A Study of Nipocalimab in Adult Participants With Active Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of nipocalimab versus placebo in participants with active systemic lupus erythematosus (SLE).

Detailed Description
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SLE is a complex, immune-mediated inflammatory disorder of unknown etiology that can affect almost any organ system and follows a waxing and waning disease course. In SLE, the immune system attacks the body cells and tissues and the resulting inflammation and tissue damage can harm the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system. 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). Thus, nipocalimab, a FcRn antibody, has potential in treatment of SLE through lowering of pathogenic IgGs and immune complexes. The study will consist of a Screening Period (less than or equal to [<=] 6 Weeks), double-blind Treatment Period (52 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 tests (hematology, chemistry, urinalysis, and lipid profile) and vital signs. The total duration of the study is up to 64 weeks.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Nipocalimab in Adult Participants With Active Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

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: Has a clinical diagnosis of systemic lupus erythematosus (SLE) greater than or equal to (>=) 6 months prior to the screening visit and according to Systemic Lupus International Collaborating Clinics (SLICC)-2012 classification criteria: at least 4 criteria fulfilled, with at least 1 clinical criterion and 1 immunologic criterion Has at least 1 BILAG (british isles lupus assessment group) A and/or 2 BILAG B scores observed during screening Must have at least moderately active SLE, as defined as systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) score >= 6 at screening visit. Must also have SLEDAI 2K >= 4 for clinical features (that is, SLEDAI-2K score excluding headache and laboratory abnormalities) present at Week 0 prior to randomization Has a CLASI (cutaneous lupus erythematosus disease area and severity index) activity score of at least 6 (excluding diffuse non-inflammatory alopecia) or at least 4 joints with pain and signs of inflammation (active joints) at screening or at Week 0, or both At least 1 unequivocally positive autoantibody test including antinuclear antibodies (ANA) (>= 1:80) and/or anti-double stranded deoxyribonucleic acid (dsDNA) antibodies (level >= 75 international units/milliliter [IU/mL]) and/or anti-Smith antibodies (>120 Absorbance unit/milliliter [AU/mL]) detected during screening Must be receiving 1 or more of the following protocol-permitted, systemic standard-of-care treatments prior to first administration of study intervention at a stable dose: oral glucocorticoids, antimalarial or up to 2 immunomodulatory drugs Exclusion Criteria: Current or history of, severe, progressive, or uncontrolled renal disease, with the exception of active lupus nephritis (LN). Have severe active LN as determined by sponsor (or designee) adjudication. Control of renal disease must be documented with at least 2 measurements of proteinuria or urine protein/creatinine ratio (UPCR) over the 6 months prior to screening Has any unstable or progressive manifestation of SLE that is likely to warrant escalation in therapy beyond permitted background medications Confirmed or suspected inflammatory diseases that might confound the evaluations of efficacy Has a severe infection including opportunistic infections requiring parenteral anti-infectives, and/or hospitalization within 8 weeks prior to screening Has received a single B-cell targeting agent within 3 months prior to first administration of study intervention

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
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 two weeks (q2w) through Week 50 along with standard-of-care treatments (that is, immunomodulators, antimalarial drugs and Glucocorticoids [GCs]). | Other: Placebo<br>* Placebo will be administered intravenously.<br>Drug: Standard-of-care treatment<br>* Standard-of-care treatment including immunomodulators, antimalarial drugs and GCs will be administered orally.<br>|
| Experimental: Group 2: Nipocalimab Dose 1<br>Participants will receive nipocalimab dose 1 intravenously (IV) q2w through Week 50 along with standard-of-care treatments (that is, immunomodulators, antimalarial drugs and GCs). | Drug: Nipocalimab<br>* Nipocalimab dose 1 and dose 2 will be administered intravenously.<br>* Other names: M281;Drug: Standard-of-care treatment<br>* Standard-of-care treatment including immunomodulators, antimalarial drugs and GCs will be administered orally.<br>|
| Experimental: Group 3: Nipocalimab Dose 2<br>Participants will receive nipocalimab dose 2 intravenously (IV) q2w through Week 50 along with standard-of-care treatments (that is, immunomodulators, antimalarial drugs and GCs). | Drug: Nipocalimab<br>* Nipocalimab dose 1 and dose 2 will be administered intravenously.<br>* Other names: M281;Drug: Standard-of-care treatment<br>* Standard-of-care treatment including immunomodulators, antimalarial drugs and GCs will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4 Composite Response at Week 24 | SLE SRI-4 composite response is a composite of at least 4-point improvement in SLE Disease Activity Index 2000(SLEDAI-2K), no worsening in British Isles Lupus Assessment Group (BILAG), no worsening in Physician's Global Assessment of Disease Activity score (PGA) and not meeting study treatment failure criteria. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Baseline Active Mucocutaneous Lupus Manifestations (Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI] Activity Score >= 6) Achieving >= 50 Percent (%) Reduction in the CLASI Activity Score at Week 24 | Percentage of participants achieving at least 50% improvement in CLASI Activity Score at Week 24 will be reported in participants with a CLASI Activity Score of 6 or greater at baseline. Cutaneous lupus disease activity and severity will be measured by the CLASI. The CLASI is an instrument to assess the disease activity and damage caused to the skin for cutaneous lupus erythematosus participants with or without systemic involvement. The CLASI consists of 2 scores; the first summarizes the activity of the disease while the second is a measure of the damage caused by the disease. | Week 24 | 
| Percentage of Participants with Baseline Arthritis (with at Least 4 Active Joints at Baseline) Achieving >= 50% Reduction in Active Joints at Week 24 | Percentage of participants with baseline arthritis (with at least 4 active joints at baseline) achieving >= 50% reduction in active joints at Week 24 will be reported. | Week 24 | 
| Percentage of Participants with >= 4 Point Improvement in SLE Disease Activity Index 2000 (SLEDAI-2K) at Week 24 | Percentage of participants achieving at least 4 point improvement in SLEDAI-2K will be reported. The SLEDAI-2K is an established, validated SLE activity index. It is based on the presence of 24 features in 9 organ systems and measures disease activity in SLE participants at the time of the visit or in the previous 30 days; the index is weighted according to the feature. Features are scored by the assessing physician if present at the time of the visit or within the last 30 days, with more severe features having higher scores, and then simply added to determine the total SLEDAI-2K score, which ranges from 0 to 105, with higher scores representing increased disease activity. | Week 24 | 
| Percentage of Participants Achieving the British Isles Lupus Assessment Group (BILAG) Composite Lupus Assessment (BICLA) Response at Week 24 | Percentage of participants achieving BICLA Response (BILAG-2004 disease activity improvement without worsening, and without worsening of SLEDAI-2K or PGA compared to baseline) at Week 24 will be reported. | Week 24 | 
| Time to First Flare Through Week 24 | Time to first flare through Week 24, with flare defined as either 1 or more new BILAG A or 2 or more new BILAG B scores will be reported. | Up to Week 24 | 
| Percentage of Participants Achieving SRI-4 Composite Response at Week 52 | Percentage of participants achieving SRI-4 composite response at Week 52 will be reported. | Week 52 | 
| Percentage of Participants Receiving >= 10 milligram/day (mg/day) Prednisone or Equivalent at Baseline who Achieve Week 6-16 Glucocorticoid (GC) Taper Goal (at Week 16 to <= 7.5 mg/day Prednisone or Equivalent) and Maintain that Reduction Until Week 24 | Percentage of participants receiving >= 10 mg/day prednisone or equivalent at baseline who achieve Week 6-16 GC taper goal (at Week 16 to <= 7.5 mg/day prednisone or equivalent) and maintain that reduction until Week 24 will be reported. | Up to Week 24 | 
| Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) Through Week 58 | 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 Week 58 | 
| Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs) Through Week 58 | SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. Treatment-emergent SAEs are defined as SAEs with onset or worsening on or after date of first dose of study treatment. | Up to Week 58 | 
| Percentage of Participants with Treatment-emergent Adverse Events of Special interests (AESIs) Through Week 58 | Percentage of participants with treatment-emergent AESIs will be reported. Treatment-emergent adverse events associated with the following situations are considered as AESIs: infections that are severe or require intravenous anti-infective or operative/invasive intervention, hypoalbuminemia with albumin less than (<) 20 gram/liter (g/L) (<2.0 gram/deciliter [g/dL]). | Up to Week 58 | 
| Percentage of Participants with Treatment-emergent AEs leading to treatment discontinuation Through Week 58 | Percentage of participants with treatment-emergent AEs leading to discontinuation of study intervention will be reported. | Up to Week 58 | 
| Number of Participants with Change from Baseline in Laboratory Parameters Over Time | Number of participants with change from baseline in laboratory parameters (hematology, chemistry, urinalysis and lipid profile) over time will be reported. | Up to Week 58 | 
| Number of Participants with Change from Baseline in Vital Signs Parameters Over Time | Number of participants with change from baseline in vital sign parameters (temperature, pulse/heart rate, respiratory rate, and blood pressure) will be reported. | Up to Week 58 | 
| Serum Concentration of Nipocalimab Over Time | Serum concentrations of nipocalimab over time in participants receiving active study intervention will be reported. | Up to Week 58 | 
| 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 58 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus, SLE, Nipocalimab, Lupus SLE