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

• ClinicalTrials.gov Identifier: NCT03616964
• Recruitment Status: Active, not recruiting
• First Posted: August 6, 2018
• Last Update Posted: March 19, 2021
• Sponsor: Eli Lilly and Company
• Collaborator: Incyte Corporation
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Drug: Baricitinib; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 750 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients With Systemic Lupus Erythematosus
• Actual Study Start Date: August 2, 2018
• Estimated Primary Completion Date: October 15, 2021
• Estimated Study Completion Date: November 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Baricitinib High Dose; Baricitinib administered orally. Placebo administered orally to maintain the blind.	Drug: Baricitinib; Administered orally.; Other Name: LY3009104; Drug: Placebo; Administered orally
Experimental: Baricitinib Low Dose; Baricitinib administered orally. Placebo administered orally to maintain the blind.	Drug: Baricitinib; Administered orally.; Other Name: LY3009104; Drug: Placebo; Administered orally
Placebo Comparator: Placebo; Placebo administered orally.	Drug: Placebo; Administered orally

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (High Dose) [ Time Frame: Week 52 ]
   Percentage of participants achieving SRI-4 response (high dose).

Secondary Outcome Measures :

1. Percentage of Participants Achieving SRI-4 Response (Low Dose) [ Time Frame: Week 52 ]
   Percentage of participants achieving SRI-4 response (low dose).
2. Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS) [ Time Frame: Week 52 ]
   Percentage of Participants Achieving a LLDAS.
3. Time to First Severe Flare [ Time Frame: Baseline to Week 52 ]
   Time to first severe flare.
4. Change from Baseline in Prednisone Dose [ Time Frame: Baseline, Week 52 ]
   Change from baseline in prednisone dose.
5. Change from Baseline in Worst Pain Numeric Rating Scale (NRS) [ Time Frame: Baseline, Week 52 ]
   Change from baseline in worst pain NRS.
6. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score [ Time Frame: Baseline, Week 52 ]
   Change from baseline on FACIT-Fatigue total score.
7. 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 [ Time Frame: Week 52 ]
   Percentage of participants with CLASI total activity score ≥10 at baseline with ≥50% reduction in CLASI total activity score.
8. Change from Baseline in Tender Joint Count [ Time Frame: Baseline, Week 52 ]
   Change from baseline in tender joint count.
9. Change from Baseline in Swollen Joint Count [ Time Frame: Baseline, Week 52 ]
   Change from baseline in swollen joint count.
10. Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss) [ Time Frame: Baseline through Week 16 ]
    PK: Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss).
11. Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) [ Time Frame: Baseline through Week 16 ]
    Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss).

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Arizona

University of Arizona Arthritis Center

Gilbert, Arizona, United States, 85297

Arizona Arthritis & Rheumatology Research

Phoenix, Arizona, United States, 85302

Arizona Arthritis & Rheumatology Associates, P. C.

Tucson, Arizona, United States, 85704

United States, California

Wallace Rheumatic Studies Center

Beverly Hills, California, United States, 90211

Medvin Clinical Research - Weidmann

Covina, California, United States, 91722

Office: Dr Robin K Dore

Tustin, California, United States, 92780

Inland Rheumatology & Osteoporosis Medical Group

Upland, California, United States, 91786

United States, Colorado

Denver Arthritis Clinic - Lowry

Denver, Colorado, United States, 80230

United States, Florida

Clinical Research of West Florida

Clearwater, Florida, United States, 33765

Millennium Research

Ormond Beach, Florida, United States, 32174

Integral Rheumatology & Immunology Specialists

Plantation, Florida, United States, 33324

Clinical Research of West Florida

Tampa, Florida, United States, 33603

Tampa Medical Group, P.A.

Tampa, Florida, United States, 33614

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

Northside Hospital

Atlanta, Georgia, United States, 30342

North Georgia Rheumatology, PC

Lawrenceville, Georgia, United States, 30046

United States, Kentucky

Arthritis Center of Lexington

Lexington, Kentucky, United States, 40504

United States, Maryland

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States, 21224-6801

United States, Michigan

Advanced Rheumatology, PC

Lansing, Michigan, United States, 48910

United States, Montana

Glacier View Research Institute - Endocrinology

Kalispell, Montana, United States, 59901

United States, Nevada

Innovative Health Research

Las Vegas, Nevada, United States, 89128

United States, New Mexico

Albuquerque Clinical Trials, Inc.

Albuquerque, New Mexico, United States, 87102

Arthritis and Osteoporosis Associates of New Mexico

Las Cruces, New Mexico, United States, 88011

United States, New York

St. Lawrence Health System

Canton, New York, United States, 13617

New York University Medical Center

New York, New York, United States, 10016

SUNY Upstate Medical University

Syracuse, New York, United States, 13210

United States, North Carolina

Joint and Muscle Medical Care

Charlotte, North Carolina, United States, 28204

Box Arthritis & Rheumatology of the Carolinas, PLLC

Charlotte, North Carolina, United States, 28210

United States, Ohio

Cincinnati Rheumatic Disease Study Group

Cincinnati, Ohio, United States, 45242

United States, Oklahoma

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Clinical Research Center of Reading,LLC

Wyomissing, Pennsylvania, United States, 19610

United States, South Carolina

Articularis Healthcare d/b/a/ Low Country Rheumatology, PA

Summerville, South Carolina, United States, 29486

United States, Tennessee

Eagle Medical

Crossville, Tennessee, United States, 38555

United States, Texas

Dr. Dhiman Basu Private Practice

Colleyville, Texas, United States, 76034

Metroplex Clinical Research Center

Dallas, Texas, United States, 75231

Advanced Rheumatology of Houston

The Woodlands, Texas, United States, 77382

Clear Lake Specialties

Webster, Texas, United States, 77598

United States, Virginia

Arthritis Clinic of Northern VA, P.C.

Arlington, Virginia, United States, 22205

Spectrum Medical Inc.

Danville, Virginia, United States, 24541

Argentina

Aprillus Asistencia e Investigacion - Servicio de neurologia

Caba, Buenos Aires, Argentina, C1046AAQ

DOM Centro de Reumatologia

Ciudad de Buenos Aires, Buenos Aires, Argentina, C1111AAH

Framingham Centro Medico

La Plata, Buenos Aires, Argentina, B1902COS

CER Instituto Medico

Quilmes, Buenos Aires, Argentina, B1878DVC

Instituto de Investigaciones Clinicas Quilmes

Quilmes, Buenos Aires, Argentina, B1878GEG

Comite de Etica en Investigacion - CEMIC

Buenos Aires, Ciudad Autonoma De Buenos Aire, Argentina, C1431FWO

Clinica Adventista Belgrano

Caba, Ciudad Autónoma De Buenos Aire, Argentina, C1430EGF

Sanatorio Británico

Rosario, Santa Fe, Argentina, 2000

Centro Medico Privado de Reumatologia

SAN M. DE Tucuman, Tucumán, Argentina, T4000AXL

Sanatorio Guemes Cardiocirugia

Ciudad Autonoma Buenos Aires, Argentina, C1181AAX

IR Medical Center S.A. Instituto de Reumatologia

Mendoza, Argentina, M5500CPH

Chile

Clinical Research Chile SpA

Valdivia, Los Ríos, Chile, 5110683

Enroll SpA

Providencia, Región Metropolitana De Santia, Chile, 7500587

Clinica Alemana de Osorno

Osorno, Chile, 5290000

Sociedad Medica Del Aparato Locomotor SA

Santiago, Chile, 7510186

Prosalud y cia. Ltda.

Santiago, Chile

ReumaCen Centro Reumatologico Integral

Vina del Mar, Chile, 2570017

Colombia

HPTU-El Hospital con alma Pablo Tobon Uribe

Medellin, Antioquia, Colombia

Clinica de la Costa

Barranquilla, Atlantico, Colombia

Circaribe SAS

Barranquilla, Atlántico, Colombia

Idearg S.A.S.

Bogota, Cundinamarca, Colombia

Centro Integral de Reumatologia e Inmunologia

Bogotá, Cundinamarca, Colombia

Servimed S.A.S.

Bucaramanga, Santander, Colombia, 12345

Centro de Medicina Interna

Cali, Valle Del Cauca, Colombia

Preventive Care Ltdac

Chia, Colombia

France

CHRU Brest - Hopital Cavale Blanche

Brest Cedex, Finistère, France, 29609

Centre hospitalier universitaire de Haut Leveque

Pessac, Gironde, France, 33604

CHU Montpellier Lapeyronie Hospital

Montpellier, Hérault, France, 34295

Centre hospitalier universitaire Pellegrin

Bordeaux, France, 33076

Hopital Européen

Marseille, France, 13003

India

Krishna Institute of Medical Science

Hyderabad, Andhra Pradesh, India, 500003

Panchshil Hospital

Ahmedabad, Gujarat, India, 380005

CIMS Hospital Private Limited

Ahmedabad, Gujarat, India, 380060

NHL Municipal Medical College & VS General Hospital

Ahmedabad, Gujarat, India, 38006

Shree Giriraj Hospital

Rajkot, Gujarat, India, 360004

Nirmal Hospital Private Limited

Surat, Gujarat, India, 395002

Sterling Hospital

Vadodara, Gujarat, India, 390007

St. John Medical College & Hospital

Bangalore, Karnataka, India, 560034

ChanRe Rheumatology And Immunology Center And Research

Bangalore, Karnataka, India, 560079

Sushruta Multispecialty Hospital & Research Center Pvt Ltd

Hubli, Karnataka, India, 580021

Kasturba Medical College Hospital, Mangalore

Madhav Nagar, Manipal, Karnataka, India, 576104

Jasleen Hospital

Nagpur, Maharashtra, India, 44012

Synexus Affiliate - Sujata Birla Hospital & Medical Research Center

Nashik, Maharashtra, India, 422101

Fortis Escorts Hospital

Jaipur, Rajasthan, India, 302017

Italy

Azienda Ospedaliera Universitaria

Modena, MO, Italy, 41124

Azienda Ospedaliera Universitaria Pisana

Pisa, Toscana, Italy, 56100

IRCCS Ospedale Policlinico San Martino

Genova, Italy, 16132

Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico

Milano, Italy, 20122

Azienda Policlinico Umberto I

Roma, Italy, 00161

Azienda Ospedaliera Santa Maria Della Misericordia

Udine, Italy, 33100

Japan

University of Occupational and Enviromental Health

Kitakyushu, Fukuoka, Japan, 807-8556

Hiroshima University Hospital

Hiroshima-shi, Hiroshima-ken, Japan, 734-8551

National Hospital Organization Asahikawa Medical Center

Asahikawa, Hokkaido, Japan, 070-8644

Hokkaido University Hospital

Sapporo, Hokkaido, Japan, 060-8648

Jp Red Cross Society Himeji Hp

Himeji, Hyogo, Japan, 670-8540

Kobe University Hospital

Kobe, Hyogo, Japan, 650-0017

Kagawa University Hospital

Kita-gun, Kagawa, Japan, 761-0793

Tohoku University Hospital

Sendai-shi, Miyagi, Japan, 980-8574

Juntendo University Hospital

Bunkyo-ku, Tokyo, Japan, 113-8431

St. Lukes International Hospital

Chuo-Ku, Tokyo, Japan, 104 8560

Toho University Ohashi Med C

Meguro-ku, Tokyo, Japan, 153-8515

Showa University Hospital

Shinagawa-ku, Tokyo, Japan, 142-8666

Keio University Hospital

Shinjuku-Ku, Tokyo, Japan, 160-8582

National Hospital Organization Kyushu Medical Center

Fukuoka, Japan, 810 8563

Hamanomachi Hospital

Fukuoka, Japan, 810-8539

Nippon Medical School Hospital

Tokyo, Japan, 113-8603

Korea, Republic of

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620

Kyung Pook National University Hospital

Daegu, Korea, Korea, Republic of, 41944

Gachon University Gil Medical Center

Incheon, Korea, Korea, Republic of, 21565

Hanyang University Medical Center

Seoul, Korea, Korea, Republic of, 04763

The Catholic University of Korea-Seoul St. Mary's Hospital

Seocho-Gu, Seoul, Korea, Republic of, 06591

Asan Medical Center

Seoul, Korea, Republic of, 05505

Philippines

Mary Mediatrix Medical Center

Lipa, Batangas, Philippines, 4217

Cebu Doctors Hospital

Cebu City, Cebu, Philippines, 6000

Southern Philippines Medical Center

Davao, Davao Del Norte, Philippines, 8000

Angeles University Foundation and Medical Center

Angeles City, Pampanga, Philippines, 2009

Chong Hua Medical Arts Center

Cebu City, Philippines, 6000

Makati Medical Center

Makati City, Philippines, 1229

St. Luke's Medical Center

Quenzon City, Philippines, 1102

Poland

Niepubliczny Zaklad Opieki Zdrowotnej Biogenes Sp. z o.o.

Wroclaw, Dolnoslaskie, Poland, 53224

Twoja Przychodnia Centrum Medyczne Nowa Sol

Nowa Sol, Lubuskie, Poland, 67-100

Medycyna Kliniczna

Warszawa, Mazowieckie, Poland, 00874

Centrum Medyczne Reuma Park

Warszawa, Mazowieckie, Poland, 02-691

Gabinet Internistyczno- Reumatologiczny Piotr Adrian Klimiuk

Bialystok, Podlaskie, Poland, 15-077

Zespol Poradni Specjalistycznych REUMED

Lublin, Polska, Poland, 20582

Ambulatorium Sp. z o. o.

Elblag, Warminsko-Mazurki, Poland, 82300

Szpital Uniwersytecki Nr 2 w Bydgoszczy, Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej

Bydgoszcz, Poland, 85-168

Centrum Medyczne Pratia Katowice

Katowice, Poland, 40-081

Malopolskie Centrum Medyczne S.C.

Krakow, Poland, 30-510

Centrum Medyczne Plejady

Krakow, Poland, 30363

NZOZ Lecznica MAK-MED s.c.

Nadarzyn, Poland, 05-830

Ortopedyczno-Rehabilitacyjny Szpital Kliniczny UM w Poznaniu

Poznan, Poland, 61-545

Centrum Medyczne AMED

Warszawa, Poland, 03-291

Romania

Napoca Emergency Clinical County Hospital

Napoca, Cluj, Romania, 40006

Craiova Emergency Clinical County Hospital

Craiova, Dolj, Romania, 200642

C.M.D.T.A. Neomed

Brasov, Romania, 500283

SANA Medical Center

Bucharest, Romania, 11025

St. Maria Clinical Hospital

Bucharest, Romania, 11172

Spitalul Clinic Sf Maria Bucuresti

Bucuresti, Romania, 011172

Spitalul Clinic "Dr. Ioan Cantacuzino"

Bucuresti, Romania, 020475

Spitalul Euroclinic

Bucureti, Romania, 014461

Serbia

Clinical Center of Serbia

Belgrade, Serbia, 11000

Institute of Rheumatology

Belgrade, Serbia, 11000

Military Medical Academy

Belgrade, Serbia, 11000

Institute for Treatment and Rehabilitation Niska Banja

Niska Banja, Serbia, 18205

Clinical Center of Vojvodina

Novi Sad, Serbia, 21000

South Africa

Suite 509 Umhlanga Netcare Medical Centre

Umhlanga, Durban, South Africa, 4319

Charlotte Maxeke Johannesburg Academic Hospital

Parktown, Guateng, South Africa, 2000

Jakaranda Hospital

Muckleneuk, Pretoria, South Africa, 0002

Panorama Medical Centre

Cape Town, Western Cape, South Africa, 7506

Arthritis Clinical Trial Centre

Pinelands, Western Cape, South Africa, 7405

Winelands Medical Research Centre

Stellenbosch, Western Cape, South Africa, 7600

University Of Pretoria

Pretoria, South Africa, 0002

Spain

Hospital Marina Baixa

La Vila Joiosa, Alicante, Spain, 03570

Hospital De Fuenlabrada

Fuenlabrada, Madrid, Spain, 28944

Hospital do Meixoeiro

Vigo, Pontevedra, Spain, 36200

Corporacion Sanitaria Parc Tauli

Sabadell, Sapin, Spain, 08208

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Corporació Sanitària Clínic

Barcelona, Spain, 8036

Hospital Quiron Infanta Luisa

Sevilla, Spain, 41010

Sponsors and Collaborators

Eli Lilly and Company

Incyte Corporation

Investigators

• Study Director: 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); Eli Lilly and Company

More Information

Additional Information:

A Study of Baricitinib in Participants With Systemic Lupus Erythematosus 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:CD007478. doi: 10.1002/14651858.CD007478.pub2. Review.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03616964
• Other Study ID Numbers: 16677; I4V-MC-JAIA ( Other Identifier: Eli Lilly and Company ); 2017-005027-25 ( EudraCT Number )
• First Posted: August 6, 2018
• Last Update Posted: March 19, 2021
• Last Verified: March 15, 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eli Lilly and Company:

SLE

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases