A Study to Evaluate the Continuous Safety and Efficacy of Litifilimab (BIIB059) in Adults With Active Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) Clinical Trial

— EMERALD  

Official title:

A Multicenter, Randomized, Dose-Blind, Phase 3 Long-Term Extension Study to Evaluate Continuous Safety and Efficacy of Litifilimab (BIIB059) in Adult Participants With Active Systemic Lupus Erythematosus

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05352919
• Other study ID #: 230LE306
• Secondary ID: 2021-006378-22
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: June 10, 2022
• Est. completion date: March 13, 2029

Study information

• Verified date: June 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the long-term safety and tolerability of litifilimab in participants with active systemic lupus erythematosus (SLE).

The secondary objectives of this study are to evaluate the long-term effect of litifilimab on disease activity in participants with SLE, to evaluate the long-term effect of litifilimab in participants with SLE in maintaining low disease activity, to evaluate the effect of litifilimab in participants with active SLE in preventing irreversible organ damage, to assess long-term use of oral corticosteroid (OCS) with participants receiving litifilimab treatment, to assess the impact of litifilimab on participant-reported Health-Related Quality-of-Life Questionnaire (HRQoL), symptoms, and impacts of SLE, to evaluate long-term effect of litifilimab on laboratory parameters, and to evaluate immunogenicity of litifilimab.

Description:

This is an extension study for all participants who completed study 230LE303 (NCT04895241) and 230LE304 (NCT04961567) (parent phase 3 studies) through Week 52 and did not discontinue litifilimab or placebo. Eligible participants from parent phase 3 studies will be followed for up to 180 weeks.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 864
• Est. completion date: March 13, 2029
• Est. primary completion date: March 13, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Participants who completed 1 of the 52-week of the double-blind placebo-controlled, parent Phase 3 studies (230LE303 (NCT04895241) and 230LE304 (NCT04961567)) on study treatments with either litifilimab or placebo to Week 48 and attended the last study assessment visit at Week 52

Key Exclusion Criteria:

• Early parent Phase 3 studies treatment terminators (participants who discontinued study treatment before Week 52)

• Early parent Phase 3 studies terminators (participants who withdrew from study participation and did not complete the 52 week treatment period)

• Participants who developed moderate-to-severe worsening of organ-specific lupus manifestations that would require a change in antimalarials and/or immunosuppressive therapy (initiation of new treatment or increase in dose above the allowed maximum dose)

• Use of other investigational drugs or off-label drugs used to treat SLE, cutaneous lupus, or lupus nephritis during the parent Phase 3 studies

NOTE: Other inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus (SLE)

Intervention

Drug:
• Litifilimab
Administered as specified in the treatment arm.
• Litifilimab-matching placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de La Plata	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Quilmes	Buenos Aires
Argentina	STAT Research S.A.	Ciudad Autonoma Buenos Aires
Argentina	Centro de Investigaciones Medicas Mar del Plata	Mar del Plata	Buenos Aires
Argentina	CER San Juan Centro Polivalente de Asistencia e Inv. Clinica	San Juan
Argentina	Centro Dermatologico Schejtman	San Miguel	Buenos Aires
Argentina	Centro de Investigaciones Medicas Tucuman	San Miguel de Tucuman	Tucuman
Argentina	Investigaciones Clinicas Tucuman	San Miguel de Tucuman	Tucuman
Belgium	Centre Hospitalier Universitaire de Liege	Liège
Brazil	CMiP - Centro Mineiro de Pesquisa	Juiz de Fora	Minas Gerais
Brazil	CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos	São Paulo	Sao Paulo
Bulgaria	MC Artmed OOD	Plovdiv
Bulgaria	UMHAT-Plovdiv AD	Plovdiv
Bulgaria	DCC 1 - Ruse, EOOD	Ruse
Bulgaria	DCC 'Alexandrovska', EOOD	Sofia
Bulgaria	DCC Focus 5 - MEOH OOD	Sofia
Bulgaria	Military Medical Academy - MHAT - Sofia	Sofia
Chile	BioMedica Research Group	Santiago
Chile	Centro Medico Prosalud	Santiago
Chile	CTR Estudios	Santiago
Chile	Enroll Spa	Santiago
China	The First Hospital of Jilin University	Changchun
China	The First Affiliated Hospital of Ningbo University	Ningbo	Zhejiang
China	ZhuZhou Central Hospital	ZhuZhou	Hunan
Colombia	Centro de Investigacion Medico Asistencial S.A.S	Barranquilla
Colombia	Clínica de la Costa S.A.S	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialidades Medicas CIREEM S.A.S.	Bogotá
Colombia	Servimed S.A.S.	Bucaramanga
Colombia	Preventive Care Ltda	Chia
Colombia	Healthy Medical Center	Zipaquirá
Czechia	Revmatologie s.r.o.	Brno
Czechia	Fakultni nemocnice Olomouc	Olomouc
France	CHU Clermont Ferrand - Hopital Gabriel Montpied	Clermont-Ferrand cedex 1	Drôme
Hungary	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Bekes Varmegyei Kozponti Korhaz	Gyula
Hungary	Vital Medical Center	Veszprem
Israel	Meir Medical Center	Kfar- Saba
Israel	Tel Aviv Sourasky Medical Center Pt	Tel Aviv
Japan	NHO Chibahigashi National Hospital	Chiba-shi	Chiba-Ken
Japan	NHO Kyushu Medical Center	Fukuoka-shi	Fukuoka-Ken
Japan	Japanese Red Cross Society Himeji Hospital	Himeji-shi	Hyogo-Ken
Japan	Hiroshima University Hospital	Hiroshima-shi	Hiroshima-Ken
Japan	Nihon University Itabashi Hospital	Itabashi-ku	Tokyo-To
Japan	Toho University Ohashi Medical Center	Meguro-ku	Tokyo-To
Japan	JCHO Chukyo Hospital	Nagoya-shi	Aichi-Ken
Japan	Kindai University Hospital	Osakasayama-shi	Osaka-Fu
Japan	Tonan Hospital	Sapporo-shi	Hokkaido
Japan	Center Hospital of the National Center for Global Health and Medicine	Shinjuku-ku	Tokyo-To
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon	Gyeonggi-do
Mexico	Investigacion y Biomedicina de Chihuahua, S.C.	Chihuahua
Mexico	Clinstile, S.A. de C.V.	Ciudad de México	Distrito Federal
Mexico	Consultorio Privado Dr. Miguel Cortes Hernandez	Cuernavaca	Morelos
Mexico	Centro de Investigacion y Atencion Integral Durango CIAID	Durango
Mexico	Clinica de Investigacion en Reumatologia y Obesidad S.C.	Guadalajara	Jalisco
Mexico	Medical Care & Research SA de CV	Merida	Yucatán
Mexico	Centro de Investigacion Clínica GRAMEL S.C	Mexico	Distrito Federal
Philippines	Davao Doctors Hospital	Davao City	Davao
Philippines	Mary Mediatrix Medical Center	Lipa City	Batangas
Philippines	Far Eastern University - Dr. Nicanor Reyes Medical Foundation	Quezon City	Metro Manila
Poland	Nova Reuma Domyslawska i Rusilowicz, Spólka Partnerska Lekarza Reumatologa i Fizjoterapeuty	Bialystok
Poland	Szpital Uniwersytecki nr 2 im.dr J. Biziela	Bydgoszcz
Poland	Nzoz Bif-Med	Bytom
Poland	Pratia MCM Krakow	Krakow
Poland	Centrum Badawcze Panaceum Agnieszka Brzezicka, Magdalena Lenkiewicz Sp. z o.o.	Malbork
Poland	MICS Centrum Medyczne Warszawa	Warszawa
Romania	S.C Centrul Medical de Diagnostic si Tratament Ambulator Neomed S.R.L	Brasov
Romania	S C Delta Health Care SRL	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Cluj Napoca	Cluj-Napoca
Serbia	Institute of Rheumatology	Belgrade
Serbia	University Clinical Center of Serbia	Belgrade
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Marques de Valdecilla	Santander	Castellón
Spain	Hospital Quironsalud Infanta Luisa	Sevilla
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
United Kingdom	Doncaster Royal Infirmary	Doncaster	South Yorkshire
United Kingdom	Guy's Hospital	London	Greater London
United States	Arthritis & Rheumatic Disease Specialties	Aventura	Florida
United States	Wallace Rheumatic Study Center	Beverly Hills	California
United States	DJL Clinical Research, PLLC	Charlotte	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Clinical Research of West Florida - Corporate	Clearwater	Florida
United States	Precision Comprehensive Clinical Research Solution	Colleyville	Texas
United States	Precision Comprehensive Clinical Research Solutions	Colleyville	Texas
United States	Omega Research Consultants	DeBary	Florida
United States	AA MRC LLC Ahmed Arif Medical Research Center	Flint	Michigan
United States	Arthritis Center of North Georgia	Gainesville	Georgia
United States	Accurate Clinical Research, Inc.	Humble	Texas
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Life Clinical Trials	Margate	Florida
United States	Ramesh C Gupta, MD	Memphis	Tennessee
United States	Paramount Medical Research & Consulting, LLC	Middleburg Heights	Ohio
United States	Providence Facey Medical Foundation	Mission Hills	California
United States	Saint Louis Rheumatology	Saint Louis	Missouri
United States	Sun Research Institute, LLC	San Antonio	Texas
United States	Swedish Medical Center	Seattle	Washington
United States	Accurate Clinical Research	Stafford	Texas
United States	AdventHealth Medical Group	Tampa	Florida
United States	Advanced Rheumatology of Houston	The Woodlands	Texas
United States	Inland Rheumatology Clinical Trials, Inc.	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Bulgaria,  Chile,  China,  Colombia,  Czechia,  France,  Hungary,  Israel,  Japan,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Romania,  Serbia,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. 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.	Up to Week 180
Primary	Number of Participants with Serious Adverse Events (SAEs)	An SAE is any untoward medical occurrence that at any dose results in death, in the view of the Investigator, places the participant at immediate risk of death (a life threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, and is a medically important event.	Up to Week 180
Secondary	Percentage of Participants who Achieved an Systemic Lupus Erythematosus Responder Index (SRI)-4 Response	SRI-4 is a composite endpoint defined as the following: A reduction from baseline of =4 points in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score.; No new organ system affected, as defined by no new British Isles Lupus Activity Group-2004 (BILAG-2004 grade A) and no more than 1 new BILAG 2004 grade B versus previous visit.; 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 of protocol-specified medication rules	Up to Week 180
Secondary	Percentage of Participants who Achieved a Joint-50 Response	Joint-50 response is a 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 180
Secondary	Percentage of Participants who Achieved Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50, CLASI-70, and CLASI-90 Response	CLASI score is used to evaluate lupus skin manifestations. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Scores for each area are assigned based on the most severe lesion within the area of interest. 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. CLASI-70 is 70% of improvement from baseline in CLASI-A and CLASI-90 is 90% of improvement from baseline in CLASI-A.	Up to Week 180
Secondary	Percentage of Participants who Achieved a British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) Response	BICLA is a composite endpoint defined as the following: BILAG-2004 improvement, defined as all of BILAG-2004 Grade A at Baseline improved to B, C, or D and all of BILAG-2004 Grade B at Baseline improved to 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 to baseline.; No worsening from baseline in lupus disease activity defined by a <0.3-point increase on a 3-point PGA VAS.; No violation of protocol-specified medication rules.	Up to Week 180
Secondary	Annualized Severe Safety of Estrogens in Systemic Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index Flare Index (SFI) Flare Rate	A 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 grams per deciliter (g/dL) or decrease in hemoglobin >3 g/dL and requiring: doubling prednisone dose, increase to >0.5 milligrams per kilograms per day (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 156
Secondary	Percentage of Time Spent in Lupus Low Disease Activity State (LLDAS)	LLDAS is a composite endpoint defined as the following: i. SLEDAI-2K score = 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA = 1; and iv. Current prednisone (or equivalent) dose = 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents.; "No new features" is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. "Standard maintenance doses" include drugs limited to those allowed per protocol.	Up to Week 180
Secondary	Percentage of Participants With Sustained LLDAS	LLDAS is a composite endpoint defined as the following: i. SLEDAI-2K score = 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA = 1; and iv. Current prednisone (or equivalent) dose = 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents.; "No new features" is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. "Standard maintenance doses" include drugs limited to those allowed per protocol.	Up to Week 180
Secondary	Duration of Sustained LLDAS as Defined by the Number of Visits in LLDAS	LLDAS is a composite endpoint defined as the following: i. SLEDAI-2K score = 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA = 1; and iv. Current prednisone (or equivalent) dose = 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents.; "No new features" is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. "Standard maintenance doses" include drugs limited to those allowed per protocol.	Up to Week 180
Secondary	Annual Change From Baseline Value From the Parent Phase 3 Studies in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) Score	SDI score is used to assess the accumulated damage in participants with SLE. It assess 12 organ systems and records damage in participants with lupus, regardless of its cause. Damage could be due to previous disease activity, medication, or intercurrent illness (such as surgery or cancer). To distinguish between active inflammation and damage, an item must be present for at least 6 months. It is assumed that persistent inflammation (for at least 6 months) would result in tissue injury and hence damage. SDI is evaluated on a scale 0-47 with higher score indicating higher damage.	Up to Week 156
Secondary	Cumulative Exposure to OCS Over Time		Up to Week 156
Secondary	Percentage of Participants With OCS =7.5 mg		Up to Week 156
Secondary	Percentage of Participants With OCS =5 mg		Up to Week 156
Secondary	Change From Baseline in Lupus-Specific Health-Related Quality-Of-Life (LupusQoL) Score	The LupusQoL is a participant-reported, lupus-specific, HRQoL questionnaire 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 156
Secondary	Change From Baseline in Short Form Health Survey-36 (SF-36) (Acute Version) Score	The SF-36 is a 36-item scale which assesses HRQoL in 8 domains: limitations in physical activities due to health problems, limitations in social activities due to physical or emotional problems, limitations in usual role activities due to physical health problems, bodily pain, general mental health (psychological distress and well-being), limitations in usual role activities due to emotional problems, vitality (energy and fatigue), general health perceptions. The SF-36 (Acute Version) form asks for participants to reply to questions (items) according to how they have felt over a specifically defined period of time. 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 where higher scores indicate best health. Scores on each item are summed and averaged (range: 0=worse health to 100=best possible health).	Up to Week 156
Secondary	Change From Baseline in European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L)	The EQ-5D is a standardized generic measure of health status developed by the European Quality of Life Group. This study uses the EQ-5D-3L version of the instrument. This instrument consists of 2 sections. The first section comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. All dimensions are measured on a 3-point scale, 1: No problems; 2: Some problems; 3: Extreme problems. The second section comprises the Visual Analogue Scale, which records the respondent's self-rated health on a vertical scale ranging from 0 to 100, lower scores indicate the worst possible health state.	Up to Week 156
Secondary	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score	The FACIT-Fatigue is a participant-administered HRQoL questionnaire that evaluates participant's fatigue in 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 156
Secondary	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, with a 2 week recall period. 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 156
Secondary	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 156
Secondary	Change from Baseline in Patient Global Assessment (PtGA) Score	The PtGA is participant-administered, single-item question evaluating the impact of health and illness, with responses ranging from very poor to very well on a 100 mm VAS. The participant will consider the previous week when addressing this question.	Up to Week 156
Secondary	Number of Participants with Clinically Relevant Abnormalities in Standard Laboratory Parameters	Standard laboratory parameters will include hematology, blood chemistry, urinalysis, and coagulation.	Up to Week 180
Secondary	Number of Participants with Clinically Relevant Abnormalities in Electrocardiogram (ECG) Results		Up to Week 156
Secondary	Number of Participants with Antibodies to Litifilimab		Up to Week 180