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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of nipocalimab in participants with primary Sjogren's syndrome (pSS) versus placebo.

Detailed Description
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Sjogren's syndrome is a chronic, progressive autoimmune disease of unclear etiology typically originating in exocrine glands and capable of affecting the function of almost any organ system in the body. Nipocalimab is a fully human aglycosylated immunoglobulin (Ig)G1 monoclonal antibody designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal fragment crystallizable receptor (FcRn). Nipocalimab blocks the binding site for IgG on FcRn, leads directly to increased IgG catabolism and a decrease in circulating IgG antibody concentrations, including pathogenic IgG antibody concentrations, and directly inhibits inflammatory cellular responses to these pathogenic IgG. Therefore, Nipocalimab may successfully treat pSS and improve disease manifestations. The study will consist of Screening Period (less than or equal to [<=] 6 Weeks), Double-blind Treatment Period (24 Weeks), and a Follow-up Period (6 Weeks). Key safety assessments will include adverse events (AEs), serious adverse events (SAEs), adverse events of special interests (AESIs), clinical laboratory safety tests (hematology, chemistry, urinalysis, and lipid profile) and vital signs. The total duration of the study is up to 36 weeks.

Official Title
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A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Assess the Efficacy and Safety of Nipocalimab in Adults With Primary Sjogren's Syndrome (pSS)

Conditions
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Sjogren's Syndrome

Intervention / Treatment
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* Other: Placebo
* Drug: Nipocalimab
* Drug: Standard of Care Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets classification criteria for primary Sjogren's syndrome (pSS) by the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) at the time of screening, and was diagnosed with pSS no less than 26 weeks prior to screening At screening is seropositive for antibodies to pSS-associated antigen A (Ro/Sjogren's syndrome-related antigen A [SSA]) Total Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) score greater than or equal to (>=) 6 At least one abnormal laboratory marker of pSS-related inflammatory disease activity, and at least low activity in one or more specified European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) domains It is recommended that participants are up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines. For study participants who received locally-approved (and including emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccines recently prior to study entry, applicable local vaccine labelling, guidelines, and standards-of-care for participants receiving immune-targeted therapy will be followed when determining an appropriate interval between vaccination and study enrollment Exclusion Criteria: Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her pSS or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant Comorbidities (for example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months Has any unstable or progressive manifestation of pSS that is likely to warrant escalation in therapy beyond permitted background medications and/or has severely active pSS Has received oral cyclophosphamide within 3 months or intravenous (IV) cyclophosphamide within 6 months prior to first administration of study intervention Has Sjogren's syndrome overlap syndromes where another confirmed autoimmune rheumatic or systemic inflammatory condition (for example, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], scleroderma, inflammatory bowel disease [IBD]) is the primary diagnosis or has clinical manifestations that, in the opinion of the investigator, or the sponsor or sponsor's representative, are likely to interfere with the investigator's ability to assess pSS manifestations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1: Placebo<br>Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids). | Other: Placebo<br>* Placebo infusion will be administered intravenously.<br>Drug: Standard of Care Treatment<br>* Standard of care treatment including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues, and/or one immunomodulator with or without low-dose glucocorticosteroids will be administered topically/orally.<br>|
| Experimental: Group 2: Nipocalimab Dose 1<br>Participants will receive nipocalimab dose 1 IV q2w through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids). | Drug: Nipocalimab<br>* Nipocalimab dose 1 and dose 2 infusions will be administered intravenously.<br>* Other names: M281;Drug: Standard of Care Treatment<br>* Standard of care treatment including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues, and/or one immunomodulator with or without low-dose glucocorticosteroids will be administered topically/orally.<br>|
| Experimental: Group 3: Nipocalimab Dose 2<br>Participants will receive nipocalimab dose 2 IV q2w through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids). | Drug: Nipocalimab<br>* Nipocalimab dose 1 and dose 2 infusions will be administered intravenously.<br>* Other names: M281;Drug: Standard of Care Treatment<br>* Standard of care treatment including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues, and/or one immunomodulator with or without low-dose glucocorticosteroids will be administered topically/orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) Score at Week 24 | The clinESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with primary Sjogren's syndrome. The clinESSDAI includes 11 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in European League Against Rheumatism (EULAR) Sjogren Syndrome Patient Reported Index (ESSPRI) Score at Week 24 | The ESSPRI is a patient-reported assessment of the severity of dryness, fatigue, and pain associated with primary Sjogren's Syndrome. Participants are 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 symptoms (dryness, fatigue or pain) to 10 maximal imaginable (dryness, fatigue, pain). A global score, calculated as the mean of the 3 domain scores, ranges from 0 to 10, with higher scores reflecting greater (worse) symptom severity. | Baseline to Week 24 | 
| Improvement of Greater than or Equal to (>=) 4 Points from Baseline in ESSDAI Score (Minimal Clinically Important Improvement) at Week 24 | The ESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with primary Sjogren's syndrome. The ESSDAI includes 11 to 12 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain. | Baseline to Week 24 | 
| Improvement of >= 4 Points from Baseline in clinESSDAI Score (Minimal Clinically Important Improvement) at Week 24 | The clinESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with Sjogren's syndrome. A minimal clinically important improvement in clinESSDAI is defined as a decrease of at least 4 points in the composite clinESSDAI score. | Baseline to Week 24 | 
| ESSPRI Response at Week 24 | ESSPRI response defined as a decrease of one point or a decrease of >= 15 percent (%) from baseline (minimal clinically important improvement) at Week 24 will be reported. | Week 24 | 
| Disease Response as Assessed by Sjögren's Tool for Assessing Response (STAR) Composite Score at Week 24 | Disease response by STAR of >= 5 at Week 24 will be reported. STAR is a composite tool that incorporates measures of disease activity (clinESSDAI), symptoms (ESSPRI), glandular function and systemic disease activity biomarkers to assess disease activity. | Week 24 | 
| Improvement in Disease Activity Level by >= 1 Level in at Least One clinESSDAI or ESSDAI Domain at Week 24 | Improvement in disease activity level by >= 1 level in at least one clinESSDAI or ESSDAI domain (biological, hematological, cutaneous, constitutional, lymphadenopathy and lymphoma, and glandular) at Week 24 will be reported. | Week 24 | 
| Improvement from Baseline in >= 3 of 5 Composite of Relevant Endpoints for Sjogren's Syndrome (CRESS) Categories at Week 24 | Improvement from baseline in >= 3 of 5 CRESS categories at week 24 will be reported. CRESS is a composite tool that incorporates measures of disease activity (clinESSDAI), symptoms (ESSPRI), glandular function and systemic inflammation to assess disease activity. | Baseline to Week 24 | 
| Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is 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 are defined as AEs with onset or worsening on or after date of first dose of study treatment. | Up to 30 weeks | 
| Percentage of Participants with Adverse Events of Special interests (AESIs) | Percentage of participants with AESIs will be reported. Treatment-emergent adverse events associated with the following situations are considered as AESIs: severe infections, severe hypoalbuminemia or hypogammaglobulinemia. | Up to 36 weeks | 
| Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs) | Treatment-emergent SAEs are defined as SAEs with onset or worsening on or after date of first dose of study treatment. | Up to 30 weeks | 
| Percentage of Participants with TEAEs Leading to Treatment Discontinuation | Percentage of participants with TEAEs leading to treatment discontinuation will be reported. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. | Up to 30 weeks | 
| Percentage of Participants with Clinically Significant Abnormalities in Vital Signs | Percentage of participants with clinically significant abnormalities in vital signs (including temperature, pulse/heart rate, respiratory rate, and blood pressure) through end of study visit will be reported. | Up to 36 weeks | 
| Percentage of Participants with Clinically Significant Abnormalities in Laboratory Parameters | Percentage of participants with clinically significant abnormalities in laboratory parameters (including hematology, blood chemistry, urinalysis, and blood coagulation) through end of study visit will be reported. | Up to 36 weeks | 
| Serum Concentration of Nipocalimab Over Time | Serum concentrations of nipocalimab over time in participants receiving active study intervention will be reported. | Up to Week 30 | 
| Number of Participants with Antibodies to Nipocalimab (Anti-drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs]) | Number of participants with antibodies to nipocalimab (ADAs and NAbs) in participants receiving active study intervention will be reported. | Up to Week 36 | 
| Number of Participants with Change from Baseline in Biomarkers | Number of participants with change from baseline in biomarkers (C-reactive protein [CRP], erythrocyte, total immunoglobulin [Ig]G, IgG1, IgG2, IgG3, IgG4) will be reported. | Baseline to Week 36 | 
| Number of Participants with Change from Baseline in Autoantibodies | Number of participants with change from baseline in autoantibodies (anti-Sjogren's syndrome related antigen A (anti-Ro/SSA), anti-Sjogren's syndrome related antigen B (anti-La/SSB), rheumatoid factor [RF] and antinuclear antibody [ANA]) will be reported. | Baseline to Week 36 |