A Study of Baricitinib in Participants With Systemic Lupus Erythematosus (SLE-BRAVE II)

Systemic Lupus Erythematosus Clinical Trial

— BRAVE II  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients With Systemic Lupus Erythematosus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03616964
• Other study ID #: 16677
• Secondary ID: I4V-MC-JAIA2017-
• Status: Completed
• Phase: Phase 3
• Start date: August 2, 2018
• Est. completion date: October 20, 2021

Study information

• Verified date: November 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 778
• Est. completion date: October 20, 2021
• Est. primary completion date: September 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Baricitinib
Administered orally.
• Placebo
Administered orally

Locations

Country	Name	City	State
Argentina	Comite de Etica en Investigacion - CEMIC	Buenos Aires	Ciudad Autonoma De Buenos Aire
Argentina	Aprillus Asistencia e Investigacion - Servicio de neurologia	Caba	Buenos Aires
Argentina	Clinica Adventista Belgrano	Caba	Ciudad Autónoma De Buenos Aire
Argentina	Sanatorio Guemes Cardiocirugia	Ciudad Autonoma Buenos Aires
Argentina	DOM Centro de Reumatologia	Ciudad de Buenos Aires	Buenos Aires
Argentina	Framingham Centro Medico	La Plata	Buenos Aires
Argentina	IR Medical Center S.A. Instituto de Reumatologia	Mendoza
Argentina	CER Instituto Medico	Quilmes	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Quilmes	Quilmes	Buenos Aires
Argentina	Sanatorio Británico	Rosario	Santa Fe
Argentina	Centro Medico Privado de Reumatologia	SAN M. DE Tucuman	Tucumán
Chile	Clinica Alemana de Osorno	Osorno
Chile	Enroll SpA	Providencia	Región Metropolitana De Santia
Chile	Prosalud y cia. Ltda.	Santiago
Chile	Sociedad Medica Del Aparato Locomotor SA	Santiago
Chile	Clinical Research Chile SpA	Valdivia	Los Ríos
Chile	ReumaCen Centro Reumatologico Integral	Vina del Mar
Colombia	Circaribe SAS	Barranquilla	Atlántico
Colombia	Clinica de la Costa	Barranquilla	Atlantico
Colombia	Idearg S.A.S.	Bogota	Cundinamarca
Colombia	Centro Integral de Reumatologia e Inmunologia	Bogotá	Cundinamarca
Colombia	Servimed S.A.S.	Bucaramanga	Santander
Colombia	Centro de Medicina Interna	Cali	Valle Del Cauca
Colombia	Preventive Care Ltdac	Chia
Colombia	HPTU-El Hospital con alma Pablo Tobon Uribe	Medellin	Antioquia
France	Centre hospitalier universitaire Pellegrin	Bordeaux
France	CHRU Brest - Hopital Cavale Blanche	Brest Cedex	Finistère
France	Hopital Européen	Marseille
France	CHU Montpellier Lapeyronie Hospital	Montpellier	Hérault
France	Centre hospitalier universitaire de Haut Leveque	Pessac	Gironde
India	CIMS Hospital Private Limited	Ahmedabad	Gujarat
India	NHL Municipal Medical College & VS General Hospital	Ahmedabad	Gujarat
India	Panchshil Hospital	Ahmedabad	Gujarat
India	ChanRe Rheumatology And Immunology Center And Research	Bangalore	Karnataka
India	St. John Medical College & Hospital	Bangalore	Karnataka
India	Sushruta Multispecialty Hospital & Research Center Pvt Ltd	Hubli	Karnataka
India	Krishna Institute of Medical Science	Hyderabad	Andhra Pradesh
India	Fortis Escorts Hospital	Jaipur	Rajasthan
India	Kasturba Medical College Hospital, Mangalore	Madhav Nagar, Manipal	Karnataka
India	Jasleen Hospital	Nagpur	Maharashtra
India	Synexus Affiliate - Sujata Birla Hospital & Medical Research Center	Nashik	Maharashtra
India	Shree Giriraj Hospital	Rajkot	Gujarat
India	Nirmal Hospital Private Limited	Surat	Gujarat
India	Sterling Hospital	Vadodara	Gujarat
Italy	IRCCS Ospedale Policlinico San Martino	Genova
Italy	Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria	Modena	MO
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa	Toscana
Italy	Azienda Policlinico Umberto I	Roma
Italy	Azienda Ospedaliera Santa Maria Della Misericordia	Udine
Japan	National Hospital Organization Asahikawa Medical Center	Asahikawa	Hokkaido
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
Japan	St. Lukes International Hospital	Chuo-Ku	Tokyo
Japan	Hamanomachi Hospital	Fukuoka
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	Jp Red Cross Society Himeji Hp	Himeji	Hyogo
Japan	Hiroshima University Hospital	Hiroshima-shi	Hiroshima-ken
Japan	Kagawa University Hospital	Kita-gun	Kagawa
Japan	University of Occupational and Enviromental Health	Kitakyushu	Fukuoka
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	Toho University Ohashi Med C	Meguro-ku	Tokyo
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Tohoku University Hospital	Sendai-shi	Miyagi
Japan	Showa University Hospital	Shinagawa-ku	Tokyo
Japan	Keio University Hospital	Shinjuku-Ku	Tokyo
Japan	Nippon Medical School Hospital	Tokyo
Korea, Republic of	Kyung Pook National University Hospital	Daegu	Korea
Korea, Republic of	Gachon University Gil Hospital	Incheon	Korea
Korea, Republic of	The Catholic University of Korea-Seoul St. Mary's Hospital	Seocho-Gu	Seoul
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Hanyang University Medical Center	Seoul	Korea
Philippines	Angeles University Foundation and Medical Center	Angeles City	Pampanga
Philippines	Cebu Doctors Hospital	Cebu City	Cebu
Philippines	Chong Hua Medical Arts Center	Cebu City
Philippines	Southern Philippines Medical Center	Davao	Davao Del Norte
Philippines	Mary Mediatrix Medical Center	Lipa	Batangas
Philippines	Makati Medical Center	Makati City
Philippines	St. Luke's Medical Center	Quenzon City
Poland	Gabinet Internistyczno- Reumatologiczny Piotr Adrian Klimiuk	Bialystok	Podlaskie
Poland	Szpital Uniwersytecki Nr 2 w Bydgoszczy, Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej	Bydgoszcz
Poland	Ambulatorium Barbara Bazela	Elblag	Warminsko-Mazurki
Poland	Centrum Medyczne Pratia Katowice	Katowice
Poland	Centrum Medyczne Plejady	Krakow
Poland	Malopolskie Centrum Medyczne S.C.	Krakow
Poland	Zespol Poradni Specjalistycznych REUMED	Lublin	Polska
Poland	NZOZ Lecznica MAK-MED s.c.	Nadarzyn
Poland	Twoja Przychodnia Centrum Medyczne Nowa Sol	Nowa Sol	Lubuskie
Poland	Ortopedyczno-Rehabilitacyjny Szpital Kliniczny UM w Poznaniu	Poznan
Poland	Centrum Medyczne AMED	Warszawa
Poland	Medycyna Kliniczna	Warszawa	Mazowieckie
Poland	Reumatika - Centrum Reumatologii	Warszawa	Mazowieckie
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Biogenes Sp. z o.o.	Wroclaw	Dolnoslaskie
Romania	SC CMDTA Neomed SRL	Brasov
Romania	SANA Medical Center	Bucharest
Romania	St. Maria Clinical Hospital	Bucharest
Romania	Spitalul Clinic "Dr. Ioan Cantacuzino"	Bucuresti
Romania	Spitalul Clinic Sf Maria Bucuresti	Bucuresti
Romania	Spitalul Euroclinic	Bucureti
Romania	Craiova Emergency Clinical County Hospital	Craiova	Dolj
Romania	Napoca Emergency Clinical County Hospital	Napoca	Cluj
Serbia	Institute of Rheumatology	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	University Clinical Center of Serbia	Belgrade
Serbia	Institute for Treatment and Rehabilitation Niska Banja	Niska Banja
Serbia	Clinical Center of Vojvodina	Novi Sad
South Africa	Panorama Medical Centre	Cape Town	Western Cape
South Africa	Jakaranda Hospital	Muckleneuk	Pretoria
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Parktown	Guateng
South Africa	Arthritis Clinical Trial Centre	Pinelands	Western Cape
South Africa	University Of Pretoria	Pretoria
South Africa	Winelands Medical Research Centre	Stellenbosch	Western Cape
South Africa	Suite 509 Umhlanga Netcare Medical Centre	Umhlanga	Durban
Spain	Corporació Sanitària Clínic	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital De Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Marina Baixa	La Vila Joiosa	Alicante
Spain	Corporacion Sanitaria Parc Tauli	Sabadell	Sapin
Spain	Hospital Quiron Infanta Luisa	Sevilla
Spain	Hospital do Meixoeiro	Vigo	Pontevedra
United States	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico
United States	Arthritis Clinic of Northern VA, P.C.	Arlington	Virginia
United States	Emory University	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Wallace Rheumatic Studies Center	Beverly Hills	California
United States	St. Lawrence Health System	Canton	New York
United States	Box Arthritis & Rheumatology of the Carolinas, PLLC	Charlotte	North Carolina
United States	Joint and Muscle Medical Care	Charlotte	North Carolina
United States	Cincinnati Rheumatic Disease Study Group	Cincinnati	Ohio
United States	Clinical Research of West Florida, Inc. (Clearwater)	Clearwater	Florida
United States	Dr. Dhiman Basu Private Practice	Colleyville	Texas
United States	Medvin Clinical Research - Weidmann	Covina	California
United States	Eagle Medical	Crossville	Tennessee
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	Spectrum Medical Inc.	Danville	Virginia
United States	Denver Arthritis Clinic - Lowry	Denver	Colorado
United States	University of Arizona Arthritis Center	Gilbert	Arizona
United States	Glacier View Research Institute - Endocrinology	Kalispell	Montana
United States	Advanced Rheumatology, PC	Lansing	Michigan
United States	Arthritis and Osteoporosis Associates of New Mexico	Las Cruces	New Mexico
United States	Innovative Health Research	Las Vegas	Nevada
United States	North Georgia Rheumatology, PC	Lawrenceville	Georgia
United States	Arthritis Center of Lexington	Lexington	Kentucky
United States	New York University Medical Center	New York	New York
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Millennium Research	Ormond Beach	Florida
United States	Arizona Arthritis & Rheumatology Research	Phoenix	Arizona
United States	Integral Rheumatology & Immunology Specialists	Plantation	Florida
United States	Articularis Healthcare d/b/a/ Low Country Rheumatology, PA	Summerville	South Carolina
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Clinical Research of West Florida	Tampa	Florida
United States	Tampa Medical Group, P.A.	Tampa	Florida
United States	Advanced Rheumatology of Houston	The Woodlands	Texas
United States	Arizona Arthritis & Rheumatology Associates, P. C.	Tucson	Arizona
United States	Office: Dr Robin K Dore	Tustin	California
United States	Inland Rheumatology & Osteoporosis Medical Group	Upland	California
United States	Clear Lake Specialties	Webster	Texas
United States	Clinical Research Center of Reading,LLC	Wyomissing	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Incyte Corporation

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Colombia,  France,  India,  Italy,  Japan,  Korea, Republic of,  Philippines,  Poland,  Romania,  Serbia,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (4 mg Baricitinib)	SRI-4 response defined as 1)greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score 2)no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and 3)no worsening in Physician Global Assessment (PGA) of Disease Activity (worsening defined as an increase of >=0.3 from baseline on a 0-3 visual analogue scale).; SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms,or laboratory parameters related to Systemic Lupus Erythematosus (SLE),divided into 9 organ systems. For each organ system A=severe disease,B=moderate disease,C=mild stable disease,D=inactive,but previously active,E=inactive and never affected. PGA assess disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe).	Week 52
Secondary	Percentage of Participants Achieving SRI-4 Response (2 mg Baricitinib)	SRI-4 response defined as 1)greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score 2)no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and 3)no worsening in Physician Global Assessment (PGA) of Disease Activity (worsening defined as an increase of >=0.3 from baseline on a 0-3 visual analogue scale).; SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms,or laboratory parameters related to Systemic Lupus Erythematosus (SLE),divided into 9 organ systems. For each organ system A=severe disease,B=moderate disease,C=mild stable disease,D=inactive,but previously active,E=inactive and never affected. PGA assess disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe).	Week 52
Secondary	Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS)	The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (CNS, vascular, renal, cardiorespiratory and constitutional); where "no activity" is defined as all items of SLEDAI-2K within these major organ systems equal to 0. (2) no new features of lupus disease activity compared to previous occurred visit, where the "new feature" is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; (3) PGA (scale 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg daily.	Week 52
Secondary	Time to First Severe Flare	Time to first severe flare analyzed using a Cox proportional hazards model with treatment group, baseline disease activity [Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) <10; SLEDAI-2K =10], baseline corticosteroid dose (<10 mg/day; =10 mg/day prednisone or equivalent), and region fitted as explanatory variables. Participants who did not have severe flare during the flare exposure time period were censored at the end of the flare exposure time.	Baseline to Week 52
Secondary	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	For the analysis of steroid use, steroid dosages were converted to a prednisone equivalent in mg. A responder was defined as having a prednisone reduction by >=25% from Baseline to <=7.5 mg/day during Weeks 40 through 52.	Baseline, Week 40 through Week 52
Secondary	Change From Baseline in Worst Pain Numeric Rating Scale (NRS)	Participants assessed the worst pain in the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The average worst daily pain score was calculated as the mean of the scores over the last 7 days prior to each assessment time point. Higher score indicated severe pain. Least Squares (LS) mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >= 10 mg/day prednisone or equivalent), region (North America, Central/South, America/Mexico, Europe, Asia Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.	Baseline, Week 52
Secondary	Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score	FACIT-Fatigue score calculated according to a 13-item questionnaire that assess self reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status. Least Squares (LS) mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >= 10 mg/day prednisone or equivalent), region (North America, Central/South, America/Mexico, Europe, Asia Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.	Baseline, Week 52
Secondary	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	The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations.	Week 52
Secondary	Change From Baseline in Tender Joint Count	The number of tender and painful joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as tender or not tender. LS mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.	Baseline, Week 52
Secondary	Change From Baseline in Swollen Joint Count	The number of swollen joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as swollen or not swollen. LS mean was calculated using MMRM analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.	Baseline, Week 52
Secondary	Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve for Dosing Interval of Baricitinib at Steady State (AUCtau,ss)	AUCtau,ss reported for participants who received multiple doses of mg baricitinib was derived by a population pharmacokinetics approach.	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
Secondary	Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss)	PK: Maximum Concentration of Baricitinib at steady-state (Cmax,ss) was derived by a population pharmacokinetics approach.	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

External Links

•   A Study of Baricitinib in Participants With Systemic Lupus Erythematosus