Clinical trial NCT03616964: A Study of Baricitinib in Participants With Systemic Lupus Erythematosus (SLE-BRAVE II)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients With Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Keywords: SLE
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Incyte Corporation
First posted: 2018-08-06
Enrollment: 778
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The reason for this study is to see how effective and safe the study drug known as baricitinib is in participants with systemic lupus erythematosus (SLE).


Eligibility criteria: Inclusion Criteria:

* Have a clinical diagnosis of SLE at least 24 weeks prior to screening.
* Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 American College of Rheumatology (ACR) criteria for classification of SLE prior to randomization.
* Have a positive antinuclear antibody (ANA) (titer ≥1:80) and/or a positive anti-double-stranded deoxyribonucleic acid (dsDNA), and/or a positive anti-Smith (anti-Sm) as assessed by a central laboratory during screening.
* Have a total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥6 during screening.
* Have a clinical SLEDAI-2K score ≥4 at randomization.
* Have at least 1 British Isles Lupus Assessment Group (BILAG) A score or 2 BILAG B scores during screening.
* Are receiving at least one of the following standard of care medications for SLE:

  * A single antimalarial at a stable dose for at least 8 weeks prior to screening
  * A single immunosuppressant at a stable dose for at least 8 weeks prior to screening
  * An oral corticosteroid, initiated at least 4 weeks prior to screening, at a stable dose ≤40 milligrams/day prednisone (or equivalent) for at least 2 weeks prior to screening. If the participant is not receiving an antimalarial or immunosuppressant, the dose of corticosteroid must be ≥7.5 milligrams/day prednisone (or equivalent)

Exclusion Criteria:

* Have severe active lupus nephritis.
* Have active central nervous system (CNS) lupus.
* Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
* Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection.
* Have received cyclophosphamide (or any other cytotoxic agent) within 12 weeks prior to screening.

Primary outcomes:
measure: Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (4 mg Baricitinib)
timeFrame: Week 52
Secondary outcomes:
measure: Percentage of Participants Achieving SRI-4 Response (2 mg Baricitinib)
timeFrame: Week 52
measure: Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS)
timeFrame: Week 52
measure: Time to First Severe Flare
timeFrame: Baseline to Week 52
measure: Percentage of Participants Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 in Participants Receiving Greater Than 7.5 mg/Day at Baseline
timeFrame: Baseline, Week 40 through Week 52
measure: Change From Baseline in Worst Pain Numeric Rating Scale (NRS)
timeFrame: Baseline, Week 52
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score
timeFrame: Baseline, Week 52
measure: Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Total Activity Score ≥10 at Baseline With ≥50% Reduction in CLASI Total Activity Score
timeFrame: Week 52
measure: Change From Baseline in Tender Joint Count
timeFrame: Baseline, Week 52
measure: Change From Baseline in Swollen Joint Count
timeFrame: Baseline, Week 52
measure: Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve for Dosing Interval of Baricitinib at Steady State (AUCtau,ss)
timeFrame: Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose
measure: Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss)
timeFrame: Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: University of Arizona Arthritis Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Research
state: Arizona
city: Tucson
country: United States
facility: Arizona Arthritis & Rheumatology Associates, P. C.
state: Arizona
city: Beverly Hills
country: United States
facility: Wallace Rheumatic Studies Center
state: California
city: Covina
country: United States
facility: Medvin Clinical Research - Weidmann
state: California
city: Tustin
country: United States
facility: Office: Dr Robin K Dore
state: California
city: Upland
country: United States
facility: Inland Rheumatology & Osteoporosis Medical Group
state: California
city: Denver
country: United States
facility: Denver Arthritis Clinic - Lowry
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc. (Clearwater)
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology & Immunology Specialists
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Tampa
country: United States
facility: Tampa Medical Group, P.A.
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Lawrenceville
country: United States
facility: North Georgia Rheumatology, PC
state: Georgia
city: Lexington
country: United States
facility: Arthritis Center of Lexington
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Lansing
country: United States
facility: Advanced Rheumatology, PC
state: Michigan
city: Kalispell
country: United States
facility: Glacier View Research Institute - Endocrinology
state: Montana
city: Las Vegas
country: United States
facility: Innovative Health Research
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Las Cruces
country: United States
facility: Arthritis and Osteoporosis Associates of New Mexico
state: New Mexico
city: Canton
country: United States
facility: St. Lawrence Health System
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Joint and Muscle Medical Care
state: North Carolina
city: Charlotte
country: United States
facility: Box Arthritis & Rheumatology of the Carolinas, PLLC
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Rheumatic Disease Study Group
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Wyomissing
country: United States
facility: Clinical Research Center of Reading,LLC
state: Pennsylvania
city: Summerville
country: United States
facility: Articularis Healthcare d/b/a/ Low Country Rheumatology, PA
state: South Carolina
city: Crossville
country: United States
facility: Eagle Medical
state: Tennessee
city: Colleyville
country: United States
facility: Dr. Dhiman Basu Private Practice
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: The Woodlands
country: United States
facility: Advanced Rheumatology of Houston
state: Texas
city: Webster
country: United States
facility: Clear Lake Specialties
state: Texas
city: Arlington
country: United States
facility: Arthritis Clinic of Northern VA, P.C.
state: Virginia
city: Danville
country: United States
facility: Spectrum Medical Inc.
state: Virginia
city: Caba
country: Argentina
facility: Aprillus Asistencia e Investigacion - Servicio de neurologia
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: DOM Centro de Reumatologia
state: Buenos Aires
city: La Plata
country: Argentina
facility: Framingham Centro Medico
state: Buenos Aires
city: Quilmes
country: Argentina
facility: CER Instituto Medico
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clinicas Quilmes
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Comite de Etica en Investigacion - CEMIC
state: Ciudad Autonoma De Buenos Aire
city: Caba
country: Argentina
facility: Clinica Adventista Belgrano
state: Ciudad Autónoma De Buenos Aire
city: Rosario
country: Argentina
facility: Sanatorio Británico
state: Santa Fe
city: SAN M. DE Tucuman
country: Argentina
facility: Centro Medico Privado de Reumatologia
state: Tucumán
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Sanatorio Guemes Cardiocirugia
city: Mendoza
country: Argentina
facility: IR Medical Center S.A. Instituto de Reumatologia
city: Valdivia
country: Chile
facility: Clinical Research Chile SpA
state: Los Ríos
city: Providencia
country: Chile
facility: Enroll SpA
state: Región Metropolitana De Santia
city: Osorno
country: Chile
facility: Clinica Alemana de Osorno
city: Santiago
country: Chile
facility: Sociedad Medica Del Aparato Locomotor SA
city: Santiago
country: Chile
facility: Prosalud y cia. Ltda.
city: Vina del Mar
country: Chile
facility: ReumaCen Centro Reumatologico Integral
city: Medellin
country: Colombia
facility: HPTU-El Hospital con alma Pablo Tobon Uribe
state: Antioquia
city: Barranquilla
country: Colombia
facility: Clinica de la Costa
state: Atlantico
city: Barranquilla
country: Colombia
facility: Circaribe SAS
state: Atlántico
city: Bogota
country: Colombia
facility: Idearg S.A.S.
state: Cundinamarca
city: Bogotá
country: Colombia
facility: Centro Integral de Reumatologia e Inmunologia
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Servimed S.A.S.
state: Santander
city: Cali
country: Colombia
facility: Centro de Medicina Interna
state: Valle Del Cauca
city: Chia
country: Colombia
facility: Preventive Care Ltdac
city: Brest Cedex
country: France
facility: CHRU Brest - Hopital Cavale Blanche
state: Finistère
city: Pessac
country: France
facility: Centre hospitalier universitaire de Haut Leveque
state: Gironde
city: Montpellier
country: France
facility: CHU Montpellier Lapeyronie Hospital
state: Hérault
city: Bordeaux
country: France
facility: Centre hospitalier universitaire Pellegrin
city: Marseille
country: France
facility: Hopital Européen
city: Hyderabad
country: India
facility: Krishna Institute of Medical Science
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Panchshil Hospital
state: Gujarat
city: Ahmedabad
country: India
facility: CIMS Hospital Private Limited
state: Gujarat
city: Ahmedabad
country: India
facility: NHL Municipal Medical College & VS General Hospital
state: Gujarat
city: Rajkot
country: India
facility: Shree Giriraj Hospital
state: Gujarat
city: Surat
country: India
facility: Nirmal Hospital Private Limited
state: Gujarat
city: Vadodara
country: India
facility: Sterling Hospital
state: Gujarat
city: Bangalore
country: India
facility: St. John Medical College & Hospital
state: Karnataka
city: Bangalore
country: India
facility: ChanRe Rheumatology And Immunology Center And Research
state: Karnataka
city: Hubli
country: India
facility: Sushruta Multispecialty Hospital & Research Center Pvt Ltd
state: Karnataka
city: Madhav Nagar, Manipal
country: India
facility: Kasturba Medical College Hospital, Mangalore
state: Karnataka
city: Nagpur
country: India
facility: Jasleen Hospital
state: Maharashtra
city: Nashik
country: India
facility: Synexus Affiliate - Sujata Birla Hospital & Medical Research Center
state: Maharashtra
city: Jaipur
country: India
facility: Fortis Escorts Hospital
state: Rajasthan
city: Modena
country: Italy
facility: Azienda Ospedaliera Universitaria
state: MO
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
state: Toscana
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: Milano
country: Italy
facility: Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I
city: Udine
country: Italy
facility: Azienda Ospedaliera Santa Maria Della Misericordia
city: Kitakyushu
country: Japan
facility: University of Occupational and Enviromental Health
state: Fukuoka
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima-ken
city: Asahikawa
country: Japan
facility: National Hospital Organization Asahikawa Medical Center
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Himeji
country: Japan
facility: Jp Red Cross Society Himeji Hp
state: Hyogo
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kita-gun
country: Japan
facility: Kagawa University Hospital
state: Kagawa
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Chuo-Ku
country: Japan
facility: St. Lukes International Hospital
state: Tokyo
city: Meguro-ku
country: Japan
facility: Toho University Ohashi Med C
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Showa University Hospital
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Fukuoka
country: Japan
facility: Hamanomachi Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Kyung Pook National University Hospital
state: Korea
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
state: Korea
city: Seoul
country: Korea, Republic of
facility: Hanyang University Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul-teukbyeolsi [Seoul]
city: Seocho-Gu
country: Korea, Republic of
facility: The Catholic University of Korea-Seoul St. Mary's Hospital
state: Seoul
city: Lipa
country: Philippines
facility: Mary Mediatrix Medical Center
state: Batangas
city: Cebu City
country: Philippines
facility: Cebu Doctors Hospital
state: Cebu
city: Davao
country: Philippines
facility: Southern Philippines Medical Center
state: Davao Del Norte
city: Angeles City
country: Philippines
facility: Angeles University Foundation and Medical Center
state: Pampanga
city: Cebu City
country: Philippines
facility: Chong Hua Medical Arts Center
city: Makati City
country: Philippines
facility: Makati Medical Center
city: Quenzon City
country: Philippines
facility: St. Luke's Medical Center
city: Wroclaw
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Biogenes Sp. z o.o.
state: Dolnoslaskie
city: Nowa Sol
country: Poland
facility: Twoja Przychodnia Centrum Medyczne Nowa Sol
state: Lubuskie
city: Warszawa
country: Poland
facility: Medycyna Kliniczna
state: Mazowieckie
city: Warszawa
country: Poland
facility: Reumatika - Centrum Reumatologii
state: Mazowieckie
city: Bialystok
country: Poland
facility: Gabinet Internistyczno- Reumatologiczny Piotr Adrian Klimiuk
state: Podlaskie
city: Lublin
country: Poland
facility: Zespol Poradni Specjalistycznych REUMED
state: Polska
city: Elblag
country: Poland
facility: Ambulatorium Barbara Bazela
state: Warminsko-Mazurki
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 w Bydgoszczy, Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne S.C.
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Nadarzyn
country: Poland
facility: NZOZ Lecznica MAK-MED s.c.
city: Poznan
country: Poland
facility: Ortopedyczno-Rehabilitacyjny Szpital Kliniczny UM w Poznaniu
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED
city: Napoca
country: Romania
facility: Napoca Emergency Clinical County Hospital
state: Cluj
city: Craiova
country: Romania
facility: Craiova Emergency Clinical County Hospital
state: Dolj
city: Brasov
country: Romania
facility: SC CMDTA Neomed SRL
city: Bucharest
country: Romania
facility: SANA Medical Center
city: Bucharest
country: Romania
facility: St. Maria Clinical Hospital
city: Bucuresti
country: Romania
facility: Spitalul Clinic Sf Maria Bucuresti
city: Bucuresti
country: Romania
facility: Spitalul Clinic "Dr. Ioan Cantacuzino"
city: Bucureti
country: Romania
facility: Spitalul Euroclinic
city: Belgrade
country: Serbia
facility: Institute of Rheumatology
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Niska Banja
country: Serbia
facility: Institute for Treatment and Rehabilitation Niska Banja
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
city: Umhlanga
country: South Africa
facility: Suite 509 Umhlanga Netcare Medical Centre
state: Durban
city: Parktown
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Guateng
city: Muckleneuk
country: South Africa
facility: Jakaranda Hospital
state: Pretoria
city: Cape Town
country: South Africa
facility: Panorama Medical Centre
state: Western Cape
city: Pinelands
country: South Africa
facility: Arthritis Clinical Trial Centre
state: Western Cape
city: Stellenbosch
country: South Africa
facility: Winelands Medical Research Centre
state: Western Cape
city: Pretoria
country: South Africa
facility: University Of Pretoria
city: La Vila Joiosa
country: Spain
facility: Hospital Marina Baixa
state: Alicante
city: Fuenlabrada
country: Spain
facility: Hospital De Fuenlabrada
state: Madrid
city: Vigo
country: Spain
facility: Hospital do Meixoeiro
state: Pontevedra
city: Sabadell
country: Spain
facility: Corporacion Sanitaria Parc Tauli
state: Sapin
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Corporació Sanitària Clínic
city: Sevilla
country: Spain
facility: Hospital Quiron Infanta Luisa
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.