An Investigational Study to Evaluate BMS-986165 in Participants With Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title:

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BMS-986165 in Subjects With Systemic Lupus Erythematosus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03252587
• Other study ID #: IM011-021
• Secondary ID: 2017-001203-79
• Status: Completed
• Phase: Phase 2
• Start date: September 21, 2017
• Est. completion date: October 28, 2021

Study information

• Verified date: November 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate BMS-986165 to assess its effects in participants with systemic lupus erythematosus (SLE).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 363
• Est. completion date: October 28, 2021
• Est. primary completion date: June 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Systemic lupus erythematosus (SLE) disease diagnosed = 24 weeks before the screening visit

• Meets the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE

• One of the following: elevated antinuclear antibodies (ANA) = 1:80 or positive anti- double-stranded deoxyribonucleic acid (dsDNA) (positive includes indeterminate results) or positive anti-Smith (anti-Sm) as determined by the central laboratory

• Total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score = 6 points and clinical SLEDAI-2K score = 4 points with joint involvement and/or rash [score must be confirmed by Central Review Services (CRS)]

• Men and women must agree to follow specific methods of contraception, if applicable

Exclusion Criteria:

• Drug-induced SLE, certain other autoimmune diseases, and active, severe lupus nephritis

• SLE overlap syndromes such as scleroderma and mixed connective tissue disease

• Clinically significant abnormalities on chest x-ray or electrocardiogram (ECG)

• History of any significant drug allergy

Other protocol defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• BMS-986165
Specified dose on specified days

Other:
• Placebo
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0166	Caba	Buenos Aires
Argentina	Local Institution - 0136	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Local Institution - 0138	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Local Institution - 0139	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Local Institution - 0185	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Argentina	Local Institution - 0096	Cordoba
Argentina	Local Institution - 0137	Mendoza
Argentina	Local Institution - 0152	Rosario	Santa Fe
Argentina	Local Institution - 0097	San Miguel De Tucum	Tucuman
Australia	Heidelberg Repatriation Hospital	Heidelberg West	Victoria
Australia	Local Institution - 0241	Maroochydore	Queensland
Brazil	Santa Casa de Misericordia de Belo Horizonte	Belo Horizonte	Minas Gerais
Brazil	Local Institution - 0126	Curitiba	Parana
Brazil	Local Institution - 0129	Goiania	Goias
Brazil	Local Institution - 0125	Juiz de Fora	Minas Gerais
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	SAO Paulo
Brazil	Local Institution - 0128	Porto Alegre	RIO Grande DO SUL
Brazil	CITIPA - Centro de Imunoterapia de Ipanema	Rio de Janeiro
Brazil	Local Institution - 0130	Salvador	Bahia
Brazil	Local Institution - 0151	Sao Bernardo do Campo	SAO Paulo
Brazil	Local Institution - 0148	Sao Paulo
Canada	Local Institution - 0247	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	Local Institution - 0245	Toronto	Ontario
Colombia	Local Institution - 0098	Barranquilla
Colombia	Local Institution - 0099	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialidades Medicas (CIREEM)	Bogota
Colombia	Medicity SAS	Bucaramanga
Colombia	Local Institution - 0161	Cali
Colombia	Local Institution - 0100	Chia
Colombia	Local Institution - 0159	Zipaquira
Germany	Allergie-Centrum-Charite Campus Charite Mitte Klinik fur Dermatologie Venerologie und Allergologi	Berlin
Germany	Klinik fur Nieren- und Hochdruckerkrankungen	Hannover
Germany	Universitatsmedizin der Johannes Gutenberg-Universitat Mainz - I. Medizinische Klinik und Poliklin	Mainz
Hungary	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Local Institution - 0035	Gyula
Hungary	Local Institution - 0123	Szeged
Israel	Local Institution	Haifa
Israel	Local Institution	Jerusalem
Israel	Local Institution	Kfar Saba
Israel	Local Institution	Petah Tikva
Israel	Local Institution	Tel-Hashomer
Japan	Local Institution - 0117	Chiba-shi	Chiba
Japan	Local Institution - 0154	Chuo-ku	Tokyo
Japan	Kanazawa University Hospital	Ishikawa
Japan	Local Institution - 0144	Itabashi-ku	Tokyo
Japan	Kameda Clinic	Kamogawa-shi	Chiba
Japan	Local Institution - 0177	Kitakyushu	Fukuoka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Local Institution - 0141	Sapporo-shi	Hokkaido
Japan	Tohoku University Hospital	Sendai City	Miyagi
Japan	Dokkyo Medical University	Shimotsuga-gun	Tochigi
Japan	Local Institution - 0183	Shimotsuke-city	Tochigi
Japan	Keio University Hospital	Shinjuku-Ku	Tokyo
Japan	Local Institution - 0133	Tokyo
Japan	Local Institution - 0162	Tokyo
Japan	National Hospital Organization Tokyo Medical Center	Tokyo
Japan	Showa University Hospital	Tokyo
Japan	Tomishiro Central Hospital	Tomigusuku-shi	Okinawa
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Daejeon
Korea, Republic of	Local Institution - 0253	Gwangju
Korea, Republic of	Local Institution	Incheon
Korea, Republic of	Local Institution - 0054	Seoul
Korea, Republic of	Local Institution - 0050	Suwon
Mexico	Local Institution - 0135	Guadalajara	Jalisco
Mexico	Local Institution - 0172	Leon	Guanajuato
Mexico	Local Institution - 0163	Leon, Guanajuato	Guanajuato
Mexico	Local Institution - 0173	Mexico	Distrito Federal
Mexico	Local Institution - 0140	Mexico City	Distrito Federal
Mexico	Local Institution - 0134	Monterrey	Nuevo LEON
Mexico	Local Institution - 0149	San Luis Potosi
Mexico	Faicic S. de R.L. de C.V.	Veracruz
Mexico	Juan Alberto Rodriguez Ruiz	Zapopan	Jalisco
Mexico	Local Institution - 0156	Zapopan	Jalisco
Poland	Local Institution - 0089	Bydgoszcz
Poland	Niepubliczny Zaklad Opieki Zdrowotnej BIF-MED S.C	Bytom
Poland	Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spolka Partnerska	Elblag
Poland	Centrum Medyczne Pratia w Gdyni	Gdynia
Poland	Silmedic Sp. z o.o.	Katowice
Poland	Zespol Opieki Zdrowotnej w Konskich	Konskie
Poland	Local Institution - 0182	Koscian
Poland	Centrum Medyczne ProMiMed	Krak
Poland	Local Institution - 0211	Krakow
Poland	Local Institution - 0222	Krakow
Poland	REUMED Sp. z o.o.	Lublin
Poland	Medyczne Centrum Hetmanska - Poznan	Poznan
Poland	Niepubliczny Specjalistyczny Zaklad Opieki Zdrowotnej Med-Polonia	Poznan
Poland	Solumed Centrum Medyczne	Poznan
Poland	Local Institution - 0093	Sosnowiec
Poland	SANUS Szpital Specjalistyczny	Stalowa Wola
Poland	Centrum Medyczne AMED Warszawa Targowek	Warszawa
Poland	Local Institution - 0090	Warszawa
Poland	Local Institution - 0192	Warszawa
Poland	Local Institution - 0219	Warszawa
Poland	Local Institution - 0025	Wroclaw
Poland	Local Institution - 0077	Wroclaw
Poland	Local Institution - 0184	Wroclaw
Romania	Neomed Research	Brasov
Romania	Centrul Medical Sana	Bucuresti
Romania	Spitalul Clinic Dr. Ioan Cantacuzino	Bucuresti
Romania	Spitalul Sfanta Maria	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Cluj-Napoca	Cluj-Napoca
Romania	Spitalul Clinic Jude?an de Urgen? Sfantul Apostol Andrei	Galati
Romania	Spitalul Judetean de Urgenta Valcea	Ramnicu Valcea
Russian Federation	CjSC	Ekaterinburg
Russian Federation	Kemerovo State Medical University	Kemerovo
Russian Federation	Medical Center Maksimum Zdorovia	Kemerovo
Russian Federation	Local Institution - 0210	Novosibirsk
Russian Federation	Local Institution - 0006	Orenburg
Russian Federation	State Healthcare Institution of the Republic of Karelia-Republican Hospital im.V.A.Baranova	Petrozavodsk
Russian Federation	Local Institution - 0207	Saint - Petersburg
Russian Federation	Clinical Rheumatological Hospital Number 25	Saint Petersburg
Russian Federation	Polyclinic of Private Security Personnel	Saint Petersburg
Russian Federation	Private Healthcare Institution Clinical Hospital	Smolensk
Russian Federation	Local Institution - 0223	St. Petersburg
Russian Federation	Tolyatti city clinical hospital ?	Tolyatti
Russian Federation	Biomed	Vladimir
Russian Federation	Local Institution - 0208	Yaroslavl
Russian Federation	State Budgetary Healthcare Institution of the Yaroslavl Region Clinical Hospital No. 2	Yaroslavl
Spain	Complejo Hospitalario Universitario A Coruna	A Coru
Spain	Hospital Universitari Vall dHebron	Barcelona
Spain	Hospital Regional Universitario de Malaga Hospital General	Malaga
Spain	Hospital de Merida	Merida
Spain	Corporacio Sanitaria Parc Tauli	Sabadell
Spain	Local Institution - 0228	Sevilla
Taiwan	Local Institution	Changhua City
Taiwan	Local Institution - 0114	Taichung
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taipei
Taiwan	Local Institution - 0088	Taipei
Taiwan	Local Institution	Taipei City
Taiwan	Local Institution	Taoyuan
United States	Local Institution - 0206	Atlanta	Georgia
United States	Local Institution - 0086	Austin	Texas
United States	Local Institution - 0087	Austin	Texas
United States	Local Institution - 0010	Aventura	Florida
United States	Local Institution - 0178	Birmingham	Alabama
United States	Local Institution - 0066	Brandon	Florida
United States	Local Institution - 0011	Brooklyn	New York
United States	SUNY Downstate Health Science University	Brooklyn	New York
United States	Local Institution - 0119	Chapel Hill	North Carolina
United States	Local Institution - 0190	Charleston	South Carolina
United States	Local Institution - 0026	Charlotte	North Carolina
United States	Local Institution - 0171	Chesapeake	Virginia
United States	Klein & Associates	Cumberland	Maryland
United States	Pioneer Research Solutions	Cypress	Texas
United States	Baylor Research Institute	Dallas	Texas
United States	Local Institution - 0193	Dallas	Texas
United States	Local Institution - 0022	Decatur	Georgia
United States	Local Institution - 0023	El Cajon	California
United States	Local Institution - 0034	Farmington	Connecticut
United States	Local Institution - 0214	Gainesville	Florida
United States	Klein and Associates	Hagerstown	Maryland
United States	Local Institution - 0061	Houston	Texas
United States	Local Institution - 0204	Houston	Texas
United States	Local Institution - 0001	Jackson	Tennessee
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	BioSolutions Clinical Research Center	La Mesa	California
United States	Local Institution - 0082	Lake Success	New York
United States	Advanced Rheumatology - Lansing	Lansing	Michigan
United States	Local Institution - 0083	Lawrenceville	Georgia
United States	Little Rock Diagnostic Clinic	Little Rock	Arkansas
United States	Los Angeles County Hospital and University of Southern California Medical Center	Los Angeles	California
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Local Institution - 0047	Mesquite	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	Local Institution - 0195	New Haven	Connecticut
United States	Local Institution - 0109	New York	New York
United States	Local Institution - 0232	New York	New York
United States	Local Institution - 0180	Oklahoma City	Oklahoma
United States	Local Institution - 0197	Oklahoma City	Oklahoma
United States	University of California at Irvine College of Medicine	Orange	California
United States	Local Institution - 0233	Orlando	Florida
United States	Local Institution - 0057	Ormond Beach	Florida
United States	Local Institution - 0227	Palm Desert	California
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Arthritis and Osteoporosis Center of South Texas	San Antonio	Texas
United States	University of Washington	Seattle	Washington
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Arthritis Research and Treatment Center	Stockbridge	Georgia
United States	Local Institution - 0002	Tamarac	Florida
United States	BayCare Medical Group	Tampa	Florida
United States	Local Institution - 0038	Tampa	Florida
United States	Millennium Clinical Trials - Thousand Oaks	Thousand Oaks	California
United States	The Lundquist Institute at Harbor-UCLA Medical Center	Torrance	California
United States	Inland Rheumatology Clinical Trials	Upland	California
United States	Local Institution - 0174	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Colombia,  Germany,  Hungary,  Israel,  Japan,  Korea, Republic of,  Mexico,  Poland,  Romania,  Russian Federation,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Meet Response Criteria for Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] at Week 32	SRI(4) responder is defined as a patient whose disease course fulfills all of the following: A 4-point or greater reduction from baseline in SLEDAI-2K score; No new British Isles Lupus Assessment Group (BILAG) A (severe disease activity) and not more than 1 new BILAG B (moderate disease activity) organ domain grade; No worsening from baseline in the Physician's Global Assessment of Disease Activity Scale by more than 0.3 points on a 3-point visual analog scale from no disease activity to severe disease activity	At week 32
Secondary	Number of Participants Who Meet Response Criteria for Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] at Week 48	SRI(4) responder is defined as a patient whose disease course fulfills all of the following: A 4-point or greater reduction from baseline in SLEDAI-2K score; No new British Isles Lupus Assessment Group (BILAG) A (severe disease activity) or not more than 1 new BILAG B (moderate disease activity) organ domain grade; No worsening from baseline in the Physician's Global Assessment of Disease Activity Scale by more than 0.3 points on a 3-point visual analog scale from no disease activity to severe disease activity	At week 48
Secondary	Number of Participants Who Achieve British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) Response	BICLA responder is defined as a patient whose disease course fulfills all of the following: Improvement in all organ systems with activity graded as BILAG-2004 A (severe disease activity) or B (moderate disease activity) at baseline; No new organ system with activity graded as BILAG A; no more than 1 new organ system with activity graded as BILAG B; No increase from baseline in Systemic Lupus Erythematosus SLEDAI-2K score (= 0 points for change from baseline score); No increase = 10% in the Physician's Global Assessment of Disease Activity on a 3-point visual analog scale from no disease activity to severe disease activity; No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessment	At week 48
Secondary	Number of Participants Who Achieve Lupus Low Disease Activity State (LLDAS)	LLDAS is defined as follows: SLEDAI-2K = 4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity measured as maintaining a D (no disease activity but suggests the system had previously been affected) or E (no current or previous disease activity) score in BILAG Gastrointestinal Body System; No new lupus disease activity compared with the previous assessment measured as no new or worsening individual BILAG parameters; Physician's Global Assessment of Disease Activity = 1 on a 3-point visual analog scale from no disease activity to severe disease activity; A current prednisolone (or equivalent) dose = 7.5 mg daily; Well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents	At Week 48
Secondary	Number of Participants With a =50% Reduction in CLASI Activity Score in the Sub-group With Baseline CLASI Activity Score =10	Number of participants with a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score = 10 at baseline who achieve a CLASI response, defined as a decrease of = 50% from baseline CLASI activity score (ranges from 0-70, where a higher score is associated with high disease activity). CLASI assesses by body surface area; points are given for presence of erythema, scale, hypertrophy, mucous membrane lesions, recent hair loss, and physician-observed alopecia	At week 48
Secondary	Change From Baseline in the 40-Joint Count	Change from baseline in the following 40-joint count: phalangeal joints of the hand, second through fifth metacarpophalangeal joints of the hand, and individual metatarsophalangeal joints of the feet, Bilateral first metacarpophalangeal joints and shoulders. Each of 40 joints count is evaluated based upon the presence or absence of: Tender joint count (0 to 40); Swollen joint count (0 to 40); Tender and swollen joint count (0 to 40) A larger joint count indicates more severe disease.	Baseline and week 48
Secondary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with any grade adverse events (AEs) and any grade serious adverse events (SAEs). An adverse event (AE) including SAEs is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in participants that do not necessarily have causal relationship with treatment	From first dose to 30 days post last dose (Up to 52 weeks)
Secondary	Number of Participants With Laboratory Abnormalities in Specific Liver Tests	Number of participants with laboratory abnormalities in specific liver tests based on US conventional units. The potential drug-induced liver injury is defined by the presence of all of the following: Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) elevation > 3× Upper Limit of Normal (ULN); Total bilirubin > 2× ULN, without initial findings of cholestasis (elevated serum alkaline phosphatase); No other immediately apparent possible causes of AST or AST elevation and hyperbilirubinemia, including, but not limited to, viral hepatitis, preexisting chronic or acute liver disease, or the administration of other drug(s) known to be hepatotoxic	From first dose to 30 days post last dose (Up to 52 weeks)
Secondary	Number of Participants With Abnormalities in Vital Signs	Number of participants with abnormalities in vital signs including heart rate, systolic blood pressure, and diastolic blood pressure	From first dose to 30 days post last dose (Up to 52 weeks)
Secondary	Number of Participants With Abnormalities in Electrocardiograms (ECGs)	Number of participants with abnormalities in electrocardiograms (ECGs) assessed by QTcF, PR interval, and QRS interval	From baseline to up to week 48
Secondary	BMS-986165 and Its Active Metabolite BMT-153261 Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration (Cmax) for the following treatments: BMS-986165 and its active metabolite BMT-153261. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.	Pre-dose, 0.5, 2, 4, and 6 hours post dose on week 12
Secondary	BMS-986165 and Its Active Metabolite BMT-153261 Time of Maximum Observed Plasma Concentration (Tmax)	Time of maximum observed plasma concentration (Tmax) for the following treatments: BMS-986165 and its active metabolite BMT-153261.	Pre-dose, 0.5, 2, 4, 6, and 10 hours post dose on week 12
Secondary	BMS-986165 and Its Active Metabolite BMT-153261 Trough Observed Plasma Concentration (Ctrough)	Trough observed plasma concentration (Ctrough) for the following treatments: BMS-986165 and its active metabolite BMT-153261. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.	Pre-dose, 0.5, 2, 4, and 6 hours post dose on week 2, 4, 8, 12, 24, 32, and 48
Secondary	Percent Change From Baseline in Interferon-Regulated Gene (IRG) Expression Levels	Percent change from baseline in interferon-regulated gene (IRG) expression levels. IRG-high vs. IRG-low was determined using a 5-interferon (IFN) gene set during the sample collected at screening period. Baseline values are defined as the last measurement before the first dose.	From baseline to week 44
Secondary	Percent Change From Baseline in Interferon-Regulated Gene (IRG) Expression Levels at Week 32	Percent change from baseline in interferon-regulated gene (IRG) expression levels. IRG-high vs. IRG-low was determined using a 5-interferon (IFN) gene set during the sample collected at screening period. Baseline values are defined as the last measurement before the first dose.	From baseline to week 32
Secondary	Percent Change From Baseline in Complement Proteins C3 and C4 Levels	Percent change from baseline in complement proteins C3 and C4 levels. Baseline values are defined as the last measurement before the first dose.	From baseline to week 52
Secondary	Percent Change From Baseline in Complement (C3, C4) Levels at Week 32	Percent change from baseline in complement proteins C3 and C4 levels. Baseline values are defined as the last measurement before the first dose.	From baseline to week 32
Secondary	Percent Change From Baseline in Anti-Double-Stranded DNA (dsDNA) Antibody Levels	Percent change from baseline in anti-double-stranded DNA (dsDNA) levels. Baseline values are defined as the last measurement before the first dose.	From baseline to week 52
Secondary	Percent Change From Baseline in Anti-Double-Stranded DNA (dsDNA) Antibody Levels at Week 32	Percent change from baseline in anti-double-stranded DNA (dsDNA) levels. Baseline values are defined as the last measurement before the first dose.	From baseline to week 32
Secondary	Number of Participants With Global Systemic Lupus Erythematosus (SLE) Clinical Response Based on Interferon-Regulated Gene (IRG) Status	Global systemic lupus erythematosus (SLE) clinical response in participants based on interferon-regulated gene (IRG) status (high versus low IRG signature). IRG-high vs. IRG-low was determined using a 5-interferon (IFN) gene set during the sample collected at screening period. SRI(4) responder is defined as a patient whose disease course fulfills all of the following: A 4-point or greater reduction from baseline in SLEDAI-2K score; No new British Isles Lupus Assessment Group (BILAG) A (severe disease activity) or not more than 1 new BILAG B (moderate disease activity) organ domain grade; No worsening from baseline in the Physician's Global Assessment of Disease Activity Scale by more than 0.3 points on a 3-point visual analog scale from no disease activity to severe disease activity	At week 32

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