A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Nipocalimab in Adult Participants With Active Systemic Lupus Erythematosus
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 228
- Locations
- 86
- Primary Endpoint
- Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4 Composite Response at Week 24
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy of nipocalimab versus placebo in participants with active systemic lupus erythematosus (SLE).
Detailed Description
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Group 1: Placebo
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 \[GCs\]).
Intervention: Placebo
Group 1: Placebo
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 \[GCs\]).
Intervention: Standard-of-care treatment
Group 2: Nipocalimab Dose 1
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).
Intervention: Nipocalimab
Group 2: Nipocalimab Dose 1
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).
Intervention: Standard-of-care treatment
Group 3: Nipocalimab Dose 2
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).
Intervention: Nipocalimab
Group 3: Nipocalimab Dose 2
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).
Intervention: Standard-of-care treatment
Outcomes
Primary Outcomes
Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4 Composite Response at Week 24
Time Frame: 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.
Secondary Outcomes
- Time to First Flare Through Week 24(Up to Week 24)
- Percentage of Participants Achieving SRI-4 Composite Response at Week 52(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(Up to Week 24)
- Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs) Through Week 58(Up to Week 58)
- Serum Concentration of Nipocalimab Over Time(Up to Week 58)
- 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(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(Week 24)
- Percentage of Participants with >= 4 Point Improvement in SLE Disease Activity Index 2000 (SLEDAI-2K) at Week 24(Week 24)
- Percentage of Participants Achieving the British Isles Lupus Assessment Group (BILAG) Composite Lupus Assessment (BICLA) Response at Week 24(Week 24)
- Percentage of Participants with Treatment-emergent Adverse Events of Special interests (AESIs) Through Week 58(Up to Week 58)
- Percentage of Participants with Treatment-emergent AEs leading to treatment discontinuation Through Week 58(Up to Week 58)
- Number of Participants with Change from Baseline in Laboratory Parameters Over Time(Up to Week 58)
- Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) Through Week 58(Up to Week 58)
- Number of Participants with Change from Baseline in Vital Signs Parameters Over Time(Up to Week 58)
- Number of Participants with Antibodies to Nipocalimab (Anti-Drug Antibodies [ADAs] and Neutralizing Antibodies [Nabs])(Up to Week 58)