A Study of Nipocalimab in Adult Participants With Active Systemic Lupus Erythematosus
- Conditions
- Systemic Lupus Erythematosus
- Interventions
- Registration Number
- NCT04882878
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 228
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: Placebo 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 \[GCs\]). Group 1: Placebo Standard-of-care treatment 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 \[GCs\]). Group 2: Nipocalimab Dose 1 Nipocalimab 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). Group 2: Nipocalimab Dose 1 Standard-of-care treatment 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). Group 3: Nipocalimab Dose 2 Nipocalimab 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). Group 3: Nipocalimab Dose 2 Standard-of-care treatment 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).
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4 Composite Response at Week 24 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 Outcome Measures
Name Time Method Time to First Flare Through Week 24 Up to 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.
Percentage of Participants Achieving SRI-4 Composite Response at Week 52 Week 52 Percentage of participants achieving SRI-4 composite response at Week 52 will be reported.
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 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.
Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs) Through Week 58 Up to 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.
Serum Concentration of Nipocalimab Over Time Up to Week 58 Serum concentrations of nipocalimab over time in participants receiving active study intervention will be reported.
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 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.
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 baseline arthritis (with at least 4 active joints at baseline) achieving \>= 50% reduction in active joints at Week 24 will be reported.
Percentage of Participants with >= 4 Point Improvement in SLE Disease Activity Index 2000 (SLEDAI-2K) at Week 24 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.
Percentage of Participants Achieving the British Isles Lupus Assessment Group (BILAG) Composite Lupus Assessment (BICLA) Response at Week 24 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.
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 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 \[g/dL\]).
Percentage of Participants with Treatment-emergent AEs leading to treatment discontinuation Through Week 58 Up to Week 58 Percentage of participants with treatment-emergent AEs leading to discontinuation of study intervention will be reported.
Number of Participants with Change from Baseline in Laboratory Parameters Over Time Up to Week 58 Number of participants with change from baseline in laboratory parameters (hematology, chemistry, urinalysis and lipid profile) over time will be reported.
Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) Through Week 58 Up to 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.
Number of Participants with Change from Baseline in Vital Signs Parameters Over Time Up to Week 58 Number of participants with change from baseline in vital sign parameters (temperature, pulse/heart rate, respiratory rate, and blood pressure) will be reported.
Number of Participants with Antibodies to Nipocalimab (Anti-Drug Antibodies [ADAs] and Neutralizing Antibodies [Nabs]) Up to Week 58 Number of participants with antibodies to nipocalimab (ADAs and Nabs) in participants receiving active study intervention will be reported.
Trial Locations
- Locations (86)
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Medbud-Clinic LLC
🇺🇦Kyiv, Ukraine
Valerius Medical Group & Research Center
🇺🇸Los Alamitos, California, United States
Desert Medical Advances
🇺🇸Rancho Mirage, California, United States
Wolverine Clinical Trials
🇺🇸Santa Ana, California, United States
South Coast Research Center
🇺🇸Miami, Florida, United States
Millennium Clinical Trials LLC
🇺🇸Westlake Village, California, United States
Bay Area Arthritis and Osteoporosis
🇺🇸Brandon, Florida, United States
GNP Research
🇺🇸Cooper City, Florida, United States
Advanced Clinical Research of Orlando
🇺🇸Ocoee, Florida, United States
Arthritis and Rheumatology Research Institute
🇺🇸Allen, Texas, United States
Precision Comprehensive Clinical Research Solutions
🇺🇸Colleyville, Texas, United States
Omega Research Consultants
🇺🇸Orlando, Florida, United States
Millennium Research
🇺🇸Ormond Beach, Florida, United States
Malopolskie Badania Kliniczne Sp z o o
🇵🇱Krakow, Poland
North Georgia Rheumatology, PC
🇺🇸Lawrenceville, Georgia, United States
Atlanta Research Center for Rheumatology
🇺🇸Marietta, Georgia, United States
West County Rheumatology
🇺🇸Saint Louis, Missouri, United States
DJL Clinical Research, PLLC
🇺🇸Charlotte, North Carolina, United States
Paramount Medical Research & Consulting
🇺🇸Middleburg Heights, Ohio, United States
Dr. Ramesh Gupta
🇺🇸Memphis, Tennessee, United States
Southwest Rheumatology Research LLC
🇺🇸Mesquite, Texas, United States
Epic Medical Research
🇺🇸Red Oak, Texas, United States
Rheumatology and Pulmonary Clinic
🇺🇸Beckley, West Virginia, United States
Centro Médico Reumatológico (OMI)
🇦🇷Buenos Aires, Argentina
Centro Privado de Medicina Familiar
🇦🇷Buenos Aires, Argentina
ARCIS Salud SRL Aprillus asistencia e investigacion
🇦🇷Caba, Argentina
Clinica Adventista Belgrano
🇦🇷Ciudad De Buenos Aires, Argentina
Hospital Italiano La Plata
🇦🇷La Plata, Argentina
Centro de Investigaciones Medicas Mar Del Plata
🇦🇷Mar Del Plata, Argentina
Instituto de Reumatologia - Ir Medical Center S.A.
🇦🇷Mendoza, Argentina
Centro de Investigaciones Medicas Tucuman
🇦🇷San Miguel De Tucuman, Argentina
Multiprofile Hospital for Active Treatment Plovdiv
🇧🇬Plovdiv, Bulgaria
Diagnostic-Consultative Center (DCC) Aleksandrovska
🇧🇬Sofia, Bulgaria
UMHAT St. Ivan Rilski
🇧🇬Sofia, Bulgaria
Clinica de la Costa SAS
🇨🇴Barranquilla, Colombia
Centro de Investigacion Medico Asistencial SAS - CIMEDICAL SAS
🇨🇴Barranquilla, Colombia
Centro de Investigación en Reumatología y especialidades médicas S.A.S. - CIREEM S.A.S.
🇨🇴Bogotá, Colombia
Servimed S A S
🇨🇴Bucaramanga, Colombia
IPS Preventive Care SAS
🇨🇴Chia, Colombia
Praxis Dr. med. Beate Schwarz - Germany
🇩🇪Langenau, Germany
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Betegapolo Irgalmas Rend Budai Irgalmasrendi Korhaz
🇭🇺Budapest, Hungary
Bekes Varmegyei Kozponti Korhaz Pandy Kalman Tagkorhaz
🇭🇺Gyula, Hungary
Belvarosi Egeszseghaz Kft. (Leda-Platan Maganklinika es Sebeszeti Kozpont)
🇭🇺Zalaegerszeg, Hungary
National Hospital Organization Chiba East Hospital
🇯🇵Chiba, Japan
National Hospital Organization Kyushu Medical Center
🇯🇵Fukuoka, Japan
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
National Center for Global Health and Medicine Kohnodai hospital
🇯🇵Ichikawa, Japan
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya-shi, Japan
Hosp. de Navarra
🇪🇸Pamplona, Spain
St Marianna University Hospital
🇯🇵Kanagawa, Japan
National Hospital Organization Osaka Minami Medical Center
🇯🇵Kawachi Nagano, Japan
Osaka Medical and Pharmaceutical University Hospital
🇯🇵Takatsuki, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka, Japan
Tohoku University Hospital
🇯🇵Sendai shi, Japan
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain
St. Luke's International Hospital
🇯🇵Tokyo, Japan
Fujita Health University Hospital
🇯🇵Toyoake, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba, Japan
Szpital Uniwersytecki Nr 2 w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Nzoz Bif Med
🇵🇱Bytom, Poland
Centrum Medyczne Plejady
🇵🇱Krakow, Poland
NZOZ Lecznica MAK MED S C
🇵🇱Nadarzyn, Poland
Twoja Przychodnia Poznanskie Centrum Medyczne
🇵🇱Poznan, Poland
AI Centrum Medyczne
🇵🇱Poznan, Poland
Prywatna Praktyka Lekarska Prof Um Dr Hab Med Pawel Hrycaj
🇵🇱Poznan, Poland
Uniwersytecki Szpital Kliniczny w Rzeszowie
🇵🇱Rzeszow, Poland
MICS Centrum Medyczne Warszawa
🇵🇱Warszawa, Poland
Panorama Medical Centre
🇿🇦Cape Town, South Africa
Excellentis Clinical trial Consultants
🇿🇦George, South Africa
Winelands Rheumatology Centre
🇿🇦Stellenbosch, South Africa
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taipei Medical University
🇨🇳Taipei, Taiwan
Municipal Non-Profit Enterprise 'Chernihiv Regional Hospital' of Chernihiv Regional Council
🇺🇦Chernihiv, Ukraine
Municipal Non-Profit Enterprise of Kharkiv Regional Council 'Regional Clinical Hospital'
🇺🇦Kharkiv, Ukraine
Medical Center 'Ok Clinic' of International Institute of Clinical Research LLC
🇺🇦Kyiv, Ukraine
Kyiv Railway Clinical Hospital #2 Of Branch 'Health Center' Of The Company 'Ukrainian Railway'
🇺🇦Kyiv, Ukraine
Medical Center 'Consylium Medical'
🇺🇦Kyiv, Ukraine
Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council
🇺🇦Odessa, Ukraine
ME Poltava Regional Clinical Hospital named after M.V. Sklifosovsky of Poltava Regional Consuil
🇺🇦Poltava, Ukraine
MNPE 'Vinnytsia Regional Clinical Hospital named after M.I. Pyrogov of Vinnytsia Regional Council'
🇺🇦Vinnytsia, Ukraine
Medical Center LLC 'Modern Clinic'
🇺🇦Zaporizhzhya, Ukraine