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

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Number of Participants With Positive Serum ADA are reported.

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

Number of Participants with Positive Serum neutralizing Antibodies were reported.

Number of Participants with Positive Serum neutralizing Antibodies were reported.