A Study of Nipocalimab in Adults With Primary Sjogren's Syndrome (pSS)

Change from baseline in ESSPRI score at Week 24 was reported. The ESSPRI was a patient-reported assessment of the severity of dryness, fatigue, and pain associated with primary Sjögren's Syndrome. Participants were asked to rate the severity of dryness, fatigue and pain over the past 2 weeks on a numeric rating scale (NRS), ranging from 0 "no symptom" to 10 "maximal imaginable" symptoms (dryness, fatigue, pain). Each domain was scored on scale of 0 to 10 (0 = no symptom at all and 10 = worst symptom imaginable). A total score was calculated as the mean of the 3 individual domain scores, where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10, where higher ESSPRI scores indicated more severe symptoms.

ESSDAI covers 11 organ-specific domain (constitutional, lymphadenopathy and lymphoma, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological) and 1 biological domain. Activity in each domain was scored at 3 to 4 level (no/low/moderate/high) according to severity as assessed by investigator based on criteria. Activity-level score range from 0 to 3 (0=no activity, 3=high activity; not all domain have 4 activity level). Each domain was assigned weight range from 1 to 6. Activity-level score was multiplied by corresponding domain weight to get weighted domain score. Each domain had specific scoring range determined by its activity level and assigned weight. Sum of weighted domain score was overall ESSDAI score, ranging from 0 to 123 (0=no systemic disease activity, higher score indicated greater systemic disease activity). Decrease from baseline meant improvement.

In clinESSDAI, physician score systemic disease activity level on 11 organ-specific domain (constitutional, lymphadenopathy and lymphoma, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, and hematological), with each domain activity in 3 to 4 level (no/low/moderate/high) according to their severity assessed by investigator based on predefined criteria. Activity-level score range from 0 to 3 (0=no activity, 3=high activity; not all domain include 4 activity level). Each domain was assigned weight from 1 to 7; activity-level score was multiplied by corresponding domain weight to get weighted domain score. Each domain had specific scoring range determined by its activity level and assigned weight. Sum of weighted domain score was overall score ranging from 0 to 135 (lower score=no symptom, higher score=severe symptom). Decrease from baseline indicated improvement.

Percentage of participants with ESSPRI response defined as a decrease of one point or a decrease of >= 15% from baseline at Week 24 was reported. The ESSPRI was a patient-reported assessment of the severity of dryness, fatigue, and pain associated with primary Sjogren's syndrome. Participants were asked to rate the severity of dryness, fatigue and pain over the past 2 weeks on a numeric rating scale (NRS), ranging from 0 "no symptom" to 10 "maximal imaginable" symptoms (dryness, fatigue, pain). Each domain was scored on scale of 0 to 10 (0 = no symptom at all and 10 = worst symptom imaginable). A total score was calculated as the mean of the 3 individual domain scores, where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10, where higher ESSPRI scores indicated more severe symptoms.

Percentage of participants with disease response according to STAR composite score at Week 24 was reported. STAR was a composite endpoint assessing multiple clinically relevant disease features. A STAR response was defined as a composite score of >=5 points in the 5 STAR domains, with weighting in parentheses: (i) decrease of >=3 in clinESSDAI score (3), (ii) decrease of >=1 point or >=15% from baseline in ESSPRI score (3), (iii) abnormal Schirmer's test at baseline and increase of >=5 millimeter (mm)/normal Schirmer's test at baseline and no change to abnormal/abnormal ocular staining score at baseline and a decrease of >=2 points/normal ocular staining score at baseline and no change to abnormal (1), (iv) increase of >=25% in unstimulated whole saliva/any increase if score is 0 at baseline (1), (v) decrease of >=25% in rheumatoid factor/decrease of >=10% in immunoglobulin G (IgG) (1). Overall score was sum of all domain weight, which range from 0 to 9 (higher score = worse outcome).

DAL=level of disease activity severity (no/low/moderate/severe) in each clinESSDAI/ESSDAI domain. In clinESSDAI, physician score DAL on 11 organ-specific domains (constitutional, lymphadenopathy, lymphoma, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral and central nervous system, hematological) with each domain activity in 3-4 level according to severity (0=no activity, 3=high activity; not all domains have 4 activity level). Each domain given weight: 1-7, activity level score * domain weight. Sum of weighted domain score was overall score (0-135: higher score=severe symptom). A decrease from baseline indicated improvement. Participants with improvement of >= 4 points (minimal clinically important improvement) were reported in this outcome measure. ESSDAI differs from clinESSDAI by adding biological domain that cover B-cell biomarker (elevated gamma-globulin/IgG level, low complement level, cryoglobulinemia, monoclonal gammopathy).

Percentage of participants with improvement from baseline in >= 3 of 5 CRESS categories at Week 24 was reported. CRESS was a composite tool that incorporates measures of disease activity (clinESSDAI), symptoms (ESSPRI), glandular function and systemic inflammation to assess disease activity. A CRESS response was defined as a response in >= 3 of the following 5 categories: (i) clinESSDAI score less than (<) 5 (low disease activity), (ii) decrease of >= 1 point or >= 15% from baseline in ESSPRI score, (iii) abnormal Schirmer's test at baseline (<= 5 mm) and an increase of >= 5 mm, or normal Schirmer's test at baseline and no change to abnormal, (iv) increase of >= 25% in unstimulated whole saliva or any increase if score is 0 at baseline, (v) decrease of >= 25% in rheumatoid factor or decrease of >= 10% in IgG.

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.

Number of participants with AESIs were reported. AEs was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. Treatment-emergent adverse events associated with the following situations were considered AESIs. (i) Infections that were severe or require IV anti-infective or operative/invasive intervention; (ii) Hypoalbuminemia with albumin < 20 grams per liter (g/L) (< 2.0 grams per deciliter [g/dL]); applicable to participants who had albumin greater than (>) 20 g/L at previous assessments. Those who entered with < 20 g/L and stayed below this level were not reported as an AESI. Those who entered with an albumin > 20 g/L or those who entered with albumin < 20g/L and then had an increase in albumin > 20 g/L which subsequently decreased to < 20 g/L were reported as an AESI.

A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly or any situation deemed medically important by the investigator. Treatment-emergent SAEs were defined as SAEs with onset or worsening on or after date of first dose of study treatment.

Number of participants with TEAEs leading to treatment discontinuation were reported. AEs was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.

Number of participants with clinically significant abnormalities in vital signs were reported. Vital signs parameters including temperature (< 36 degree Celsius and > 38 degree Celsius), pulse rate (<= 50 beats per minute [bpm] and with >= 15 bpm decrease from baseline and >= 120 bpm and with >= 15 bpm increase from baseline), and blood pressure (systolic blood pressure [SBP]: <= 90 millimeters of mercury [mmHg] and with >= 20 mmHg decrease from baseline and >= 160 mmHg and with >= 20 mmHg increase from baseline; diastolic blood pressure [DBP]: <= 50 mmHg and with >= 15 mmHg decrease from baseline and >= 100 mmHg and with >= 15 mmHg increase from baseline). Only those categories in which at least 1 participant had data were reported.

Laboratory parameters included hematology (platelet count [platelets: decrease > 20% and value < 100)], red blood cell count, hemoglobin, hematocrit, white blood cell count with differential [lymphocytes: decrease > 20% and value < 0.08], [leukocytes: decrease > 10% and value < 2.5], [neutrophils: increase > 30% and value > 0.90], [eosinophils: increase > 20% and value > 0.10]), serum chemistry (phosphate [decrease > 10% and value < 0.6), lipid panel (high-density lipoprotein [HDL] and low-density lipoprotein [LDL], creatine kinase: increase > 20% and value > 960, cholesterol: value >= 6.2), urinalysis, and blood coagulation. Participants were assessed at Weeks 2, 4, 8, 12, 16, 20, 24, 30 but only those categories and timepoints (Weeks 2, 4, 8, 12, 16, 24, 30) in which at least 1 participant had data were reported.

Serum concentrations of nipocalimab over time was reported. This outcome measure was planned to be analyzed for specified arms only.

Change from baseline in CRP were reported.

Change from baseline in ESR were reported. ESR was a composite outcome assessment that measures the degree of inflammation.

Change from baseline in total IgG, IgG1, IgG2, IgG3, IgG4 were reported.

Change from baseline in autoantibodies included anti-Ro60/SSA, anti-La/SSB, and anti-Ro52/tripartite motif-containing protein 21 (Anti-Ro52/TRIM21) were reported.

Change from baseline in autoantibodies included RF were reported.

Number of participants with ADA to nipocalimab were reported. The presence of ADA to nipocalimab in serum was determined by a sensitive and drug-tolerant electrochemiluminescence immunoassay (ECLIA) method. This outcome measure was planned to be analyzed for specified arms only.

Number of participants with NAbs were reported. Neutralising antibodies to nipocalimab were assessed using a non-cell based competitive ligand binding ECLIA assay. This outcome measure was planned to be analyzed for specified arms only.