A Study to Learn About the Safety of Litifilimab (BIIB059) Injections and Whether They Can Improve Symptoms of Adult Participants Who Have Systemic Lupus Erythematosus (TOPAZ-1)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Litifilimab (BIIB059) in Adult Participants With Active Systemic Lupus Erythematosus Receiving Background Nonbiologic Lupus Standard of Care

In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with systemic lupus erythematosus (SLE). The study will focus on participants who have active disease and are already taking standard of care medications. These may include antimalarials, steroids, and immunosuppressants.

The main objective of the study is to learn about the effect litifilimab has on lowering the activity of the disease. The main question researchers want to answer is:

- How many participants have an improvement in their symptoms after 52 weeks of treatment? Researchers will answer this and other questions by measuring the symptoms of SLE over time using a variety of scoring tools. These include the SLE Responder Index (SRI), the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), the British Isles Lupus Activity Group-2004 index (BILAG-2004), and the BILAG-BASED Combined Lupus Assessment (BICLA), among others.

Researchers will also learn more about the safety of litifilimab. They will study how participants' immune systems respond to litifilimab. Additionally, they will measure the effect litifilimab and SLE have on the quality of life of participants using a group of questionnaires.

The study will be done as follows:

• After screening, participants will be randomized to receive either a high or low dose of litifilimab, or placebo. A placebo looks like the study drug but contains no real medicine.
• All participants will receive either litifilimab or placebo as injections under the skin once every 4 weeks. The treatment period will last 52 weeks. Participants will continue to take their standard of care medications.
• Neither the researchers nor the participants will know if the participants are receiving litifilimab or placebo.
• There will be a follow-up safety period that lasts up to 24 weeks.
• In total, participants will have up to 22 study visits. The total study duration for participants will be up to 80 weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Drug: Placebo; Drug: Litifilimab

Detailed Description

The primary objective of the study is to demonstrate the efficacy of litifilimab compared with placebo in participants with active SLE, who are receiving background lupus standard of care (SOC) therapy in reducing disease activity.

The secondary objectives of this study are to demonstrate efficacy of litifilimab compared with placebo in participants with active SLE, who are receiving background lupus SOC therapy in reducing disease activity and occurrence of flare up to Week 52; to demonstrate organ-specific efficacy of litifilimab compared with placebo in participants with active SLE, who are receiving background lupus SOC therapy in reducing joint disease activity and skin disease activity; to demonstrate and evaluate effect of litifilimab compared with placebo in reducing oral corticosteroid(s) (OCS) use; to evaluate additional efficacy of litifilimab compared with placebo in reducing disease activity with additional disease activity measures; assess the difference between litifilimab and placebo on participant reported health-related quality of life (HRQoL), symptoms, and impacts of SLE; to evaluate the safety, tolerability and immunogeneicty of litifilimab in participants with active SLE.

• Study Type: Interventional
• Enrollment (Actual): 548
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Footscray, Victoria, Australia, 3011
      • Footscray Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Brazil
  • São Paulo, Brazil, 04037-030
    • Rdss Ricardo Diaz Scientific Solution
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-370
      • HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29055-450
      • CEDOES - Diagnóstico e Pesquisa
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40150-150
      • Clínica SER da Bahia
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • L2IP - Instituto de Pesquisas Clínicas Ltda.
  • Mato Grosso
    • Cuiabá, Mato Grosso, Brazil, 78043-142
      • Oncovida - Centro de Onco-Hematologia de Mato Grosso
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Santa Casa de Misericordia de Belo Horizonte
    • Juiz de Fora, Minas Gerais, Brazil, 36010-570
      • CMiP - Centro Mineiro de Pesquisa
  • Paraná
    • Curitiba, Paraná, Brazil, 80030-110
      • CETI - Centro de Estudos em Terapias Inovadoras Ltda.
  • Rio Grande do Sul
    • Lajeado, Rio Grande do Sul, Brazil, 95900-000
      • Hospital Bruno Born
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-001
      • Hospital Moinhos de Vento
    • Porto Alegre, Rio Grande do Sul, Brazil, 90480-000
      • LMK Serviços Médicos S/S Ltda
  • São Paulo
    • Sao Jose Rio Preto, São Paulo, Brazil, 15090-000
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto
    • São Bernardo do Campo, São Paulo, Brazil, 09715-090
      • Centro Multidisciplinar de Estudos Clínicos - CEMEC
    • São Paulo, São Paulo, Brazil, 04266-010
      • CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos
    • Valinhos, São Paulo, Brazil, 13271-130
      • A2Z Clinical Centro Avancado de Pesquisa Clinica
• Bulgaria
  • Plovdiv, Bulgaria, 4003
    • UMHAT-Plovdiv AD
  • Plovdiv, Bulgaria, 4002
    • UMHAT "Pulmed" OOD
  • Plovdiv, Bulgaria, 4000
    • DCC 'Sv. Georgi', EOOD
  • Rousse, Bulgaria, 7002
    • DCC 1 - Ruse, EOOD
  • Sofia, Bulgaria, 1510
    • Medical Center Hera EOOD
  • Sofia, Bulgaria, 1431
    • Dcc 'Alexandrovska', Eood
  • Sofia, Bulgaria, 1606
    • Military Medical Academy - MHAT - Sofia
  • Sofia, Bulgaria, 1612
    • UMHAT 'Sv. Ivan Rilski', EAD
• Chile
  • Osorno, Chile, 5290000
    • Clinica Alemana de Osorno
  • Santiago, Chile, 7500710
    • BioMedica Research Group
  • Santiago, Chile, 7500000
    • Centro Medico Prosalud
  • Santiago, Chile, 7500010
    • Interin
  • Santiago, Chile, 8331143
    • CeCim Biocinetic
  • Santiago, Chile, 7500571
    • CTR Estudios
  • Santiago, Chile, 7500587
    • Enroll Spa
  • Valdivia, Chile, 5090000
    • Clinical Research Chile SpA.
• France
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • Groupe Hospitalier Pellegrin - Hôpital Pellegrin
  • Herault
    • Montpellier, Herault, France, 34295
      • Hopital Lapeyronie
  • Puy De Dome
    • Clermont-Ferrand, Puy De Dome, France, 63003
      • CHU Clermont Ferrand - Hopital Gabriel Montpied
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens Laiko
  • Athens, Greece, 11521
    • NNA Hospita;
  • Athens, Greece, 12462
    • University General Hospital 'Attikon'
• Mexico
  • Chihuahua City, Mexico, 31000
    • Investigacion y Biomedicina de Chihuahua, S.C.
  • Durango, Mexico, 34080
    • Centro de Investigacion y Atencion Integral Durango CIAID
  • Veracruz, Mexico, 91900
    • FAICIC S. de R.L. de C.V.
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Clinica de Investigacion en Reumatologia y Obesidad S.C.
    • Guadalajara, Jalisco, Mexico, 44130
      • Diseño y Planeacion en Investigacion Medica S.C.
    • Guadalajara, Jalisco, Mexico, 44160
      • Centro de Investigacion Farmaceutica Especializada de Occidente S.C
    • Guadalajara, Jalisco, Mexico, 44959
      • Centro de investigacion medica y reumatologia
  • Mexico City
    • Mexico City, Mexico City, Mexico, 14080
      • Instituto Nacional de Ciencias Medicas y Nutricion Dr. Salvador Zubiran
    • Mexico City, Mexico City, Mexico, 3720
      • Centro de Investigacion Clínica GRAMEL S.C
    • Mexico City, Mexico City, Mexico, 6700
      • Clinstile, S.A. de C.V.
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62448
      • Consultorio Privado Dr. Miguel Cortes Hernandez
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64000
      • Accelerium S. de R.L. de C.V.
    • Monterrey, Nuevo León, Mexico, 64460
      • Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
  • Yucatán
    • Mérida, Yucatán, Mexico, 97000
      • Centro Peninsular de Investigacion Clinica, SCP
    • Mérida, Yucatán, Mexico, 97070
      • Medical Care & Research SA de CV
    • Mérida, Yucatán, Mexico, 97000
      • Unidad de Atencion Medica e Investigacion en Salud S.C.
• Peru
  • Arequipa, Peru, 40103
    • Hogar Clínica San Juan de Dios - Arequipa
  • Lima, Peru, LIMA 33
    • Invest Clinicas Sac Inst de Ginecologia y Reproduccion
  • Lima, Peru, LIMA 11
    • Hospital Nacional Edgardo Rebagliati Martins
  • Lima, Peru, LIMA 29
    • HMA - Hospital Maria Auxiliadora
  • Lima, Peru, Lima 11
    • Centro de Investigacion Clinica Immunoreumatologioa
• Philippines
  • Cebu City, Philippines, 6000
    • Chong Hua Hospital
  • City of Taguig, Philippines, 1642
    • Ospital ng Makati
  • Davao City, Philippines, 8000
    • Davao Doctors Hospital
  • Iloilo City, Philippines, 5000
    • The Medical City Iloilo
  • Lipa City, Philippines, 4217
    • Mary Mediatrix Medical Center
  • Mabalacat, Pampanga, Philippines, 2023
    • The Medical City Clark
  • Manila, Philippines, 1000
    • Philippine General Hospital
  • Manila, Philippines, 1000
    • Manila Doctors Hospital
  • Manila, Philippines, 1000
    • Medical Center Manila
  • Manila, Philippines, 1012
    • Jose R. Reyes Memorial Medical Center
  • Quenzon City, Philippines, 1102
    • St. Luke's Medical Center
  • Quezon City, Metro Manila, Philippines, 1118
    • Far Eastern University - Dr. Nicanor Reyes Medical Foundation
  • San Fernando City, La Union, Philippines, 2500
    • Lorma Medical Center
• Poland
  • Bialystok, Poland, 15-707
    • Nova Reuma Domysławska i Rusiłowicz, Spółka Partnerska Lekarza Reumatologa i Fizjoterapeuty
  • Bydgoszcz, Poland, 85-605
    • Centrum Medyczne Intercor Sp. z o.o
  • Bydgoszcz, Poland, 87-100
    • Szpital Uniwersytecki nr 2 im.dr J. Biziela
  • Bytom, Poland, 41-902
    • Nzoz Bif-Med
  • Krakow, Poland, 30-363
    • Centrum Medyczne Plejady
  • Krakow, Poland, 30-002
    • Malopolskie Badania Kliniczne
  • Krakow, Poland, 31-023
    • Centrum Medyczne ALL-MED
  • Krakow, Poland, 30-727
    • Pratia MCM Krakow
  • Lublin, Poland, 20-607
    • Reumed Spolka z o.o.
  • Malbork, Poland, 82-200
    • Centrum Badawcze Panaceum Agnieszka Brzezicka, Magdalena Lenkiewicz Sp. z o.o.
  • Nowa Sól, Poland, 67-100
    • Twoja Przychodnia NCM
  • Poznan, Poland, 61-397
    • Prywatna Praktyka Lekarska prof Pawel Hrycaj
  • Warsaw, Poland, 00-874
    • MICS Centrum Medyczne Warszawa
  • Warsaw, Poland, 00-719
    • Przychodnia Care Access Warszawa
  • Wroclaw, Poland, 53-224
    • Niepubliczny Zakład Opieki Zdrowotnej 'Biogenes' Sp. z o.o.
• South Korea
  • Busan, South Korea, 49201
    • Dong-A University Hospital
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Seoul, South Korea, 5505
    • Asan Medical Center
  • Seoul, South Korea, 4763
    • Hanyang University Seoul Hospital
  • Seoul, South Korea, 5030
    • Konkuk University Medical Center
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, South Korea, 16499
      • Ajou University Hospital
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Granada, Spain, 18016
    • Hospital Universitario San Cecilio
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Seville, Spain, 41010
    • Hospital Quironsalud Infanta Luisa
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
    • Valladolid, Cantabria, Spain, 47012
      • Hospital Universitario Rio Hortega
• Sweden
  • Stockholm, Sweden, SE-171 76
    • Karolinska Universitetssjukhuset Solna
  • Uppasala, Sweden, 75185
    • Akademiska Sjukhuset
  • Örebro, Sweden, 70185
    • Universitetssjukhuset Orebro
• Taiwan
  • Kaohsiung City, Taiwan, 833
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40201
    • Chung Shan Medical University Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital,Linkou
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Tilda Research Birmingham
  • California
    • Beverly Hills, California, United States, 90211
      • Wallace Rheumatic Study Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Mission Hills, California, United States, 91345
      • Providence Facey Medical Foundation
    • San Diego, California, United States, 92103
      • University of California San Diego School of Medicine
    • Thousand Oaks, California, United States, 91360
      • SCLA Management
    • Torrance, California, United States, 90509
      • Harbor-UCLA Medical Center
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials, Inc.
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007-2113
      • Georgetown University Hospital-Medstar
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis & Rheumatic Disease Specialties
    • Avon Park, Florida, United States, 33825
      • Highlands Rheumatology
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida - Corporate
    • Coral Springs, Florida, United States, 33065
      • Believe Clinical Trials
    • DeBary, Florida, United States, 32713
      • Omega Research Consultants
    • Fort Lauderdale, Florida, United States, 33334
      • Centre for Rheumatology, Immunology and Arthritis
    • Hollywood, Florida, United States, 33024
      • GNP Research at Mark Jaffe, MD
    • Margate, Florida, United States, 33063
      • LIFE Clinical Trials
    • Miami Lakes, Florida, United States, 33014
      • Charisma Medical and Research Center
    • Orlando, Florida, United States, 32806
      • Rheumatology Associates of Central Florida
    • Tampa, Florida, United States, 33613
      • AdventHealth Medical Group
    • Tampa, Florida, United States, 33614
      • Vantage Clinical Trials
  • Georgia
    • Kennesaw, Georgia, United States, 30144
      • Rheumatology care of Georgia
    • Marietta, Georgia, United States, 30060
      • Atlanta Research Center for Rheumatology LLC
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Accurate Clinical Research Inc.
  • Michigan
    • Flint, Michigan, United States, 48504
      • AA MRC LLC Ahmed Arif Medical Research Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Medical Group
  • New York
    • Brooklyn, New York, United States, 11201
      • Joseph S. and Diane H. Steinberg Ambulatory Care Center
    • New Hyde Park, New York, United States, 11042-1118
      • Northwell Health Center for Advanced Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Joint and Muscle Research Institute
    • Greensboro, North Carolina, United States, 27405
      • Medication Management, LLC
    • Salisbury, North Carolina, United States, 28144
      • OnSite Clinical Solutions, LLC - Charlotte
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research & Consulting, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Hightower Clinical
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Ramesh C Gupta, MD
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Allen, Texas, United States, 75013
      • PrimeCare 360
    • Colleyville, Texas, United States, 76034
      • Precision Comprehensive Clinical Research Solutions
    • Colleyville, Texas, United States, 76034-5913
      • Precision Comprehensive Clinical Research Solution
    • Corpus Christi, Texas, United States, 78415
      • Arthritis Care Texas
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions, Inc.
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center
    • Houston, Texas, United States, 77089
      • Accurate Clinical Management LLC
    • Humble, Texas, United States, 77346
      • Accurate Clinical Research, Inc.
    • Stafford, Texas, United States, 77477
      • Accurate Clinical Research
    • Sugar Land, Texas, United States, 77407
      • Fort Bend Rheumatology Associates
    • The Woodlands, Texas, United States, 77382
      • Advanced Rheumatology of Houston
    • Webster, Texas, United States, 77598
      • CLS Research Ctr, PLLC
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participant must be diagnosed with systemic lupus erythematosus (SLE) at least 24 weeks prior to screening and must meet the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria for SLE at screening by a qualified physician.
• Participant has a modified Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score ≥ 6 (excluding alopecia, fever, lupus-related headache, and organic brain syndrome) at screening (adjudicated).
• Participant has a modified clinical SLEDAI-2K score ≥ 4 (excluding anti-dsDNA, low complement component 3 (C3) and/or complement component 4 (C4), alopecia, fever, lupus-related headache, and organic brain syndrome) at Screening (adjudicated) and randomization.
• Participant has BILAG-2004 grade A in ≥ 1 organ system or BILAG-2004 grade B in ≥ 2 organ systems at Screening (adjudicated) and randomization.

• Participant must be treated with one of the following background nonbiologic lupus SOC therapies, initiated ≥ 12 weeks prior to Screening and at stable dose ≥ 4 weeks prior to randomization:

  1. Antimalarials as stand-alone treatment
  2. Antimalarial treatment in combination with OCS and/or a single immunosuppressant
  3. Treatment with OCS and/or a single immunosuppressant

Key Exclusion Criteria:

• History of or positive test result for human immunodeficiency virus (HIV).
• Current hepatitis C infection (defined as positive hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid [RNA]).
• Current hepatitis B infection (defined as positive for antibody to hepatitis B surface antigen (HBsAg) and/or positive for total hepatitis antibody to B core antigen [anti-HBc] with positive reflex HBV DNA).
• History of severe herpes infection.
• Presence of uncontrolled or New York Heart Association class III or IV congestive heart failure.
• Active severe lupus nephritis where, in the opinion of the Investigator, protocol-specified SOC is insufficient and use of a more aggressive therapeutic approach is indicated, such as adding IV cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol is indicated; or urine protein-creatinine ratio > 2.0 or severe chronic kidney disease (estimated glomerular filtration rate < 30 milliliters per minute per 1.73 meter square [mL/min/1.73 m^2]) calculated using the abbreviated modification of diet in renal disease equation.
• Any active skin conditions other than cutaneous lupus erythematosus (CLE) that may interfere with the study assessment of CLE such as but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE skin lupus manifestation or drug-induced lupus.
• History or current diagnosis of a clinically significant non-SLE-related vasculitis syndrome.
• Active neuropsychiatric SLE.
• Use of oral prednisone (or equivalent) above 20 mg/day.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Litifilimab Low Dose; Participants who are receiving background nonbiologic lupus SOC therapy will receive low dose of litifilimab, SC Q4W, up to Week 48 with an additional dose at Week 2.	Drug: Litifilimab; Administered as specified in the treatment arm.; Other Names: BIIB059
Placebo Comparator: Placebo; Participants who are receiving background nonbiologic lupus SOC therapy will receive litifilimab-matching placebo, SC Q4W, up to Week 48 with an additional dose at Week 2.	Drug: Placebo; Administered as specified in the treatment arm.
Experimental: Litifilimab High Dose; Participants who are receiving background nonbiologic lupus SOC therapy will receive high dose of litifilimab, subcutaneously (SC) every 4 weeks (Q4W), up to Week 48 with an additional dose at Week 2.	Drug: Litifilimab; Administered as specified in the treatment arm.; Other Names: BIIB059

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Systemic Lupus Erythematosus Responder Index of 4 (SRI-4) Response at Week 52	SRI-4 response is a composite endpoint defined by the following criteria: Reduction from baseline of ≥4 points in systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K).; No new organ system affected, as defined by no new organ system with British isles lupus assessment group-2004 (BILAG-2004) grade A and no more than 1 new organ system with BILAG-2004 grade B compared with Baseline.; No worsening from baseline in lupus disease activity as defined by <0.3-point increase on 3-point Physician's Global Assessment (PGA) - Visual Analog Scale (VAS).; No violation to protocol-specified medication rules.	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 4 Joints (Both Swollen and Tender) at Baseline Who Achieved a Joint-50 Response at Week 52	Joint-50 response is 50% reduction in total active joint count from baseline. An active joint is defined as a joint with pain and signs of inflammation (e.g., tenderness, swelling or effusion). A 28-joint assessment will be performed to determine the active joint count, which is defined as the sum of tender and swollen joint counts.	Week 52
Annualized Flare Rate Through Week 52	Annualized flare rate will be calculated as the total number of flares divided by the flare exposure time in days, and the ratio multiplied by 365.25.	Up to Week 52
Change from Baseline in Physician's Global Assessment (PGA) Visual Analog Scale (VAS) Score by Visit	The PGA is an Investigator-administered assessment used to quantify disease activity and is measured using an anchored VAS. The PGA asks the Investigator to assess the participant's current disease activity from a score of 0 (none) to 3 (severe), with the assessment made relative to the most severe state of SLE.	Up to Week 52
Time to Onset of SRI-4 Response Sustained Through Week 52	SRI-4 response is a composite endpoint defined by the following criteria: Reduction from baseline of ≥4 points in SLEDAI-2K.; No new organ system affected, as defined by no new organ system with British isles lupus assessment group-2004 (BILAG-2004) grade A and no more than 1 new organ system with BILAG-2004 grade B compared with Baseline.; No worsening from baseline in lupus disease activity as defined by <0.3-point increase on 3-point PGA -VAS.; No violation to protocol-specified medication rules.	Up to Week 52
Percentage of Participants Who Achieved SRI-4, -5, or -6 Response by Visit	SRI-4 response is a composite endpoint defined by the following criteria: Reduction from baseline of ≥4 points in SLEDAI-2K.; No new organ system affected, as defined by no new organ system with British isles lupus assessment group-2004 (BILAG-2004) grade A and no more than 1 new organ system with BILAG-2004 grade B compared with Baseline.; No worsening from baseline in lupus disease activity as defined by <0.3-point increase on 3-point PGA -VAS.; No violation to protocol-specified medication rules. The SRI-5 and SRI-6 are computed with a minimal five-point or six-point improvement in SLEDAI-2K being required, respectively.	Up to Week 52
Time to First British Isles Lupus Activity Group-2004 (BILAG-2004) Severe Flare by Visit	BILAG-2004 severe flare is defined as an A score for items recorded as worse or new. BILAG-2004 is evaluated by scoring each item of a list of signs and symptoms given as 4 = new; 3 = worse; 2 = same; 1 = improving; 0 = not present; and ND = not done.	Up to Week 52
Time to First Severe Flare as defined by the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index Flare Index (SFI)	SFI severe flare is defined any of the following: change in SLEDAI instrument score to >12; or new or worse: central nervous system SLE; vasculitis; nephritis; myositis; platelets <60,000 per milliliter (/mL); or hemolytic anemia with hemoglobin <7 grams per deciliter (g/dL) or decrease in hemoglobin >3 g/dL and requiring: doubling prednisone dose; or increase to >0.5 milligrams per kilogram per day (mg/kg/day) or hospitalization; or increase in prednisone dose to >0.5 mg/kg/day; or new requirement for cyclophosphamide, azathioprine, methotrexate, or mycophenolate for SLE activity; or hospitalization for SLE activity; or increase in PGA score to >2.5.	Up to Week 52
Percentage of Participants With Baseline OCS ≥10 mg/day Who Achieved ≤7.5 mg/day at Week 52		Week 52
Change from Baseline in Lupus-Specific Health-Related Quality-of-Life Questionnaire (LupusQoL) Score	The LupusQoL is a participant-reported, lupus-specific, Health-Related Quality-of-Life Questionnaire (HRQoL) consisting of 34 items grouped in 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4 = never, 3 = occasionally, 2 = a good bit of the time, 1 = most of the time, and 0 = all the time. A LupusQoL score for each domain will be reported on a 0 to 100 scale, with greater values indicating better HRQoL.	Up to Week 52
Change From Baseline in Short Form Health Survey-36 (SF-36) Score	The SF-36 determines participant's overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement.	Up to Week 52
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score	The FACIT-Fatigue is a participant-administered HRQoL questionnaire that evaluates participant's fatigue in the 5 broad categories: physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns. The level of fatigue is measured by questions assessed on a 5-point scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The responses for each item are added to obtain a total score which ranges from 0 to 52, with a higher score indicating less fatigue.	Up to Week 52
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Score	The PHQ-9 is a participant-administered HRQoL questionnaire to screen for the presence and severity of depression. The PHQ-9 is a participant-reported outcome (PRO) that is used to measure depression in adults. It contains 9 questions. The PHQ-9 yields an overall severity score that can range from 0 to 27 with the following severity scores: 0-4 = none; 5-9 = mild; 10-14 = moderate; 15-19 = moderate-to-severe; and 20-27 = severe.	Up to Week 52
Change From Baseline in Work Productivity and Activity Impairment (WPAI): Lupus Score	WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. Each score ranges from 0 to 100, with higher numbers indicating greater impairment and less productivity	Up to Week 52
Percentage of Time Spent in Lupus Low Disease Activity State (LLDAS)	LLDAS is a composite endpoint defined as: SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and; No new features of lupus disease activity compared with the previous assessment; and; Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) PGA ≤ 1; and; Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and; Standard maintenance doses of immunosuppressive drugs and approved biological agents.	Up to Week 52
Percentage of Participants With Sustained LLDAS as Defined by the Number of Participants With ≥ 3, ≥ 5, and ≥ 7 Consecutive Visits in LLDAS up to and Including Week 52	LLDAS is a composite endpoint defined as: SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and; No new features of lupus disease activity compared with the previous assessment; and; SELENA-SLEDAI PGA ≤ 1; and; Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and; Standard maintenance doses of immunosuppressive drugs and approved biological agents.	Up to Week 52
Percentage of Participants who Achieved LLDAS at Week 52	LLDAS is a composite endpoint defined as: SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and; No new features of lupus disease activity compared with the previous assessment; and; SELENA-SLEDAI PGA ≤ 1; and; Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and; Standard maintenance doses of immunosuppressive drugs and approved biological agents.	Week 52
Percentage of Participants Who Achieved a British Isles Lupus Activity Group (BILAG) - Based Combined Lupus Assessment (BICLA) Response at Week 52	The BILAG disease activity index evaluates SLE activity in number of organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows, BILAG A: severe disease activity; BILAG B: moderate disease activity; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved. BICLA is a composite endpoint defined as BILAG-2004 improvement, defined as all BILAG-2004 grade A at Baseline improved to grade B, C, or D, and all BILAG-2004 grade B at baseline improved to grade C or D, no BILAG-2004 worsening in other BILAG-2004 organ systems such that there are no new BILAG-2004 grade A or greater than 1 new BILAG-2004 grade B, no worsening in the SLEDAI-2K total score compared with Baseline, no worsening from Baseline in lupus disease activity defined by < 0.3-point increase on 3-point PGA-VAS and no violation to protocol-specified medication rules.	Week 52
Percentage of Participants With Joint-50 Response by Visit	Joint-50 response is 50% reduction in total active joint count from baseline. An active joint is defined as a joint with pain and signs of inflammation (e.g., tenderness, swelling or effusion). A 28-joint assessment will be performed to determine the active joint count, which is defined as the sum of tender and swollen joint counts.	Up to Week 52
Percentage of Participants With Baseline CLASI-A Score ≥10 Who Achieved a CLASI-20, -50, -70, or -90 Response by Visit	Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity (CLASI-A) score is used to evaluate lupus skin manifestations. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represent disease severity of mild, moderate, and severe, respectively. CLASI-20, -50, -70 and -90 represent 20%, 50%, 70% or 90% improvement from baseline in CLASI-A score, respectively.	Up to Week 52
Percentage of Participants who Achieved SLEDAI-2K Improvement at Week 52	The SLEDAI-2K is a reliable, valid, simple, 1-page activity index that measures disease activity and records features of active lupus as present or not. It uses a weighted checklist to assign a numeric score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 28 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms), where higher scores represent increased disease activity. SLEDAI-2K improvement is defined as a reduction from Baseline of ≥ 4 points in SLEDAI-2K score.	Week 52
Percentage of Participants who Achieved no Worsening of BILAG at Week 52	The BILAG disease activity index evaluates SLE activity in number of organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows, BILAG A: severe disease activity; BILAG B: moderate disease activity; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved. No worsening of BILAG is defined as no new organ system affected, as defined by no new organ system with BILAG-2004 grade A and no more than 1 new organ system with BILAG-2004 grade B compared with Baseline.	Week 52
Percentage of Participants who Achieved BILAG Improvement at Week 52	The BILAG disease activity index evaluates SLE activity in number of organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows, BILAG A: severe disease activity; BILAG B: moderate disease activity; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved. BILAG-2004 improvement, defined as all BILAG-2004 grade A at Baseline improved to grade B, C, or D, and all BILAG-2004 grade B at Baseline improved to grade C or D. BILAG-2004 improvement, defined as all BILAG-2004 grade A at Baseline improved to grade B, C, or D, and all BILAG-2004 grade B at Baseline improved to grade C or D. BILAG-2004 improvement, defined as all BILAG-2004 grade A at Baseline improved to grade B, C, or D, and all BILAG-2004 grade B at Baseline improved to grade C or D.	Week 52
Percentage of Participants With OCS ≥ 7.5 mg/day at Baseline With OCS Reduction to ≤ 7.5 mg/day at Week 52		Week 52
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A TEAE is an AE that started or worsened in severity after the first dose of study treatment through 28 days after the last dose of study treatment or end of study (EOS) date, whichever comes earlier. An SAE is any untoward medical occurrence that at any dose results in death (a life-threatening event), in the view of the investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect, or is a medically important event.	Up to Week 52
Number of Participants With Antibodies to Litifilimab		Up to Week 52
Percentage of Participants With Oral Corticosteroid(s) (OCS) ≥10 milligrams per day (mg/day) at Baseline With OCS Reduction to ≤7.5 mg/day at Week 40, Which Is Sustained Through Week 52 with No Disease Worsening from Week 40 to Week 52	No worsening of the disease is defined as no new BILAG-2004 grade A or less than 2 new BILAG-2004 grade B since the last visit during the Week 40 to Week 52.	Week 40 to Week 52
Percentage of Participants With a CLASI-A score ≥10 at Baseline Who Achieved a 50% Improvement From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity Score (CLASI-50) Response at Week 24	Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity (CLASI-A) score is used to evaluate lupus skin manifestations. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represent disease severity of mild, moderate, and severe, respectively. CLASI-50 is 50% of improvement from baseline in CLASI-A.	Week 24
Percentage of Participants Who Achieved a BILAG-BICLA Response by Visit	The BILAG disease activity index evaluates SLE activity in number of organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows, BILAG A: severe disease activity; BILAG B: moderate disease activity; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved. BICLA is a composite endpoint defined as BILAG-2004 improvement, defined as all BILAG-2004 grade A at Baseline improved to grade B, C, or D, and all BILAG-2004 grade B at baseline improved to grade C or D, no BILAG-2004 worsening in other BILAG-2004 organ systems such that there are no new BILAG-2004 grade A or greater than 1 new BILAG-2004 grade B, no worsening in the SLEDAI-2K total score compared with Baseline, no worsening from Baseline in lupus disease activity defined by < 0.3-point increase on 3-point PGA-VAS and no violation to protocol-specified medication rules.	Up to Week 52
Percentage of Participants With Baseline CLASI-A Score ≥10 Who Achieved a CLASI-A Score of ≤ 1 by Visit	Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity (CLASI-A) score is used to evaluate lupus skin manifestations. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represent disease severity of mild, moderate, and severe, respectively. CLASI-A ≤1 represent the absolute score ≤1 in CLASI-A by visit.	Up to Week 52
Percentage of Participants With Severe Flares Through Week 52	A SFI severe flare is defined as any of the following: Change in SLEDAI instrument score to > 12.; New or worse: central nervous system SLE; vasculitis; nephritis; myositis; platelets < 60,000/mL; or hemolytic anemia with hemoglobin < 7 g/dL or decrease in hemoglobin >3 g/dL AND requiring: doubling prednisone dose, increase to > 0.5 mg/kg/day or hospitalization.; Increase in prednisone dose to > 0.5 mg/kg/day.; New requirement for cyclophosphamide, azathioprine, methotrexate, or mycophenolate for SLE activity.; Hospitalization for SLE activity.; Increase in PGA score to > 2.5.	Up to Week 52
Percentage of Participants who Achieved no Worsening of PGA-VAS at Week 52	The PGA is an investigator-administered assessment used to quantify disease activity and is measured using an anchored VAS. PGA asks the investigator to assess the participant's current disease activity from a score of 0 (none) to 3 (severe), with the assessment made relative to the most severe state of SLE. No worsening from Baseline in lupus disease activity is defined by < 0.3-point increase on 3-point PGA-VAS. No worsening from Baseline in lupus disease activity as defined by < 0.3-point increase on 3-point PGA-VAS.	Week 52
Percentage of Participants who Achieved no Worsening of SLEDAI-2K at Week 52	The SLEDAI-2K uses a weighted checklist to assign a numeric score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 28 (+2) days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms present) to 105 points (presence of all defined symptoms). No worsening of SLEDAI-2K is defined as no increase in the SLEDAI-2K total score from baseline.	Week 52
Percentage of Participants With OCS ≥ 10 mg/day at Baseline With OCS Reduction to ≤ 5 mg/day at Week 40, Which is Sustained Through Week 52 With no Disease Worsening From Week 40 to Week 52	No worsening of the disease is defined as no new BILAG-2004 grade A or less than 2 new BILAG-2004 grade B since the last visit between Week 40 and Week 52.	Week 40 up to Week 52

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Publications and helpful links

Helpful Links

• Click here to learn more about this trial, visit our study website

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): March 16, 2027

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Lupus; SLE; CLE
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: 230LE303; 2023-505695-30 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No