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

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04882878
• Other study ID #: CR109011
• Secondary ID: 2020-005569-1480
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 20, 2021
• Est. completion date: December 26, 2024

Study information

• Verified date: May 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 228
• Est. completion date: December 26, 2024
• Est. primary completion date: May 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Other:
• Placebo
Placebo will be administered intravenously.

Drug:
• Nipocalimab
Nipocalimab dose 1 and dose 2 will be administered intravenously.
• Standard-of-care treatment
Standard-of-care treatment including immunomodulators, antimalarial drugs and GCs will be administered orally.

Locations

Country	Name	City	State
Argentina	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
Bulgaria	Multiprofile Hospital for Active Treatment Plovdiv	Plovdiv
Bulgaria	UMHAT St. Ivan Rilski	Sfia
Bulgaria	Diagnostic-Consultative Center (DCC) Aleksandrovska	Sofia
Colombia	Centro de Investigacion Medico Asistencial SAS - CIMEDICAL SAS	Barranquilla
Colombia	Clinica de la Costa 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
Germany	Praxis Dr. med. Beate Schwarz - Germany	Langenau
Germany	Universitaetsklinikum Leipzig	Leipzig
Hungary	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
Japan	National Hospital Organization Chibahigashi National Hospital	Chiba
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	National Center for Global Health and Medicine Kohnodai hospital	Ichikawa
Japan	St Marianna University Hospital	Kanagawa
Japan	National Hospital Organization Osaka Minami Medical Center	Kawachi Nagano
Japan	National Hospital Organization Nagoya Medical Center	Nagoya-shi
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Tohoku University Hospital	Sendai shi
Japan	Osaka Medical and Pharmaceutical University Hospital	Takatsuki
Japan	St. Luke's International Hospital	Tokyo
Japan	Fujita Health University Hospital	Toyoake
Japan	University of Tsukuba Hospital	Tsukuba
Poland	Szpital Uniwersytecki Nr 2 w Bydgoszczy	Bydgoszcz
Poland	Nzoz Bif Med	Bytom
Poland	Centrum Medyczne Plejady	Krakow
Poland	Malopolskie Badania Kliniczne Sp z o o	Krakow
Poland	NZOZ Lecznica MAK MED S C	Nadarzyn
Poland	AI Centrum Medyczne	Poznan
Poland	Prywatna Praktyka Lekarska, Prof. UM dr hab. med. Pawel Hrycaj	Poznan
Poland	Twoja Przychodnia Poznanskie Centrum Medyczne	Poznan
Poland	Uniwersytecki Szpital Kliniczny w Rzeszowie	Rzeszow
Poland	MICS Centrum Medyczne Warszawa	Warszawa
South Africa	Panorama Medical Centre	Cape Town
South Africa	Excellentis Clinical trial Consultants	George
South Africa	Winelands Rheumatology Centre	Stellenbosch
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. de Navarra	Pamplona
Spain	Corporacio Sanitari Parc Tauli	Sabadell
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taipei Medical University	Taipei
Ukraine	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	Kyiv Railway Clinical Hospital #2 Of Branch 'Health Center' Of The Company 'Ukrainian Railway'	Kyiv
Ukraine	Medbud-Clinic LLC	Kyiv
Ukraine	Medical Center 'Consylium Medical'	Kyiv
Ukraine	Medical Center 'Ok Clinic' of International Institute of Clinical Research LLC	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
United States	Arthritis and Rheumatology Research Institute	Allen	Texas
United States	Rheumatology and Pulmonary Clinic	Beckley	West Virginia
United States	Bay Area Arthritis and Osteoporosis	Brandon	Florida
United States	DJL Clinical Research, PLLC	Charlotte	North Carolina
United States	Precision Comprehensive Clinical Research Solutions	Colleyville	Texas
United States	GNP Research	Cooper City	Florida
United States	North Georgia Rheumatology, PC	Lawrenceville	Georgia
United States	Valerius Medical Group & Research Center	Los Alamitos	California
United States	Atlanta Research Center for Rheumatology	Marietta	Georgia
United States	Dr. Ramesh Gupta	Memphis	Tennessee
United States	Southwest Rheumatology Research LLC	Mesquite	Texas
United States	South Coast Research Center	Miami	Florida
United States	Paramount Medical Research & Consulting	Middleburg Heights	Ohio
United States	Advanced Clinical Research of Orlando	Ocoee	Florida
United States	Omega Research Consultants	Orlando	Florida
United States	Millennium Research	Ormond Beach	Florida
United States	Desert Medical Advances	Rancho Mirage	California
United States	Epic Medical Research	Red Oak	Texas
United States	West County Rheumatology	Saint Louis	Missouri
United States	Wolverine Clinical Trials	Santa Ana	California
United States	Millennium Clinical Trials LLC	Simi Valley	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Colombia,  Germany,  Hungary,  Japan,  Poland,  South Africa,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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