A Phase 3 Study of NI-071 in Participants With Rheumatoid Arthritis (RADIANCE)
- Registration Number
- NCT02990806
- Lead Sponsor
- Nichi-Iko Pharmaceutical Co., Ltd.
- Brief Summary
The purpose of this study was to demonstrate similarity of NI-071 (proposed biosimilar to infliximab) to US REMICADE® (reference product) in terms of safety and efficacy in participants with rheumatoid arthritis (RA) not adequately responding to methotrexate (MTX).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 683
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Patients with a diagnosis of rheumatoid arthritis (RA) as defined by the 2010 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) classification criteria.
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Patients have active RA, as confirmed by the following criteria:
- ≥6 swollen joints and ≥6 tender joints at screening and baseline (28-joint count).
- Either C-reactive protein (CRP) ≥0.7 mg/dL (≥7.0 mg/L) or erythrocyte sedimentation rate (ESR) ≥28 mm/h at screening.
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Patients taking methotrexate (MTX) (oral or parenteral) for at least 3 months prior to screening and at a stable dose of between 10 and 25 mg/week for at least 8 weeks. Concomitant folic/folinic acid at a dose of at least 5 mg/week is to be taken during the study; patients can start treatment with folic/folinic acid at screening if not already receiving it.
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If the patient is currently taking non-steroidal anti-inflammatory drugs (NSAIDs), the patient must be on a stable dose for at least 4 weeks prior to screening and during the study.
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Patients who are ≥18 and ≤75 years of age at screening.
- Patients who are rated as Class IV according to the 1991 ACR revised criteria for classification of global functional status for RA.
- Patients who have received disease-modifying anti rheumatic drugs (DMARDs), other than MTX, within a period prior to screening shorter than the washout period appropriate to the pharmacodynamic profile of the specific drug.
- Patients who have received immunosuppressive drugs within 4 weeks prior to screening. Patients on a stable dose of oral corticosteroids (≤10 mg/day prednisone or equivalent) for ≥4 weeks prior to screening are permitted.
- Patients who have received intra-articular, intramuscular, intravenous, or epidural injection of corticosteroids within 4 weeks prior to screening.
- Patients who have received intra-articular sodium hyaluronate injections within 4 weeks prior to screening.
- Patients who have received surgical therapy for RA such as synovectomy or arthroplasty within 6 months prior to screening.
- Patients who have received arthrocentesis within 4 weeks prior to screening.
- Patients who have had prior treatment with infliximab.
- Patients who have had prior treatment with >1 biological drug or >1 protein kinase inhibitor for RA either as part of clinical management or during a clinical study.
- Patients who have had prior treatment with tumor necrosis factor alpha (TNF-α) inhibitors for RA who had lack of efficacy as per clinical judgment (primary failure). Patients who have discontinued TNF-α inhibitors for RA (other than infliximab) for any reason other than lack of efficacy are allowed.
- Presence of chronic or acute infection at screening, including positive result for active tuberculosis (TB).
- Patients with an acute infection requiring parenteral antibiotics within 4 weeks of study dosing or requiring oral/topical antibiotics within 2 weeks of study dosing.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Stage 1: Remicade-US Group Remicade 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 Remicade 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 Remicade 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 NI-071 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). Stages 1, 2 and 3: NI-071 Group NI-071 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 (Stage 3).
- Primary Outcome Measures
Name Time Method Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR20-CRP) Response Rate at Week 22 At Week 22 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.
Stage 2 and 3: Area Under the Serum Concentration-time Curve Interval (AUCtau) of NI-071 and Remicade US 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 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.
Stage 2 and 3: Maximum Observed Serum Concentration (Cmax) of NI-071 and Remicade US 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 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.
- Secondary Outcome Measures
Name Time Method 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, Weeks 2, 6, 14, 18, and 22 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.
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 Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 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.
Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 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.
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Weeks 2, 6, 14, 18, and 22 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.
Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 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.
Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 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.
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, 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.
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 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.
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 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.
Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate At Weeks 2, 6, 14, 18, and 22 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.
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 Weeks 2, 6, 14, 18, and 22 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).
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 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.
Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR At Weeks 2, 6, 14, 18, and 22 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.
Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR 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.
Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22 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).
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 Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 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).
Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22 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.
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate At Weeks 2, 6, 14, 18, and 22 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.
Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 14 and 22 Baseline, Weeks 14 and 22 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.
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, 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.
Stage 2 and 3: Minimum Observed Serum Concentration (Cmin) of NI-071 and Remicade US 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.Stage 1: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) Baseline, Weeks 2, 6, 14, and 22 Number of Participants With Positive Serum ADA are reported.
Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR At Weeks 2, 6, 14, 18, 22 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.
Stage 2 and 3: Time to Reach the Maximum Serum Concentration (Tmax) of NI-071 and Remicade US 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 Stage 2 and 3: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) At Weeks 30, 38, 46, 54, and 62 Number of Participants With Positive Serum Anti-drug Antibodies (ADA) are reported.
Stage 2 and 3: Number of Participants With Positive Serum Neutralizing Antibodies At Weeks 30, 38, 46, 54, and 62 Number of Participants with Positive Serum neutralizing Antibodies were reported.
Number of Participants With TEAEs of Special Interest Baseline up to Week 62 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.
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 Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 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.
Stage 1: Number of Participants With Positive Serum Neutralizing Antibodies Baseline, Weeks 2, 6, 14, and 22 Number of Participants with Positive Serum neutralizing Antibodies were reported.
Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 38 and 62 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.
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 Baseline, Weeks 38 and 62 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Baseline up to Week 62 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.
Trial Locations
- Locations (1)
Nichi-Iko Investigational Site
🇬🇧Truro, United Kingdom