-2.345 score on a scale Standard Deviation 1.278	—	—
Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 6, 14, 18, and 22 Change at Week 22	-2.060 score on a scale Standard Deviation 1.386	-2.195 score on a scale Standard Deviation 1.326	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

DAS28 is a measure of disease activity in participants with rheumatoid arthritis, derived using differential weighting given to each of the four components. The components of the DAS28 (ESR) assessment included: TJC with 28 joints assessed, SJC with 28 joints assessed, ESR (millimeters per hour) and Patient Global Assessment (PtGA) recorded on 100mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). DAS28 (ESR) was calculated as 0.56\*sqrt (TJC28) + 0.28\*sqrt (SJC28) + 0.70\*ln(ESR \[mm/hour\] + 0.014\*GH \[mm\]; where, TJC28 = number of painful joints out of 28 joints, SJC28 = number of swollen joints out of 28 joints, GH = score of the participant global assessment of disease activity, ln = natural logarithm, sqrt = square root of. Total score range: 0 to 9.4, higher score indicated more disease activity. A negative change from baseline indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=212 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=198 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=193 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 26	-2.387 score on a scale Standard Deviation 1.393	-2.533 score on a scale Standard Deviation 1.395	-2.375 score on a scale Standard Deviation 1.304	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 30	-2.346 score on a scale Standard Deviation 1.457	-2.533 score on a scale Standard Deviation 1.349	-2.261 score on a scale Standard Deviation 1.374	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 34	-2.602 score on a scale Standard Deviation 1.416	-2.864 score on a scale Standard Deviation 1.303	-2.609 score on a scale Standard Deviation 1.376	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 38	-2.516 score on a scale Standard Deviation 1.478	-2.535 score on a scale Standard Deviation 1.314	-2.493 score on a scale Standard Deviation 1.518	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 42	-2.650 score on a scale Standard Deviation 1.372	-2.847 score on a scale Standard Deviation 1.258	-2.691 score on a scale Standard Deviation 1.433	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 46	-2.494 score on a scale Standard Deviation 1.352	-2.625 score on a scale Standard Deviation 1.322	-2.406 score on a scale Standard Deviation 1.364	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 50	-2.649 score on a scale Standard Deviation 1.291	-2.964 score on a scale Standard Deviation 1.302	-2.708 score on a scale Standard Deviation 1.303	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 54	-2.619 score on a scale Standard Deviation 1.385	-2.662 score on a scale Standard Deviation 1.221	-2.403 score on a scale Standard Deviation 1.410	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 58	-2.764 score on a scale Standard Deviation 1.385	-2.985 score on a scale Standard Deviation 1.337	-2.617 score on a scale Standard Deviation 1.376	—
Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 62	-2.663 score on a scale Standard Deviation 1.439	-2.864 score on a scale Standard Deviation 1.371	-2.574 score on a scale Standard Deviation 1.470	—

SECONDARY outcome

Timeframe: At Weeks 2, 6, 14, 18, and 22

Population: The FAS population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. Last observation carried forward (LOCF) method was used to carry forward any of the individually missing component values, and from that mix of actual and carried-forward values, the ACR responder status was determined.

ACR20 was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 20% improvement from baseline in the tender/painful joint count. ii) A 20% improvement from baseline in the swollen joint count. iii) A 20% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3 with lower scores meaning less disability, e) CRP.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 2	31.3 percentage of participants Interval 25.2 to 37.3	32.5 percentage of participants Interval 28.2 to 36.9	—	—
Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 6	47.1 percentage of participants Interval 40.6 to 53.6	54.3 percentage of participants Interval 49.6 to 58.9	—	—
Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 14	56.4 percentage of participants Interval 49.9 to 62.8	51.1 percentage of participants Interval 46.5 to 55.8	—	—
Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 18	62.6 percentage of participants Interval 56.3 to 68.9	61.7 percentage of participants Interval 57.1 to 66.2	—	—
Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 22	56.8 percentage of participants Interval 50.4 to 63.3	54.5 percentage of participants Interval 49.9 to 59.1	—	—

SECONDARY outcome

Timeframe: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

Population: Full Analysis Set population included participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Overall Number of Participants indicates the number of patients with FAS. The patient number of FAS is the number of patients evaluated at baseline, which is different from number of patients who started Stage 2 or 3. ACR 20 (CRP) response rate/visit was calculated based on the number of patients achieving ACR20 criteria divided by FAS number.

ACR20 was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 20% improvement from baseline in the tender/painful joint count. ii) A 20% improvement from baseline in the swollen joint count. iii) A 20% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3 with lower scores meaning less disability, e) CRP.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=248 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 26	62.6 percentage of participants Interval 56.3 to 68.9	56.5 percentage of participants Interval 50.3 to 62.6	61.9 percentage of participants Interval 55.1 to 68.7	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 30	55.5 percentage of participants Interval 49.0 to 62.0	48.8 percentage of participants Interval 42.6 to 55.0	57.9 percentage of participants Interval 51.0 to 64.8	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 34	61.7 percentage of participants Interval 55.3 to 68.0	55.6 percentage of participants Interval 49.5 to 61.8	61.4 percentage of participants Interval 54.6 to 68.2	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 38	52.0 percentage of participants Interval 45.5 to 58.5	47.6 percentage of participants Interval 41.4 to 53.8	57.9 percentage of participants Interval 51.0 to 64.8	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 42	54.6 percentage of participants Interval 48.1 to 61.1	53.6 percentage of participants Interval 47.4 to 59.8	59.4 percentage of participants Interval 52.5 to 66.2	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 46	51.1 percentage of participants Interval 44.6 to 57.6	48.0 percentage of participants Interval 41.8 to 54.2	51.3 percentage of participants Interval 44.3 to 58.2	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 50	54.2 percentage of participants Interval 47.7 to 60.7	50.0 percentage of participants Interval 43.8 to 56.2	59.9 percentage of participants Interval 53.1 to 66.7	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 54	52.4 percentage of participants Interval 45.9 to 58.9	47.2 percentage of participants Interval 41.0 to 53.4	49.2 percentage of participants Interval 42.3 to 56.2	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 58	52.4 percentage of participants Interval 45.9 to 58.9	46.4 percentage of participants Interval 40.2 to 52.6	56.9 percentage of participants Interval 49.9 to 63.8	—
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Week 62	52.0 percentage of participants Interval 45.5 to 58.5	46.4 percentage of participants Interval 40.2 to 52.6	55.3 percentage of participants Interval 48.4 to 62.3	—

SECONDARY outcome

Timeframe: At Weeks 2, 6, 14, 18, and 22

Population: The FAS population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. LOCF method was used to carry forward any of the individually missing component values, and from that mix of actual and carried-forward values, the ACR responder status was determined.

ACR20-ESR was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 20% improvement from baseline in the tender/painful joint count. ii) A 20% improvement from baseline in the swollen joint count. iii) A 20% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3 with lower scores meaning less disability, e) erythrocyte sedimentation rate (ESR).

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 2	29.1 percentage of participants Interval 23.2 to 35.0	31.8 percentage of participants Interval 27.5 to 36.2	—	—
Stage 1: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 6	46.7 percentage of participants Interval 40.2 to 53.2	54.3 percentage of participants Interval 49.6 to 58.9	—	—
Stage 1: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 14	56.8 percentage of participants Interval 50.4 to 63.3	52.2 percentage of participants Interval 47.6 to 56.9	—	—
Stage 1: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 18	62.6 percentage of participants Interval 56.3 to 68.9	62.3 percentage of participants Interval 57.8 to 66.8	—	—
Stage 1: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 22	55.9 percentage of participants Interval 49.5 to 62.4	56.3 percentage of participants Interval 51.7 to 60.9	—	—

SECONDARY outcome

Timeframe: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

ACR20-ESR was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 20% improvement from baseline in the tender/painful joint count. ii) A 20% improvement from baseline in the swollen joint count. iii) A 20% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3 with lower scores meaning less disability, e) (ESR.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=248 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 26	60.8 percentage of participants Interval 54.4 to 67.1	55.6 percentage of participants Interval 49.5 to 61.8	62.4 percentage of participants Interval 55.7 to 69.2	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 30	58.1 percentage of participants Interval 51.7 to 64.6	50.0 percentage of participants Interval 43.8 to 56.2	57.4 percentage of participants Interval 50.5 to 64.3	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 34	62.1 percentage of participants Interval 55.8 to 68.4	56.9 percentage of participants Interval 50.7 to 63.0	61.4 percentage of participants Interval 54.6 to 68.2	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 38	56.4 percentage of participants Interval 49.9 to 62.8	48.8 percentage of participants Interval 42.6 to 55.0	59.4 percentage of participants Interval 52.5 to 66.2	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 42	57.3 percentage of participants Interval 50.8 to 63.7	54.4 percentage of participants Interval 48.2 to 60.6	60.9 percentage of participants Interval 54.1 to 67.7	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 46	53.7 percentage of participants Interval 47.3 to 60.2	50.0 percentage of participants Interval 43.8 to 56.2	54.3 percentage of participants Interval 47.4 to 61.3	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 50	56.4 percentage of participants Interval 49.9 to 62.8	50.8 percentage of participants Interval 44.6 to 57.0	59.4 percentage of participants Interval 52.5 to 66.2	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 54	54.6 percentage of participants Interval 48.1 to 61.1	47.2 percentage of participants Interval 41.0 to 53.4	50.8 percentage of participants Interval 43.8 to 57.7	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 58	54.2 percentage of participants Interval 47.7 to 60.7	48.8 percentage of participants Interval 42.6 to 55.0	55.8 percentage of participants Interval 48.9 to 62.8	—
Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) At Week 62	52.4 percentage of participants Interval 45.9 to 58.9	47.2 percentage of participants Interval 41.0 to 53.4	54.3 percentage of participants Interval 47.4 to 61.3	—

SECONDARY outcome

Timeframe: At Weeks 2, 6, 14, 18, and 22

Population: The FAS population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. LOCF method was used to carry forward any of the individually missing component values, and from that mix of actual and carried-forward values, the ACR responder status was determined.

ACR50 was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 50% improvement from baseline in the tender/painful joint count. ii) A 50% improvement from baseline in the swollen joint count. iii) A 50% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3, with lower scores meaning less disability, e) CRP.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 2	8.4 percentage of participants Interval 4.8 to 12.0	8.3 percentage of participants Interval 5.7 to 10.9	—	—
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 6	16.3 percentage of participants Interval 11.5 to 21.1	19.1 percentage of participants Interval 15.4 to 22.7	—	—
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 14	24.7 percentage of participants Interval 19.1 to 30.3	21.3 percentage of participants Interval 17.5 to 25.1	—	—
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 18	32.2 percentage of participants Interval 26.1 to 38.2	30.9 percentage of participants Interval 26.7 to 35.2	—	—
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 22	27.8 percentage of participants Interval 21.9 to 33.6	25.6 percentage of participants Interval 21.5 to 29.6	—	—

SECONDARY outcome

Timeframe: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

Population: Full Analysis Set population included participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR50 efficacy assessment. Overall Number of Participants indicates the number of patients with FAS. The patient number of FAS is the number of patients evaluated at baseline, which is different from number of patients who started Stage 2 or 3. ACR 50 (CRP) response rate/visit was calculated based on the number of patients achieving ACR50 criteria divided by FAS number.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=248 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=446 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 26	34.4 percentage of participants Interval 28.2 to 40.5	32.3 percentage of participants Interval 26.4 to 38.1	31.0 percentage of participants Interval 24.5 to 37.4	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 30	30.0 percentage of participants Interval 24.0 to 35.9	28.6 percentage of participants Interval 23.0 to 34.3	29.4 percentage of participants Interval 23.1 to 35.8	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 34	35.2 percentage of participants Interval 29.0 to 41.5	34.3 percentage of participants Interval 28.4 to 40.2	39.1 percentage of participants Interval 32.3 to 45.9	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 38	31.3 percentage of participants Interval 25.2 to 37.3	30.2 percentage of participants Interval 24.5 to 36.0	34.0 percentage of participants Interval 27.4 to 40.6	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 42	33.5 percentage of participants Interval 27.3 to 39.6	36.7 percentage of participants Interval 30.7 to 42.7	40.6 percentage of participants Interval 33.8 to 47.5	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 46	30.8 percentage of participants Interval 24.8 to 36.8	31.5 percentage of participants Interval 25.7 to 37.2	30.5 percentage of participants Interval 24.0 to 36.9	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 50	37.0 percentage of participants Interval 30.7 to 43.3	34.7 percentage of participants Interval 28.8 to 40.6	35.5 percentage of participants Interval 28.8 to 42.2	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 54	36.6 percentage of participants Interval 30.3 to 42.8	28.6 percentage of participants Interval 23.0 to 34.3	32.5 percentage of participants Interval 25.9 to 39.0	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 58	32.6 percentage of participants Interval 26.5 to 38.7	32.7 percentage of participants Interval 26.8 to 38.5	34.0 percentage of participants Interval 27.4 to 40.6	—
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Week 62	30.8 percentage of participants Interval 24.8 to 36.8	32.7 percentage of participants Interval 26.8 to 38.5	28.4 percentage of participants Interval 22.1 to 34.7	—

SECONDARY outcome

Timeframe: At Weeks 2, 6, 14, 18, and 22

Population: The FAS population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. LOCF method was used to carry forward any of the individually missing component values, and from that mix of actual and carried-forward values, the ACR responder status was determined.

ACR50-ESR was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 50% improvement from baseline in the tender/painful joint count. ii) A 50% improvement from baseline in the swollen joint count. iii) A 50% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3, with lower scores meaning less disability, e) ESR.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 2	6.6 percentage of participants Interval 3.4 to 9.8	6.7 percentage of participants Interval 4.4 to 9.1	—	—
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 6	14.5 percentage of participants Interval 10.0 to 19.1	17.9 percentage of participants Interval 14.4 to 21.5	—	—
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 14	23.3 percentage of participants Interval 17.8 to 28.9	21.7 percentage of participants Interval 17.9 to 25.6	—	—
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 18	31.7 percentage of participants Interval 25.7 to 37.8	29.6 percentage of participants Interval 25.4 to 33.8	—	—
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 22	27.8 percentage of participants Interval 21.9 to 33.6	26.7 percentage of participants Interval 22.6 to 30.8	—	—

SECONDARY outcome

Timeframe: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=248 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 26	33.0 percentage of participants Interval 26.9 to 39.2	31.9 percentage of participants Interval 26.1 to 37.7	30.5 percentage of participants Interval 24.0 to 36.9	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 30	29.1 percentage of participants Interval 23.2 to 35.0	28.2 percentage of participants Interval 22.6 to 33.8	28.4 percentage of participants Interval 22.1 to 34.7	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 34	35.2 percentage of participants Interval 29.0 to 41.5	34.7 percentage of participants Interval 28.8 to 40.6	39.1 percentage of participants Interval 32.3 to 45.9	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 38	32.2 percentage of participants Interval 26.1 to 38.2	30.6 percentage of participants Interval 24.9 to 36.4	32.5 percentage of participants Interval 25.9 to 39.0	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 42	33.5 percentage of participants Interval 27.3 to 39.6	36.7 percentage of participants Interval 30.7 to 42.7	37.1 percentage of participants Interval 30.3 to 43.8	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 46	29.5 percentage of participants Interval 23.6 to 35.4	31.5 percentage of participants Interval 25.7 to 37.2	29.4 percentage of participants Interval 23.1 to 35.8	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 50	34.8 percentage of participants Interval 28.6 to 41.0	34.3 percentage of participants Interval 28.4 to 40.2	34.5 percentage of participants Interval 27.9 to 41.2	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 54	36.1 percentage of participants Interval 29.9 to 42.4	28.6 percentage of participants Interval 23.0 to 34.3	29.4 percentage of participants Interval 23.1 to 35.8	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 58	32.6 percentage of participants Interval 26.5 to 38.7	32.3 percentage of participants Interval 26.4 to 38.1	33.5 percentage of participants Interval 26.9 to 40.1	—
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Week 62	29.1 percentage of participants Interval 23.2 to 35.0	32.7 percentage of participants Interval 26.8 to 38.5	27.9 percentage of participants Interval 21.7 to 34.2	—

SECONDARY outcome

Timeframe: At Weeks 2, 6, 14, 18, and 22

Population: The FAS population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. LOCF method was used to carry forward any of the individually missing component values, and from that mix of actual and carried-forward values, the ACR responder status was determined.

ACR70 was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 50% improvement from baseline in the tender/painful joint count. ii) A 70% improvement from baseline in the swollen joint count. iii) A 70% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3, with lower scores meaning less disability, e) CRP.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 2	0.9 percentage of participants Interval 0.0 to 2.1	1.3 percentage of participants Interval 0.3 to 2.4	—	—
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 6	6.6 percentage of participants Interval 3.4 to 9.8	7.2 percentage of participants Interval 4.8 to 9.6	—	—
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 14	11.0 percentage of participants Interval 6.9 to 15.1	7.8 percentage of participants Interval 5.4 to 10.3	—	—
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 18	15.0 percentage of participants Interval 10.3 to 19.6	11.7 percentage of participants Interval 8.7 to 14.6	—	—
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 22	10.6 percentage of participants Interval 6.6 to 14.6	12.1 percentage of participants Interval 9.1 to 15.1	—	—

SECONDARY outcome

Timeframe: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

Population: Full Analysis Set population included participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR70 efficacy assessment. Overall Number of Participants indicates the number of patients with FAS. The patient number of FAS is the number of patients evaluated at baseline, which is different from number of patients who started Stage 2 or 3. ACR 70 (CRP) response rate/visit was calculated based on the number of patients achieving ACR70 criteria divided by FAS number.

ACR70 was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 50% improvement from baseline in the tender/painful joint count. ii) A 70% improvement from baseline in the swollen joint count. iii) A 70% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity VAS) (0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3, with lower scores meaning less disability, e) CRP.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=248 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 46	15.0 percentage of participants Interval 10.3 to 19.6	18.5 percentage of participants Interval 13.7 to 23.4	14.7 percentage of participants Interval 9.8 to 19.7	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 38	17.6 percentage of participants Interval 12.7 to 22.6	15.7 percentage of participants Interval 11.2 to 20.3	14.7 percentage of participants Interval 9.8 to 19.7	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 42	17.2 percentage of participants Interval 12.3 to 22.1	18.5 percentage of participants Interval 13.7 to 23.4	18.3 percentage of participants Interval 12.9 to 23.7	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 50	22.0 percentage of participants Interval 16.6 to 27.4	23.0 percentage of participants Interval 17.7 to 28.2	18.3 percentage of participants Interval 12.9 to 23.7	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 26	16.3 percentage of participants Interval 11.5 to 21.1	14.5 percentage of participants Interval 10.1 to 18.9	13.2 percentage of participants Interval 8.5 to 17.9	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 30	16.3 percentage of participants Interval 11.5 to 21.1	15.3 percentage of participants Interval 10.8 to 19.8	13.2 percentage of participants Interval 8.5 to 17.9	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 34	18.1 percentage of participants Interval 13.1 to 23.1	18.1 percentage of participants Interval 13.3 to 22.9	20.8 percentage of participants Interval 15.1 to 26.5	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 54	18.1 percentage of participants Interval 13.1 to 23.1	14.9 percentage of participants Interval 10.5 to 19.4	15.7 percentage of participants Interval 10.7 to 20.8	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 58	18.9 percentage of participants Interval 13.8 to 24.0	19.8 percentage of participants Interval 14.8 to 24.7	16.2 percentage of participants Interval 11.1 to 21.4	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Week 62	17.2 percentage of participants Interval 12.3 to 22.1	18.5 percentage of participants Interval 13.7 to 23.4	13.2 percentage of participants Interval 8.5 to 17.9	—

SECONDARY outcome

Timeframe: At Weeks 2, 6, 14, 18, 22

Population: The FAS population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline ACR20 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. LOCF method was used to carry forward any of the individually missing component values, and from that mix of actual and carried-forward values, the ACR responder status was determined.

ACR70-ESR was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 50% improvement from baseline in the tender/painful joint count. ii) A 70% improvement from baseline in the swollen joint count. iii) A 70% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS)(0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3, with lower scores meaning less disability, e) ESR.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 2	0.9 percentage of participants Interval 0.0 to 2.1	1.1 percentage of participants Interval 0.1 to 2.1	—	—
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 6	5.7 percentage of participants Interval 2.7 to 8.7	6.1 percentage of participants Interval 3.8 to 8.3	—	—
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 14	9.7 percentage of participants Interval 5.8 to 13.5	7.4 percentage of participants Interval 5.0 to 9.8	—	—
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 18	14.5 percentage of participants Interval 10.0 to 19.1	11.0 percentage of participants Interval 8.1 to 13.9	—	—
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 22	11.0 percentage of participants Interval 6.9 to 15.1	11.2 percentage of participants Interval 8.3 to 14.1	—	—

SECONDARY outcome

Timeframe: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

ACR70-ESR was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 50% improvement from baseline in the tender/painful joint count. ii) A 70% improvement from baseline in the swollen joint count. iii) A 70% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), c) Participant pain assessment (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), d) HAQ-DI, total score ranged from 0-3, with lower scores meaning less disability, e) ESR.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=248 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 54	17.2 percentage of participants Interval 12.3 to 22.1	13.3 percentage of participants Interval 9.1 to 17.5	13.7 percentage of participants Interval 8.9 to 18.5	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 62	16.3 percentage of participants Interval 11.5 to 21.1	18.1 percentage of participants Interval 13.3 to 22.9	15.2 percentage of participants Interval 10.2 to 20.2	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 50	20.7 percentage of participants Interval 15.4 to 26.0	22.6 percentage of participants Interval 17.4 to 27.8	15.7 percentage of participants Interval 10.7 to 20.8	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 26	15.4 percentage of participants Interval 10.7 to 20.1	15.3 percentage of participants Interval 10.8 to 19.8	12.7 percentage of participants Interval 8.0 to 17.3	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 30	15.4 percentage of participants Interval 10.7 to 20.1	14.1 percentage of participants Interval 9.8 to 18.4	11.7 percentage of participants Interval 7.2 to 16.2	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 34	16.7 percentage of participants Interval 11.9 to 21.6	16.9 percentage of participants Interval 12.3 to 21.6	19.3 percentage of participants Interval 13.8 to 24.8	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 38	16.3 percentage of participants Interval 11.5 to 21.1	16.1 percentage of participants Interval 11.6 to 20.7	14.2 percentage of participants Interval 9.3 to 19.1	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 42	14.5 percentage of participants Interval 10.0 to 19.1	17.3 percentage of participants Interval 12.6 to 22.1	15.7 percentage of participants Interval 10.7 to 20.8	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 58	17.2 percentage of participants Interval 12.3 to 22.1	18.1 percentage of participants Interval 13.3 to 22.9	14.7 percentage of participants Interval 9.8 to 19.7	—
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Week 46	15.4 percentage of participants Interval 10.7 to 20.1	16.9 percentage of participants Interval 12.3 to 21.6	13.2 percentage of participants Interval 8.5 to 17.9	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 6, 14, 18, and 22

The HAQ-DI score was defined as the average of the scores of eight functional categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities), usually completed by the participant. Responses in each functional category are collected as 0 (without any difficulty) to 3 (unable to do a task in that area), with or without aids or devices. The eight category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled), where lower scores indicated less disability. Negative change from baseline indicates improvement (less disability).

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22 Baseline	1.32 score on a scale Standard Deviation 0.55	1.34 score on a scale Standard Deviation 0.58	—	—
Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22 Change at Week 2	-0.21 score on a scale Standard Deviation 0.42	-0.28 score on a scale Standard Deviation 0.45	—	—
Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22 Change at Week 14	-0.35 score on a scale Standard Deviation 0.55	-0.35 score on a scale Standard Deviation 0.54	—	—
Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22 Change at Week 18	-0.41 score on a scale Standard Deviation 0.53	-0.43 score on a scale Standard Deviation 0.58	—	—
Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22 Change at Week 6	-0.33 score on a scale Standard Deviation 0.50	-0.37 score on a scale Standard Deviation 0.53	—	—
Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22 Change at Week 22	-0.35 score on a scale Standard Deviation 0.59	-0.39 score on a scale Standard Deviation 0.59	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=249 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 26	-0.40 score on a scale Standard Deviation 0.59	-0.44 score on a scale Standard Deviation 0.63	-0.40 score on a scale Standard Deviation 0.58	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 30	-0.40 score on a scale Standard Deviation 0.57	-0.46 score on a scale Standard Deviation 0.62	-0.38 score on a scale Standard Deviation 0.59	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 38	-0.43 score on a scale Standard Deviation 0.59	-0.46 score on a scale Standard Deviation 0.61	-0.41 score on a scale Standard Deviation 0.63	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 42	-0.48 score on a scale Standard Deviation 0.56	-0.52 score on a scale Standard Deviation 0.65	-0.46 score on a scale Standard Deviation 0.62	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 46	-0.48 score on a scale Standard Deviation 0.60	-0.51 score on a scale Standard Deviation 0.67	-0.43 score on a scale Standard Deviation 0.60	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 34	-0.47 score on a scale Standard Deviation 0.58	-0.50 score on a scale Standard Deviation 0.61	-0.44 score on a scale Standard Deviation 0.58	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 50	-0.49 score on a scale Standard Deviation 0.58	-0.55 score on a scale Standard Deviation 0.64	-0.47 score on a scale Standard Deviation 0.61	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 54	-0.49 score on a scale Standard Deviation 0.58	-0.49 score on a scale Standard Deviation 0.64	-0.39 score on a scale Standard Deviation 0.63	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 58	-0.49 score on a scale Standard Deviation 0.59	-0.52 score on a scale Standard Deviation 0.64	-0.44 score on a scale Standard Deviation 0.60	—
Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 62	-0.47 score on a scale Standard Deviation 0.59	-0.51 score on a scale Standard Deviation 0.64	-0.42 score on a scale Standard Deviation 0.61	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 6, 14, 18, and 22

Disease activity was assessed using RAPID3, based on participant-reported multi-dimensional health assessment questionnaire (MDHAQ). RAPID3 included 3 core data set measures of physical function, pain, and participant global estimate.Physical function=mean of scores from 10 individual questions on activities of daily living (each question scored from '0'=no difficulty to '3'=much difficulty), scores were transformed to give total score=0-10, higher scores=greater difficulty.Pain and global estimate of health measured on Likert scale from '0'=no pain to '10'=pain as bad as it could be. RAPID3 composite score: mean of physical function, pain, and global assessment scores, ranging from 0 to 10, higher values=greater disease activity. Total score range of RAPID3 score was 0=no difficulty; 30=greater difficultly, and disease activity categories were as follows: remission: 0-3, low: \>3.1 to 6, moderate: \>6.1-12, and high: \>12.1. Negative change from baseline indicates less disease activity.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22 Baseline	17.03 score on a scale Standard Deviation 4.76	17.37 score on a scale Standard Deviation 4.76	—	—
Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22 Change at Week 2	-2.99 score on a scale Standard Deviation 4.42	-3.79 score on a scale Standard Deviation 4.89	—	—
Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22 Change at Week 6	-4.15 score on a scale Standard Deviation 5.14	-5.05 score on a scale Standard Deviation 5.62	—	—
Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22 Change at Week 14	-5.04 score on a scale Standard Deviation 5.80	-4.91 score on a scale Standard Deviation 6.47	—	—
Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22 Change at Week 18	-5.99 score on a scale Standard Deviation 5.96	-5.73 score on a scale Standard Deviation 6.51	—	—
Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22 Change at Week 22	-4.71 score on a scale Standard Deviation 6.42	-5.41 score on a scale Standard Deviation 6.54	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62

Population: The FAS population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline RAPID3 efficacy assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable at specific time point.

Disease activity was assessed using RAPID3, based on participant-reported multi-dimensional health assessment questionnaire (MDHAQ). RAPID3 included 3 core data set measures of physical function, pain and participant global estimate. Physical function=mean of scores from 10 individual questions on activities of daily living (each question scored from '0'=no difficulty to '3'=much difficulty), scores were transformed to give total score=0-10, higher scores=greater difficulty. Pain and global estimate of health measured on Likert scale from '0'=no pain to '10'=pain as bad as it could be. RAPID3 composite score: mean of physical function, pain, and global assessment scores, ranging from 0 to 10, higher values=greater disease activity. Total score range of RAPID3 score was 0=no difficulty-30=greater difficultly, and disease activity categories were as follows: remission: 0-3, low: \>3.1 to 6, moderate: \>6.1-12, and high: \>12.1. Negative change from baseline indicates less disease activity.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=249 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 26	-5.81 score on a scale Standard Deviation 6.23	-6.34 score on a scale Standard Deviation 6.55	-5.64 score on a scale Standard Deviation 6.43	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 30	-5.43 score on a scale Standard Deviation 6.38	-6.41 score on a scale Standard Deviation 6.81	-5.26 score on a scale Standard Deviation 6.67	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 34	-6.24 score on a scale Standard Deviation 6.06	-7.39 score on a scale Standard Deviation 6.51	-6.22 score on a scale Standard Deviation 6.75	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 38	-5.91 score on a scale Standard Deviation 6.25	-6.59 score on a scale Standard Deviation 7.14	-5.86 score on a scale Standard Deviation 6.94	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 42	-6.69 score on a scale Standard Deviation 6.10	-7.40 score on a scale Standard Deviation 6.82	-6.49 score on a scale Standard Deviation 6.49	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 46	-6.34 score on a scale Standard Deviation 6.35	-7.11 score on a scale Standard Deviation 6.99	-5.79 score on a scale Standard Deviation 6.53	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 50	-6.85 score on a scale Standard Deviation 6.36	-7.94 score on a scale Standard Deviation 7.22	-6.48 score on a scale Standard Deviation 6.63	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 54	-6.63 score on a scale Standard Deviation 6.33	-7.11 score on a scale Standard Deviation 7.27	-5.38 score on a scale Standard Deviation 6.64	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 58	-6.84 score on a scale Standard Deviation 6.54	-7.83 score on a scale Standard Deviation 7.05	-6.41 score on a scale Standard Deviation 6.25	—
Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 Change at Week 62	-5.35 score on a scale Standard Deviation 6.83	-6.28 score on a scale Standard Deviation 7.46	-5.74 score on a scale Standard Deviation 6.67	—

SECONDARY outcome

Timeframe: Baseline, Weeks 14 and 22

Population: The ITT population included all participants who were randomized. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable at specific time point.

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental heallth) with a Subscale Total score for each scaled from 0 (minimum) to 100 (maximum) with a Total Overall score on a 0-800 scale, with higher scores indicating better health. where higher score indicates highest level of functioning. These 8 aspects can also be summarized as Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life). A positive change indicates improvement while a negative change indicates worsening of health status and quality of life. Change from baseline in overall total score for SF-36 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 14 and 22 Baseline	360.46 score on a scale Standard Deviation 116.64	358.20 score on a scale Standard Deviation 126.93	—	—
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 14 and 22 Change at Week 14	79.90 score on a scale Standard Deviation 124.86	77.59 score on a scale Standard Deviation 124.72	—	—
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 14 and 22 Change at Week 22	90.02 score on a scale Standard Deviation 122.36	82.94 score on a scale Standard Deviation 129.28	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 38 and 62

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental heallth) with a Subscale Total score for each scaled from 0 (minimum) to 100 (maximum) with a Total Overall score on a 0-800 scale, with higher scores indicating better health. where higher score indicates highest level of functioning. Total score for each subscale scaled from 0 (minimum) to 100 (maximum), where higher score indicates highest level of functioning. These 8 aspects can also be summarized as PCS with score range 0-100 (higher score-better quality of life) and a MCS with score range 0-100 (higher score-better quality of life). A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=249 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 38 and 62 Change at Week 38	95.10 score on a scale Standard Deviation 127.26	96.93 score on a scale Standard Deviation 136.80	87.61 score on a scale Standard Deviation 129.67	—
Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 38 and 62 Change at Week 62	81.56 score on a scale Standard Deviation 143.91	95.24 score on a scale Standard Deviation 148.23	87.51 score on a scale Standard Deviation 122.36	—

SECONDARY outcome

Timeframe: Baseline, Weeks 14 and 22

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. A Subscale Total score for each scaled from 0 (minimum) to 100 (maximum). Total score for each subscale scaled from 0 (minimum) to 100 (maximum), where higher score indicates highest level of functioning. These 2 subscale aspects can also be summarized as PCS with score range 0-100 (higher score-better quality of life) and a MCS with score range 0-100 (higher score-better quality of life). A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=446 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 14 and 22 Change at Week 14 (Mental Component)	3.05 score on a scale Standard Deviation 10.36	2.56 score on a scale Standard Deviation 10.38	—	—
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 14 and 22 Change at Week 22 (Mental Component)	4.05 score on a scale Standard Deviation 9.48	2.71 score on a scale Standard Deviation 10.83	—	—
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 14 and 22 Baseline (Physical Component)	30.22 score on a scale Standard Deviation 7.72	30.53 score on a scale Standard Deviation 7.24	—	—
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 14 and 22 Change at Week 14 (Physical Component)	5.42 score on a scale Standard Deviation 7.86	5.64 score on a scale Standard Deviation 8.82	—	—
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 14 and 22 Change at Week 22 (Physical Component)	5.61 score on a scale Standard Deviation 8.36	6.03 score on a scale Standard Deviation 8.79	—	—
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 14 and 22 Baseline (Mental Component)	43.59 score on a scale Standard Deviation 11.57	43.02 score on a scale Standard Deviation 12.45	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 38 and 62

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=249 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 38 and 62 Change at Week 38 (Physical Component)	6.94 score on a scale Standard Deviation 8.37	6.86 score on a scale Standard Deviation 9.31	6.22 score on a scale Standard Deviation 9.62	—
Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 38 and 62 Change at Week 62 (Physical Component)	6.14 score on a scale Standard Deviation 8.79	6.23 score on a scale Standard Deviation 9.78	6.11 score on a scale Standard Deviation 8.60	—
Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 38 and 62 Change at Week 38 (Mental Component)	3.09 score on a scale Standard Deviation 10.55	3.38 score on a scale Standard Deviation 11.32	3.10 score on a scale Standard Deviation 10.58	—
Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 38 and 62 Change at Week 62 (Mental Component)	2.45 score on a scale Standard Deviation 10.92	3.93 score on a scale Standard Deviation 11.59	3.16 score on a scale Standard Deviation 10.29	—

SECONDARY outcome

Timeframe: Week 46: Pre-dose, 1 hour after infusion, at end of infusion, at 4 hours and 24 hours after infusion and at Week 47, Week 48, Week 50, Week 52, and Week 54 post-dose

Drug concentrations in blood were evaluated from week 46 to week 54 after the initial administration date. Blood sampling was performed before administration of week 46, at the end of the infusion, and at 4 hours, 24 hours, 7 days (week 47), 14 days (week 48), 28 days (week 50), and 56 days (before administration of week 54). Cmin was define as the lowest drug concentration among all blood sampling points for an individual patient.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=159 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=155 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=146 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Minimum Observed Serum Concentration (Cmin) of NI-071 and Remicade US	839.1 ng/mL Standard Deviation 1322.2	754.1 ng/mL Standard Deviation 1380.0	762.6 ng/mL Standard Deviation 1207.2	—

SECONDARY outcome

Timeframe: Week 46: Pre-dose, 1 hour after infusion, at end of infusion, at 4 hours and 24 hours after infusion and at Week 47, Week 48, Week 50, Week 52, and Week 54 post-dose

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=159 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=155 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=146 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Time to Reach the Maximum Serum Concentration (Tmax) of NI-071 and Remicade US	52.37 hours Standard Deviation 243.64	41.57 hours Standard Deviation 217.28	32.98 hours Standard Deviation 191.02	—

SECONDARY outcome

Timeframe: Baseline up to Week 62

Population: The safety population included participants who received at least 1 dose of study drug.

An adverse event (AE) was defined as any untoward medical condition that occurs in participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment. A TEAE was defined as an adverse event with a start date on or after the first dose of Investigational product (IP), or a start date before the date of the first dose of IP but increased in severity on or after the date of the first dose of IP. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Number of participants with TEAEs and Serious TEAEs were reported.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=451 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=254 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with Serious TEAEs	19 Participants	41 Participants	28 Participants	13 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	157 Participants	330 Participants	181 Participants	149 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 62

Population: The safety population included participants who received at least 1 dose of study drug.

A TEAE was defined as an adverse event with a start date on or after the first dose of IP or a start date before the date of the first dose of IP but increased in severity on or after the date of the first dose of IP.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=451 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=254 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Number of Participants With TEAEs of Special Interest	33 Participants	68 Participants	43 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 6, 14, and 22

Population: The safety population included participants who received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable at specific time point.

Number of Participants With Positive Serum ADA are reported.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=451 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 2	18 Participants	44 Participants	—	—
Stage 1: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) Baseline	2 Participants	15 Participants	—	—
Stage 1: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 6	59 Participants	143 Participants	—	—
Stage 1: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 14	150 Participants	303 Participants	—	—
Stage 1: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 22	187 Participants	337 Participants	—	—

SECONDARY outcome

Timeframe: At Weeks 30, 38, 46, 54, and 62

Number of Participants With Positive Serum Anti-drug Antibodies (ADA) are reported.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=254 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 30	185 Participants	166 Participants	164 Participants	—
Stage 2 and 3: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 38	167 Participants	162 Participants	146 Participants	—
Stage 2 and 3: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 46	153 Participants	150 Participants	141 Participants	—
Stage 2 and 3: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 54	147 Participants	145 Participants	141 Participants	—
Stage 2 and 3: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Week 62	187 Participants	191 Participants	165 Participants	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 6, 14, and 22

Number of Participants with Positive Serum neutralizing Antibodies were reported.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=451 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 1: Number of Participants With Positive Serum Neutralizing Antibodies Baseline	1 Participants	7 Participants	—	—
Stage 1: Number of Participants With Positive Serum Neutralizing Antibodies At Week 2	1 Participants	10 Participants	—	—
Stage 1: Number of Participants With Positive Serum Neutralizing Antibodies At Week 6	11 Participants	34 Participants	—	—
Stage 1: Number of Participants With Positive Serum Neutralizing Antibodies At Week 14	53 Participants	122 Participants	—	—
Stage 1: Number of Participants With Positive Serum Neutralizing Antibodies At Week 22	80 Participants	143 Participants	—	—

SECONDARY outcome

Timeframe: At Weeks 30, 38, 46, 54, and 62

Population: The safety population included participants who received at least 1 dose of study drug. Here, "Number Analyzed" signifies those participants who were evaluable at specific time point. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Number of Participants with Positive Serum neutralizing Antibodies were reported.

Outcome measures

Outcome measures
Measure	Stage 1: NI-071 Group n=227 Participants Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 1: Remicade-US Group n=254 Participants Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Switch Group n=197 Participants Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group Participants who received Remicade US during stage 1 and were re-randomized during stage 2 received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Stage 2 and 3: Number of Participants With Positive Serum Neutralizing Antibodies At Week 46	78 Participants	87 Participants	75 Participants	—
Stage 2 and 3: Number of Participants With Positive Serum Neutralizing Antibodies At Week 54	77 Participants	87 Participants	75 Participants	—
Stage 2 and 3: Number of Participants With Positive Serum Neutralizing Antibodies At Week 62	114 Participants	124 Participants	97 Participants	—
Stage 2 and 3: Number of Participants With Positive Serum Neutralizing Antibodies At Week 30	92 Participants	90 Participants	78 Participants	—
Stage 2 and 3: Number of Participants With Positive Serum Neutralizing Antibodies At Week 38	94 Participants	96 Participants	69 Participants	—

Adverse Events

Stage 1, 2 and 3: NI-071 Group

Serious events: 19 serious events

Other events: 96 other events

Deaths: 1 deaths

Stage 1: Remicade-US Group

Serious events: 41 serious events

Other events: 174 other events

Deaths: 1 deaths

Stage 2 and Stage 3: Remicade US to Remicade-US Group

Serious events: 28 serious events

Other events: 80 other events

Deaths: 0 deaths

Stage 2 and Stage 3: Remicade US to Switch Group

Serious events: 13 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Stage 1, 2 and 3: NI-071 Group n=227 participants at risk Participants received IV infusion of NI-071 at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1 and at Weeks 22, 30, 38, 46, and 54 during stage 2. Participants were followed up to Week 62 (Stage 3).	Stage 1: Remicade-US Group n=451 participants at risk Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.	Stage 2 and Stage 3: Remicade US to Remicade-US Group n=254 participants at risk Participants who received Remicade US during stage 1; were re-randomized during stage 2 to continue Remicade-US dose 3 mg/kg from Week 22 through Week 54 with every 8 weeks dosing intervals. Participants were followed up to Week 62 (Stage 3).	Stage 2 and Stage 3: Remicade US to Switch Group n=197 participants at risk Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).
Infections and infestations Bronchitis	5.7% 13/227 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	3.5% 16/451 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	3.9% 10/254 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	3.0% 6/197 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.
Infections and infestations Nasopharyngitis	12.3% 28/227 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	9.5% 43/451 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	8.7% 22/254 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	10.7% 21/197 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.
Infections and infestations Upper Respiratory Tract Infection	10.6% 24/227 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	9.1% 41/451 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	8.3% 21/254 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	10.2% 20/197 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.
Nervous system disorders Headache	7.0% 16/227 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	4.7% 21/451 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	3.1% 8/254 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	6.6% 13/197 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.
Musculoskeletal and connective tissue disorders Arthralgia	1.3% 3/227 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	3.5% 16/451 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	2.4% 6/254 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	5.1% 10/197 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.
Investigations Alanine Aminotransferase Increased	3.5% 8/227 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	4.7% 21/451 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	3.1% 8/254 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	6.6% 13/197 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.
Investigations Aspartate Aminotransferase Increased	1.8% 4/227 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	3.5% 16/451 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	2.0% 5/254 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.	5.6% 11/197 • Baseline up to Week 62 The safety population included participants who received at least 1 dose of study drug at Baseline. The analyses were calculated by the number of All-Cause Mortality/safety population, the number of SAE's/safety population and the number of oher AE's/safety population. The patient number of safety population is the number of patients evaluated at baseline, which is different from the number of patients who started to Stage 2 or 3.

Additional Information

Hiroshi Anekawa

Nichi-Iko Pharmaceutical Co., Ltd

Phone: +81-3-6262-1564

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place