A Study of Ustekinumab in Participants With Active Systemic Lupus Erythematosus

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03517722
• Collaborator: (none)
• Enrollment: 516
• Locations: 204
• Arms: 2
• Actual Duration (Months): 30.7
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of ustekinumab in participants with active systemic lupus erythematosus (SLE) who have not adequately responded to one or more standard of care treatments.

Condition or Disease	Intervention/Treatment	Phase
Lupus Erythematosus, Systemic	Drug: Placebo; Drug: Ustekinumab (approximately 6 mg/kg); Drug: Ustekinumab 90 mg	Phase 3

Detailed Description

This study evaluates the efficacy, safety, and tolerability of ustekinumab in participants with active SLE according to Systemic Lupus International Collaborating Clinics (SLICC) criteria Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score greater than (>=) 6, despite receiving one or more standard-of-care treatments (example, immunomodulators, antimalarial drugs, and/or glucocorticoids). The total duration of the study is up to 182 weeks, consisting of 3 study periods: a screening period (approximately 6 weeks), a double blind period (52 weeks), and an extension period (124 weeks). Other study evaluations will include pharmacokinetics, immunogenicity, biomarkers and pharmacogenomic evaluations. The safety of the participants enrolled in the study will be monitored on an ongoing basis throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 516 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Subjects With Active Systemic Lupus Erythematosus
• Actual Study Start Date: Apr 16, 2018
• Actual Primary Completion Date: Nov 5, 2020
• Actual Study Completion Date: Nov 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ustekinumab Participants will receive ustekinumab approximately 6 milligram per kilogram (mg/kg) intravenously (IV) based on body weight-range at Week 0 followed by 90 mg ustekinumab subcutaneously (SC) at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. Eligible participants who will enter the extension period will continue to receive 90 mg ustekinumab SC q8w through Week 160.	Drug: Ustekinumab (approximately 6 mg/kg); Participants will receive ustekinumab approximately 6 mg/kg via IV route based on body weight-range.; Other Names: Stelara ; Drug: Ustekinumab 90 mg; Participants will receive 90 mg ustekinumab via SC route.; Other Names: Stelara
Experimental: Placebo Participants will receive matching placebo to ustekinumab IV at Week 0, followed by matching placebo to ustekinumab SC at Week 8 and q8w thereafter through Week 48 during double-blind period. Eligible participants who will enter the extension period will cross-over to receive 90 mg ustekinumab SC q8w through Week 160.	Drug: Placebo; Participants will receive placebo matching to ustekinumab IV or SC.; Drug: Ustekinumab 90 mg; Participants will receive 90 mg ustekinumab via SC route.; Other Names: Stelara

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Composite Response at Week 52 [Week 52]

   SRI-4 response:>=4-point reduction in SLEDAI-2K total score, no British Isles Lupus Assessment Group (BILAG) A (severe disease) and no more than 1 new BILAG B (moderate disease) domain score and no worsening (<10 % increase)from baseline in Physician's Global Assessment(PGA).SLEDAI measures disease activity in 9 organ systems,higher scores=more severe disease activity.Each organ system measured as either absent/present within last 30 days and weighted score across systems was utilized to calculate total SLEDAI score(range:0=no symptoms to 105=presence of all defined symptoms). Improvement is defined as reduction in SLEDAI score (BILAG) Index: assessing clinical signs, symptoms,or laboratory parameters related to SLE,divided into 9 domains. Each domain can range from A=new domain activity, B=worse domain activity, C=same domain activity, D=improving domain activity to E=absence of domain activity. PGA assesses disease activity on visual analogue scale from very well(0)-very poor(10).

Secondary Outcome Measures

1. Time to First Flare [Up to Week 52]

   Time to flare is defined as the time (in days) post baseline when the first flare occurs. It was calculated with flare defined as either 1 or more BILAG A (severe disease activity) or 2 or more new BILAG B (moderate disease activity) domain scores relative to baseline. BILAG was defined as a measure of alterations or intensification to therapy consisting of 97 questions in 9 domains. Each domain can range from A=new domain activity, B=worse domain activity, C=same domain activity, D=improving domain activity to E=absence of domain activity. BILAG A flare was defined as at least 1 new BILAG A scores. BILAG B flare was defined as at least 2 new BILAG B scores.

2. Percentage of Participants With an SRI-4 Composite Response at Week 24 [Week 24]

   SRI-4 response:>=4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no BILAG A (severe disease) and no more than 1 new BILAG B (moderate disease) domain score and no worsening (<10 % increase)from baseline in PGA.SLEDAI measures disease activity in 9 organ systems, higher scores=more severe disease activity. Each organ system measured as either absent/present within last 30 days and weighted score across systems was utilized to calculate total SLEDAI score(range:0=no symptoms to 105=presence of all defined symptoms). Improvement is defined as reduction in SLEDAI score (BILAG) Index: assessing clinical signs, symptoms,or laboratory parameters related to SLE,divided into 9 domains. Each domain can range from A=new domain activity, B=worse domain activity, C=same domain activity, D=improving domain activity to E=absence of domain activity. PGA assesses disease activity on visual analogue scale from very well(0)-very poor(10).

3. Percentage of Participants With 50 Percent (%) Improvement in Joints With Pain and Signs of Inflammation (Active Joints) at Week 52 [Week 52]

   The percentage of participants who achieved at least 50% improvement from baseline in number of joints with pain and signs of inflammation at Week 52 for participants with at least 4 joints with pain and signs of inflammation at baseline were reported.

4. Percentage of Participants Receiving Glucocorticoid at Baseline Who Achieved Change in Glucocorticoid Dose by Week 40 and Sustain That Change Through Week 52 [Up to Week 52]

   Reduction of glucocorticoid dose was defined as a reduction in average daily oral glucocorticoid dose by at least 50% (relative to the baseline dose) or reduction of average daily oral glucocorticoid dose by at least 25% (relative to the baseline dose) so that the average daily dose was reduced to less than or equal to (<=) 7.5 milligram (mg) (prednisone or equivalent). Sustained reduction of glucocorticoid dose was defined as achieving an average daily oral glucocorticoid dose reduction between Weeks 24 and 40, and sustaining that reduction through Week 52, in those participants who, at baseline, were receiving oral glucocorticoids.

5. Percentage of Participants With at Least a 50% Improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 52 [Week 52]

   Percentage of participants achieving at least 50% improvement in CLASI activity score at Week 52 reported in participants with a CLASI activity score of 4 or greater at baseline. The CLASI is an instrument to assess the disease activity and damage caused to the skin for cutaneous lupus erythematosus participants with or without systemic involvement. The CLASI activity score ranges from 0-70 with lower score being improved. Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss, and non-scarring alopecia.

6. Percentage of Participants Receiving Glucocorticoid at Baseline Who Achieved Change in Glucocorticoid Dose by Week 40, Sustained That Change Through Week 52, and Achieved an SRI-4 Composite Response at Week 52 [Up to Week 52]

   Percentage of participants with reduction in glucocorticoid dose by Week 40, its sustenance through Week 52, and SRI 4 composite response at Week 52 were reported. Reduction of glucocorticoid dose was defined as reduction in average daily oral glucocorticoid dose by at least 50% (relative to baseline dose) or reduction of average daily oral glucocorticoid dose by at least 25% (relative to baseline dose) so that average daily dose is reduced to <=7.5 mg (prednisone or equivalent). Sustained reduction of glucocorticoid dose was defined as achieving an average daily oral glucocorticoid dose reduction between Weeks 24 and 40, and sustaining that reduction through Week 52, in those participants who,at baseline,were receiving oral glucocorticoids. SRI-4 was defined as composite of at least 4-point improvement in SLEDAI-2K score of 0=no symptoms to 105=presence of all defined symptoms with higher scores representing increased disease activity),no worsening in BILAG and no worsening in PGA.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Be male or female

• Has a documented medical history (that is, met at least 1 of the two criteria below) that participant met the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for systemic lupus erythematosus (SLE) at least 3 months prior to first dose of study agent:

1. Met a total of at least 4 SLICC criteria, including at least 1 clinical and at least 1 immunologic;

2. Has a diagnosis of lupus nephritis, confirmed by renal biopsy and at least 1 of the following autoantibodies: antinuclear antibodies (ANA) or anti-double-stranded deoxyribonucleic acid (anti-dsDNA)

• Has a positive test in the medical history and confirmed at screening for at least 1 of the following autoantibodies: antinuclear antibodies, anti-double-stranded deoxyribonucleic acid, and/or anti-Smith

• Has greater than or equal to (>=) 1 British Isles Lupus Assessment Group (BILAG) A and/or >= 2 BILAG B scores observed during screening

• Has a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score >=4 (excluding diffuse non-inflammatory alopecia) or >= 4 joints with pain and signs of inflammation at screening, Week 0, or both

• Has a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score >=6 at screening. Must also have SLEDAI-2K >= 4 for clinical features (excluding headache and laboratory abnormalities) at Week 0

• Cannot be pregnant, nursing, intending to become pregnant, or unwilling to follow contraception or egg/sperm donation guidelines

• Must be receiving stable doses of >=1 protocol-permitted standard of care SLE treatment: oral glucocorticoids, anti-malarials, immunomodulators (methotrexate, azathioprine, 6-mercaptopurine, mycophenolate mofetil, mycophenolic acid)

Exclusion Criteria:

• Has any unstable or progressive SLE manifestation (example: central nervous system lupus, systemic vasculitis, end-stage renal disease, severe or rapidly progressive glomerulonephritis, pulmonary hemorrhage, myocarditis) that may warrant escalation in therapy beyond permitted background medications. Participants requiring renal hemodialysis or peritoneal dialysis are also excluded

• Has other co-existent inflammatory diseases (example: rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease)

• Has a urinary protein to creatinine ratio of greater than (>)4 gram per gram (g/g) per day

• Has an acute or chronic infectious illness (example: human immunodeficiency virus, hepatitis B or C virus, tuberculosis, opportunistic infections)

• Has a history of cancer or lymphoproliferative disease within the last 5 years except for treated and non-recurrent cutaneous basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma

• Has any condition requiring multiple courses of systemic glucocorticoids (example: uncontrolled asthma, chronic obstructive pulmonary disease)

• Has a history of major surgery within the last month

• Has received live virus or bacterial vaccines within 16 weeks prior to first dose of study agent or Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening

• Has previously received ustekinumab

• Has received cyclophosphamide orally within 90 days or intravenously within 180 days of screening

• Has received a single B-cell targeted therapy (e.g. belimumab) within 3 months, >1 previous B-cell targeted therapy within 6 months, or B-cell depleting therapy (example: rituximab) within 12 months of first dose of study agent

• Has received protocol-prohibited oral or biologic immunomodulatory therapy in the last 3 months or less than (<)5 half-lives (whichever is longer) prior to first dose of study agent

• Has received adrenocorticotropic hormone (ACTH) within 1 month prior to first dose of study agent

• Has received epidural, intravenous, intramuscular, intraarticular, intrabursal, intralesional glucocorticoids within 6 weeks of first dose of study agent

• Locally-delivered therapies except for ophthalmic use of cyclosporine A or topical use of nonsteroidal anti inflammatory drugs (NSAIDs), analgesics, or high-potency glucocorticoids (World Health Organization criteria) are prohibited

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group, LLC	Anniston	Alabama	United States	36207
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
3	Achieve Clinical Research, LLC	Vestavia Hills	Alabama	United States	35216
4	Medvin Clinical Research	Covina	California	United States	91722
5	Lugene Eye Institute	Glendale	California	United States	91204
6	C.V. Mehta, MD Medical Corp.	Hemet	California	United States	92543
7	University of California at San Diego	La Jolla	California	United States	92093
8	Advanced Medical Research - Lakewood	Lakewood	California	United States	90712
9	Loma Linda University	Loma Linda	California	United States	92350
10	Loma Linda University Health Care	Loma Linda	California	United States	92357
11	Valerius Medical Group & Research Center	Los Alamitos	California	United States	90720
12	Keck School of Medicine of USC	Los Angeles	California	United States	90033
13	Wallace Rheumatic Study Center	Los Angeles	California	United States	90048
14	East Bay Rheumatology Medical Group	San Leandro	California	United States	94578
15	Westlake Medical Research Clinical Trials	Thousand Oaks	California	United States	91360
16	University Clinical Investigators, Inc	Tustin	California	United States	92780
17	Inland Rheumatology Clinical Trials Inc.	Upland	California	United States	91786
18	University of Colorado	Aurora	Colorado	United States	80045
19	Denver Arthritis Clinic	Denver	Colorado	United States	80230
20	UPMC Lupus Center of Excellence	New Haven	Connecticut	United States	06520
21	Stamford Therapeutics Consortium	Stamford	Connecticut	United States	06905
22	Arthritis and Rheumatic Disease Specialties	Aventura	Florida	United States	33180
23	Bay Area Arthritis and Osteoporosis	Brandon	Florida	United States	33511
24	Centre for Rheumatology, Immunology and Arthritis	Fort Lauderdale	Florida	United States	33309
25	University of Florida	Jacksonville	Florida	United States	32207
26	University of Miami Miller School of Medicine	Miami	Florida	United States	33136-1002
27	New Horizon Research Center	Miami	Florida	United States	33175
28	Rheumatology Associates of Central Florida, PA	Orlando	Florida	United States	32806
29	Omega Research Consultants	Orlando	Florida	United States	32810
30	Millennium Research	Ormond Beach	Florida	United States	32174
31	Integral Rheumatology & Immunology Specialists	Plantation	Florida	United States	33324
32	Clinical Research of West Florida	Tampa	Florida	United States	33603
33	Emory University	Atlanta	Georgia	United States	30303
34	Piedmont Healthcare - Piedmont Hospital	Atlanta	Georgia	United States	30309
35	DeKalb Medical Specialty Center	Decatur	Georgia	United States	30033
36	Rush University Medical Center	Chicago	Illinois	United States	60612
37	University of Chicago	Chicago	Illinois	United States	60637
38	Graves-Gilbert Clinic - Bowling Green	Bowling Green	Kentucky	United States	42101
39	Arthritis and Diabetes Clinic	Monroe	Louisiana	United States	71203
40	The Center for Rheumatology and Bone Research	Wheaton	Maryland	United States	20902
41	June DO, PC.	Lansing	Michigan	United States	48910-8595
42	St Paul Rheumatology PA	Eagan	Minnesota	United States	55121
43	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
44	Oklahoma Medical Research Foundation	Las Vegas	Nevada	United States	89102
45	Innovative Health Research	Las Vegas	Nevada	United States	89128
46	Albuquerque Center for Rheumatology	Albuquerque	New Mexico	United States	87102
47	Biomedical Research Alliance Of New York	Lake Success	New York	United States	10075
48	The Feinstein Institute for Medical Research	Manhasset	New York	United States	11030
49	NYU Center for Musculoskeletal Care	New York	New York	United States	10016
50	Hospital for Special Surgery	New York	New York	United States	10021
51	SUNY Upstate Medical University	Syracuse	New York	United States	13210
52	Joint and Muscle Research Institute	Charlotte	North Carolina	United States	28204
53	DJL Clinical Research, PLLC	Charlotte	North Carolina	United States	28210
54	Duke University Medical Center	Durham	North Carolina	United States	27710
55	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
56	OK Center for Arthritis Therapy & Research, Inc.	Tulsa	Oklahoma	United States	74104
57	Lewis Katz School of Medicine, Temple University	Philadelphia	Pennsylvania	United States	19140
58	Allegheny Rheumatology/Allegheny Singer Research Institute	Wexford	Pennsylvania	United States	15090
59	Columbia Arthritis Center	Columbia	South Carolina	United States	29204
60	West Tennessee Research Institute	Jackson	Tennessee	United States	38305
61	Dr. Ramesh Gupta	Memphis	Tennessee	United States	38119
62	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212-3103
63	Amarillo Center for Clinical Research	Amarillo	Texas	United States	79124
64	Austin Regional Clinic	Austin	Texas	United States	78731
65	Arthritis Centers of Texas	Dallas	Texas	United States	75246
66	Sun Research Institute	San Antonio	Texas	United States	78215
67	UT Health Science Center at San Antonio	San Antonio	Texas	United States	78239
68	University of Washington	Seattle	Washington	United States	98195
69	Rheumatology & Pulmonary Clinic	Beckley	West Virginia	United States	25801
70	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires		Argentina	C1025ABI
71	Instituto Centenario	Buenos Aires		Argentina	C1204AAP
72	Centro Privado de Medicina Familiar	Buenos Aires		Argentina	C1417EYG
73	Framingham Centro Medico	Ciudad De La Plata		Argentina	B1902COS
74	Hospital Italiano de Cordoba	Cordoba		Argentina	X5004BAL
75	Hospital Escuela 'Gral. Jose F. de San Martin'	Corrientes		Argentina	3400
76	CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica	San Juan		Argentina	J5402DIL
77	Centro Medico Privado de Reumatologia	San Miguel de Tucumán		Argentina	T4000AXL
78	MHAT Trimantium	Plovdiv		Bulgaria	4000
79	Diagnostic-Consultative Center (DCC) Aleksandrovska	Sofia		Bulgaria	1431
80	UMHAT 'St. Ivan Rilski'	Sofia		Bulgaria	1612
81	Medical Centre Synexus	Sofia		Bulgaria	1709
82	University of Calgary	Calgary	Alberta	Canada	T2N 4Z6
83	University of Manitoba	Winnipeg	Manitoba	Canada	R3A 1M4
84	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
85	McMaster University	Hamilton		Canada	L8N 3Z5
86	CHU de Québec	Quebec		Canada	G1V-2L9
87	The First Affiliated Hospital of Baotou Medical University	Baotou		China	014010
88	Peking Union Medical College Hospital	Beijing		China	100730
89	West China Hospital, Sichuan University	Chengdu		China	610041
90	Guangdong Provincial People's Hospital	Guangzhou		China	510080
91	Affiliated Hospital of Inner Mongolia Med U	Hohhot		China	10000
92	Shanghai Ruijin Hospital	Shanghai		China	200025
93	Tianjin Medical University General Hospital	Tianjin		China	300052
94	Tongji Hospital of Tongji Medical College of Huangzhong Univ	Wuhan		China	430030
95	The 1st affiliated Hospital of Xi'an Traffic University	Xi'an		China	710061
96	Centro de Investigación en Reumatología y especialidades médicas S.A.S. - CIREEM S.A.S.	Bogotá		Colombia	110221
97	IPS Medicity SAS	Bucaramanga		Colombia
98	Servimed S.A.S	Bucaramanga		Colombia
99	Preventive Care Ltda	Chia		Colombia	250001
100	Clinica Universitaria Bolivariana	Medellin		Colombia	050034
101	Funcentra	Montería		Colombia	230002
102	Charite - Universitatsmedizin Berlin (CCM)	Berlin		Germany	10117
103	Medizinische Hochschule Hannover	Hannover		Germany	30625
104	Rheumazentrum Ruhrgebiet	Herne		Germany	44649
105	Rheumatology Unit	Leipzig		Germany	04103
106	Universitaetsmedizin Mainz	Mainz		Germany	55131
107	Szt, Istvan and Szt. Laszlo	Budapest		Hungary	1097
108	Bekes Megyei Pandy Kalman Korhaz	Gyula		Hungary	5700
109	Leda Private Clinic	Zalaegerszeg		Hungary	H-8900
110	Chiba University Hospital	Chiba		Japan	260-8677
111	National Hospital Organization Chibahigashi National Hospital	Chiba		Japan	260-8712
112	National Hospital Organization Kyushu Medical Center	Fukuoka		Japan	810-8563
113	Fukushima Medical University Hospital	Fukushima		Japan	960-1295
114	Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital	Hiroshima		Japan	730-8619
115	Hospital of the University of Occupational and Enviromental Health	Hukuoka		Japan	807-8555
116	National Hospital Organization Osaka Minami Medical Center	Kawachi-Nagano		Japan	586-8521
117	Kawasaki Rheumatism and Internal Medicine Clinic	Kitakyushu		Japan	807-0856
118	Toho University Medical Center, Ohashi Hospital	Meguro-ku		Japan	153-8515
119	Nagasaki University Hospital	Nagasaki		Japan	852-8501
120	National Hospital Organization Nagoya Medical Center	Nagoya		Japan	460-0001
121	Kitasato University Hospital	Sagamihara		Japan	252-0375
122	Hokkaido University Hospital	Sapporo-shi		Japan	060-8648
123	Sapporo City General Hospital	Sapporo		Japan	060-8604
124	Sasebo Chuo Hospital	Sasebo		Japan	857-1165
125	Tohoku University Hospital	Sendai-shi		Japan	980-8574
126	Keio University Hospital	Shinjuku-ku		Japan	160-8582
127	National Center for Global Health and Medicine	Shinjuku-ku		Japan	162-8655
128	St. Luke's International Hospital	Tokyo		Japan	104-8560
129	Juntendo University Hospital	Tokyo		Japan	113-8431
130	Fujita Health University Hospital	Toyoake		Japan	470-1192
131	National Hospital Organization Yokohama Medical Center	Yokohama		Japan	245-8575
132	Daegu Catholic University Medical Center	Daegu		Korea, Republic of	705-718
133	Chonbuk National Univ Hospital	JeonJu		Korea, Republic of	54907
134	Seoul National University Hospital	Seoul		Korea, Republic of	03080
135	Konkuk University Medical Center	Seoul		Korea, Republic of	05030
136	Ajou University Hospital	Suwon		Korea, Republic of	16499
137	Lietuvos sveikatos mokslų universiteto ligoninė Kauno klinik	Kaunas		Lithuania	LT-50161
138	Klaipeda University Hospital	Klaipeda		Lithuania	LT-92288
139	Vaiku ligonine Vilniaus Universiteto ligon. Santariskiu fil	Vilnius		Lithuania	08406
140	Vilnius University Hospital Santariskiu Clinics	Vilnius		Lithuania	LT-08661
141	Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy	Bydgoszcz		Poland	85-168
142	Nzoz Bif-Med	Bytom		Poland	41-902
143	Centrum Medyczne AMED oddzial w Lodzi	Lodz		Poland	91-363
144	Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie	Lublin		Poland	20-954
145	Twoja Przychodnia - Centrum Medyczne Nowa Sol	Nowa Sól		Poland	67-100
146	Centrum Medyczne Medens S.C. Grupowa Praktyka Lekarska	Sonoswiec		Poland	41-200
147	Centrum Medyczne Pratia Tychy	Tychy		Poland	43-100
148	Centrum Medyczne Pratia Warszawa	Warszawa		Poland	01-868
149	Reumatika-Centrum Reumatologii, NZOZ	Warszawa		Poland	02-691
150	Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego	Wroclaw		Poland	50-556
151	Instituto Portugues de Reumatologia	Lisboa		Portugal	1050-034
152	Hospital Curry Cabral-Centro Hospital Lisboa Central	Lisboa		Portugal	1069-166
153	Hospital da Luz	Lisboa		Portugal	1500-650
154	ULSAM, EPE - Hospital Conde de Bertiandos	Ponte de Lima		Portugal	4990-041
155	C.H. de Vila Nova de Gaia/Espinho	Vila Nova de Gaia		Portugal	4434-502
156	Regional Clinical Hospital for War Veterans	Kemerovo		Russian Federation	650000
157	LLL Medical Center Revma-Med	Kemerovo		Russian Federation	650070
158	Clinical Diagnostic Center 'Ultramed'	Omsk		Russian Federation	644024
159	Leningrad region clinical hospital	Saint-Petersburg		Russian Federation	194291
160	City Clinical Hospital #31	St. Petersburg		Russian Federation	197110
161	Northen-Western State Medical University n.a. I.I. Mechnikov	St.-Petersburg		Russian Federation	191015
162	Ulyanovsk Regional Clinical Hospital	Ulyanovsk		Russian Federation	432063
163	Clinical Emergency Hospital n.a. N.V. Solovyev	Yaroslavl		Russian Federation	150003
164	Institute of Rheumatology Belgrade	Belgrade		Serbia	11000
165	Institute of Rheumatology	Belgrade		Serbia	11000
166	Military Medical Academy	Belgrade		Serbia	11000
167	Clinical Hospital Center Bezanijska Kosa	Belgrade		Serbia	11080
168	University Clinical Center Kragujevac	Kragujevac		Serbia	34000
169	Institute for Treatment and Rehabilitation Niska Banja	Niska Banja		Serbia	18205
170	Clinical Center of Vojvodina	Vojvodina		Serbia	21000
171	Panorama Medical Centre	Cape Town		South Africa	7500
172	Excellentis Clinical trial Consultants	George		South Africa	6529
173	Clinical Research Unit, University of Pretoria	Pretoria		South Africa	0002
174	Winelands Medical Research Centre	Stellenbosch		South Africa	7613
175	Hosp. Univ. Vall D Hebron	Barcelona		Spain	8035
176	Hosp. Univ. de Basurto	Bilbao		Spain	48013
177	Hosp. Reina Sofia	Cordoba		Spain	14004
178	Hosp. Clinico San Carlos	Madrid		Spain	28040
179	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
180	Hosp. Regional Univ. de Malaga	Málaga		Spain	29009
181	Hosp. Univ. Infanta Sofia	San Sebastián de los Reyes		Spain	28702
182	Hosp. Infanta Luisa	Sevilla		Spain	41010
183	Hosp. Do Meixoeiro	Vigo -Pontevedra		Spain	36214
184	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
185	Chang Gung Memorial Hospital	Kwei-san Hsiang		Taiwan	333
186	Chung Shan Medical University Hospital	Taichung		Taiwan	402
187	China Medical University Hospital	Taichung		Taiwan	40447
188	National Taiwan University Hospital	Taipei		Taiwan	10043
189	Cathay General Hospital	Taipei		Taiwan	10601
190	Taipei Medical University	Taipei		Taiwan	11031
191	Taipei Veterans General Hospital	Taipei		Taiwan	112
192	Phramongkutklao Hospital and Medical College	Bangkok		Thailand	10400
193	Rajavhiti Hospital	Bangkok		Thailand	10400
194	Ramathibodi Hospital	Bangkok		Thailand	10400
195	Siriraj Hospital	Bangkok		Thailand	10700
196	Songklanagarind hospital	Hat Yai		Thailand	90110
197	Chiang Mai University	Muang		Thailand	50200
198	Mechnikov Inst, Miska bagatoprofilna likarnia #18	Kharkiv		Ukraine	61029
199	Kyiv City Clinical Hospital #3	Kyiv		Ukraine	02125
200	Kyivska oblasna klinichna likarnia	Kyiv		Ukraine	4107
201	Odeska oblasna klinichna likarnia	Odesa		Ukraine	65025
202	Multidisciplinary Medical Center of Odessa National Medical University	Odessa		Ukraine	65026
203	MNPE 'Vinnytsia Regional Clinical Hospital named after M.I. Pyrogov of Vinnytsia Regional Council'	Vinnytsia		Ukraine	21018
204	Naukovo-doslidnyi inst. Reabilit. Pyrogova [Revmatologichne]	Vinnytsia		Ukraine	21029

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol - Jan 23, 2019
• Statistical Analysis Plan - Sep 23, 2020

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03517722
• Other Study ID Numbers: CR108440; 2017-001489-53; CNTO1275SLE3001
• First Posted: May 7, 2018
• Last Update Posted: Mar 9, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic; Ustekinumab

Study Results

Participant Flow

Pre-assignment Detail	Participants received study drug up to Week 113, but were assessed for safety up to Week 130 (that is, after study termination).

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
Period Title: Double Blind Period: Week 0-52
STARTED	208	308
Treated	208	307
COMPLETED	105	153
NOT COMPLETED	103	155
Period Title: Double Blind Period: Week 0-52
STARTED	88	137
COMPLETED	0	0
NOT COMPLETED	88	137

Baseline Characteristics

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab	Total
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.	Total of all reporting groups
Overall Participants	208	308	516
Age (Count of Participants)
<=18 years	3 1.4%	1 0.3%	4 0.8%
Between 18 and 65 years	191 91.8%	294 95.5%	485 94%
>=65 years	14 6.7%	13 4.2%	27 5.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.5 (12.31)	42.9 (11.38)	43.5 (11.78)
Sex: Female, Male (Count of Participants)
Female	191 91.8%	291 94.5%	482 93.4%
Male	17 8.2%	17 5.5%	34 6.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	34 16.3%	45 14.6%	79 15.3%
Not Hispanic or Latino	172 82.7%	263 85.4%	435 84.3%
Unknown or Not Reported	2 1%	0 0%	2 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1%	7 2.3%	9 1.7%
Asian	46 22.1%	57 18.5%	103 20%
Native Hawaiian or Other Pacific Islander	0 0%	2 0.6%	2 0.4%
Black or African American	18 8.7%	24 7.8%	42 8.1%
White	136 65.4%	208 67.5%	344 66.7%
More than one race	1 0.5%	0 0%	1 0.2%
Unknown or Not Reported	5 2.4%	10 3.2%	15 2.9%
Region of Enrollment (Count of Participants)
ARGENTINA	15 7.2%	13 4.2%	28 5.4%
BULGARIA	11 5.3%	16 5.2%	27 5.2%
CANADA	0 0%	2 0.6%	2 0.4%
CHINA	4 1.9%	4 1.3%	8 1.6%
COLOMBIA	7 3.4%	10 3.2%	17 3.3%
GERMANY	9 4.3%	10 3.2%	19 3.7%
HUNGARY	3 1.4%	11 3.6%	14 2.7%
JAPAN	21 10.1%	25 8.1%	46 8.9%
LITHUANIA	10 4.8%	11 3.6%	21 4.1%
POLAND	17 8.2%	21 6.8%	38 7.4%
PORTUGAL	0 0%	1 0.3%	1 0.2%
RUSSIAN FEDERATION	11 5.3%	19 6.2%	30 5.8%
SERBIA	14 6.7%	28 9.1%	42 8.1%
SOUTH AFRICA	4 1.9%	8 2.6%	12 2.3%
SOUTH KOREA	0 0%	5 1.6%	5 1%
SPAIN	4 1.9%	6 1.9%	10 1.9%
TAIWAN	11 5.3%	14 4.5%	25 4.8%
THAILAND	7 3.4%	5 1.6%	12 2.3%
UKRAINE	8 3.8%	22 7.1%	30 5.8%
UNITED STATES	52 25%	77 25%	129 25%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Composite Response at Week 52
Description	SRI-4 response:>=4-point reduction in SLEDAI-2K total score, no British Isles Lupus Assessment Group (BILAG) A (severe disease) and no more than 1 new BILAG B (moderate disease) domain score and no worsening (<10 % increase)from baseline in Physician's Global Assessment(PGA).SLEDAI measures disease activity in 9 organ systems,higher scores=more severe disease activity.Each organ system measured as either absent/present within last 30 days and weighted score across systems was utilized to calculate total SLEDAI score(range:0=no symptoms to 105=presence of all defined symptoms). Improvement is defined as reduction in SLEDAI score (BILAG) Index: assessing clinical signs, symptoms,or laboratory parameters related to SLE,divided into 9 domains. Each domain can range from A=new domain activity, B=worse domain activity, C=same domain activity, D=improving domain activity to E=absence of domain activity. PGA assesses disease activity on visual analogue scale from very well(0)-very poor(10).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The projected full analysis set (FAS) was defined as those participants (participants who received at least 1 dose [partial or complete,intravenous [IV] or subcutaneous [SC] of study agent) who should have had a given visit based upon their latest scheduled study visit. Participants were set to non-responders if they met treatment failure (TF) or had data missing.

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
Measure Participants	116	173
Number [percentage of participants]	56.0 26.9%	43.9 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo to Ustekinumab, Ustekinumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.042
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; 0.4 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to First Flare
Description	Time to flare is defined as the time (in days) post baseline when the first flare occurs. It was calculated with flare defined as either 1 or more BILAG A (severe disease activity) or 2 or more new BILAG B (moderate disease activity) domain scores relative to baseline. BILAG was defined as a measure of alterations or intensification to therapy consisting of 97 questions in 9 domains. Each domain can range from A=new domain activity, B=worse domain activity, C=same domain activity, D=improving domain activity to E=absence of domain activity. BILAG A flare was defined as at least 1 new BILAG A scores. BILAG B flare was defined as at least 2 new BILAG B scores.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Analysis population is projected FAS. Participants were set to have flare if they met TF criteria (exceeded baseline dose of permitted SLE medications, initiated a new permitted SLE medication, initiated new protocol-prohibited medication or discontinued study agent for any reason prior to Week 52).

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
Measure Participants	116	173
Time to First BILAG Flare	200.4 (121.27)	204.7 (107.82)
Time to First BILAG A Flare	201.4 (122.83)	203.1 (108.37)
Time to First BILAG B Flare	218.1 (125.00)	208.7 (107.51)

3. Secondary Outcome

Title	Percentage of Participants With an SRI-4 Composite Response at Week 24
Description	SRI-4 response:>=4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no BILAG A (severe disease) and no more than 1 new BILAG B (moderate disease) domain score and no worsening (<10 % increase)from baseline in PGA.SLEDAI measures disease activity in 9 organ systems, higher scores=more severe disease activity. Each organ system measured as either absent/present within last 30 days and weighted score across systems was utilized to calculate total SLEDAI score(range:0=no symptoms to 105=presence of all defined symptoms). Improvement is defined as reduction in SLEDAI score (BILAG) Index: assessing clinical signs, symptoms,or laboratory parameters related to SLE,divided into 9 domains. Each domain can range from A=new domain activity, B=worse domain activity, C=same domain activity, D=improving domain activity to E=absence of domain activity. PGA assesses disease activity on visual analogue scale from very well(0)-very poor(10).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Population analyzed included projected analysis set among participants who had or should have had a Week 24 visit based upon their last scheduled visit.

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
Measure Participants	116	173
Number [percentage of participants]	56 26.9%	45.7 14.8%

4. Secondary Outcome

Title	Percentage of Participants With 50 Percent (%) Improvement in Joints With Pain and Signs of Inflammation (Active Joints) at Week 52
Description	The percentage of participants who achieved at least 50% improvement from baseline in number of joints with pain and signs of inflammation at Week 52 for participants with at least 4 joints with pain and signs of inflammation at baseline were reported.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Analysis population is projected analysis set which included participants who had at least 4 joints with pain and signs of inflammation at baseline. Here, 'N' (number of participants analyzed) refers to participants evaluable included participants who had or should have had a Week 52 visit based upon their last scheduled visit and the date of trial termination.

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
Measure Participants	101	153
Number [percentage of participants]	66.3 31.9%	64.7 21%

5. Secondary Outcome

Title	Percentage of Participants Receiving Glucocorticoid at Baseline Who Achieved Change in Glucocorticoid Dose by Week 40 and Sustain That Change Through Week 52
Description	Reduction of glucocorticoid dose was defined as a reduction in average daily oral glucocorticoid dose by at least 50% (relative to the baseline dose) or reduction of average daily oral glucocorticoid dose by at least 25% (relative to the baseline dose) so that the average daily dose was reduced to less than or equal to (<=) 7.5 milligram (mg) (prednisone or equivalent). Sustained reduction of glucocorticoid dose was defined as achieving an average daily oral glucocorticoid dose reduction between Weeks 24 and 40, and sustaining that reduction through Week 52, in those participants who, at baseline, were receiving oral glucocorticoids.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Analysis population is projected analysis set which included participants who received glucocorticoids at baseline. Here, 'N' (number of participants analyzed) refers to participants evaluable including participants who had or should have had a Week 52 visit based upon their last scheduled visit and the date of trial termination. Participants were set to non-responders if they met TF or had data missing.

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
Measure Participants	92	140
Number [percentage of participants]	29.3 14.1%	44.3 14.4%

6. Secondary Outcome

Title	Percentage of Participants With at Least a 50% Improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 52
Description	Percentage of participants achieving at least 50% improvement in CLASI activity score at Week 52 reported in participants with a CLASI activity score of 4 or greater at baseline. The CLASI is an instrument to assess the disease activity and damage caused to the skin for cutaneous lupus erythematosus participants with or without systemic involvement. The CLASI activity score ranges from 0-70 with lower score being improved. Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss, and non-scarring alopecia.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Analysis population is projected FAS. Here, 'N' (number of participants analyzed) refers to participants who had or should have had a Week 52 visit based upon their last scheduled visit and the date of trial termination and with a CLASI activity score of 4 or greater at baseline. Participants were set to non-responders if they met TF or had data missing.

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
Measure Participants	93	135
Number [percentage of participants]	55.9 26.9%	40.7 13.2%

7. Secondary Outcome

Title	Percentage of Participants Receiving Glucocorticoid at Baseline Who Achieved Change in Glucocorticoid Dose by Week 40, Sustained That Change Through Week 52, and Achieved an SRI-4 Composite Response at Week 52
Description	Percentage of participants with reduction in glucocorticoid dose by Week 40, its sustenance through Week 52, and SRI 4 composite response at Week 52 were reported. Reduction of glucocorticoid dose was defined as reduction in average daily oral glucocorticoid dose by at least 50% (relative to baseline dose) or reduction of average daily oral glucocorticoid dose by at least 25% (relative to baseline dose) so that average daily dose is reduced to <=7.5 mg (prednisone or equivalent). Sustained reduction of glucocorticoid dose was defined as achieving an average daily oral glucocorticoid dose reduction between Weeks 24 and 40, and sustaining that reduction through Week 52, in those participants who,at baseline,were receiving oral glucocorticoids. SRI-4 was defined as composite of at least 4-point improvement in SLEDAI-2K score of 0=no symptoms to 105=presence of all defined symptoms with higher scores representing increased disease activity),no worsening in BILAG and no worsening in PGA.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Analysis population is projected analysis set which included participants who received glucocorticoids at baseline. Here, 'N' (number of participants analyzed) refers to participants evaluable included participants who had or should have had a Week 52 visit based upon their last scheduled visit and the date of trial termination. Participants were set to non-responders if they met TF or had data missing.

Arm/Group Title	Placebo to Ustekinumab	Ustekinumab
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period crossed over to receive ustekinumab 90 mg SC q8w through Week 113.	Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to {<=} 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the open-label extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
Measure Participants	92	140
Number [percentage of participants]	23.9 11.5%	30.0 9.7%

Adverse Events

Time Frame	Up to Week 130
Adverse Event Reporting Description	Safety analysis set included participants who were randomized, received at least 1 dose (partial or complete, intravenous or subcutaneous) of ustekinumab or placebo, and contributed any safety data after the start of study treatment. Participants received study drug up to Week 113, but were assessed for safety up to Week 130 (that is, after study termination). Participants were analyzed according to the actual treatment received.
Arm/Group Title	Placebo (Prior to Entering (Long Term Extension [LTE])		Placebo to Ustekinumab (After Entering LTE)		Ustekinumab (Through Week 113)
Arm/Group Description	Participants received matching placebo to ustekinumab intravenously (IV) 6 milligrams per kilogram (mg/kg) IV based on body weight at Week 0 followed by matching placebo to ustekinumab subcutaneously (SC) 90 mg at Week 8 and every 8 weeks (q8w) thereafter through Week 48 during double-blind period.		Participants who entered the open-label extension period at Week 52 crossed over to receive ustekinumab 90 mg SC q8w through Week 113.		Participants received ustekinumab 6 mg/kg IV based on body weight (ustekinumab 260 mg [weight less than or equal to (<=) 55 kg]; ustekinumab 390 mg [weight greater than {>} 55 kg and <= 85 kg] at Week 0 followed by ustekinumab 90 mg SC at Week 8 and q8w thereafter through Week 48 during double-blind period. At Week 52, participants who entered the extension period continued to receive ustekinumab 90 mg SC q8w through Week 113.
All Cause Mortality
	Placebo (Prior to Entering (Long Term Extension [LTE])		Placebo to Ustekinumab (After Entering LTE)		Ustekinumab (Through Week 113)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/208 (0.5%)		0/88 (0%)		5/307 (1.6%)
Serious Adverse Events
	Placebo (Prior to Entering (Long Term Extension [LTE])		Placebo to Ustekinumab (After Entering LTE)		Ustekinumab (Through Week 113)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/208 (13.5%)		5/88 (5.7%)		44/307 (14.3%)
Blood and lymphatic system disorders
Thrombocytopenia	2/208 (1%)		0/88 (0%)		1/307 (0.3%)
Cardiac disorders
Acute Myocardial Infarction	2/208 (1%)		1/88 (1.1%)		0/307 (0%)
Bradycardia	0/208 (0%)		1/88 (1.1%)		0/307 (0%)
Cardiac Failure	0/208 (0%)		0/88 (0%)		2/307 (0.7%)
Pericardial Effusion	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Eye disorders
Retinal Detachment	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Visual Impairment	0/208 (0%)		1/88 (1.1%)		0/307 (0%)
Gastrointestinal disorders
Abdominal Hernia	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Abdominal Pain	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Colitis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Gastritis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Pancreatitis Acute	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Small Intestinal Obstruction	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Hepatobiliary disorders
Hepatorenal Syndrome	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Infections and infestations
Bronchitis	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Covid-19	0/208 (0%)		0/88 (0%)		4/307 (1.3%)
Diverticulitis	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Endocarditis Staphylococcal	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Gastroenteritis	0/208 (0%)		0/88 (0%)		2/307 (0.7%)
Herpes Zoster	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Infected Bite	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Nosocomial Infection	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Pneumonia	1/208 (0.5%)		0/88 (0%)		4/307 (1.3%)
Pulmonary Tuberculosis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Sepsis	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Tonsillitis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Urinary Tract Infection	2/208 (1%)		0/88 (0%)		1/307 (0.3%)
Urosepsis	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Viral Infection	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Vulval Cellulitis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Injury, poisoning and procedural complications
Fall	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Implantation Complication	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Infusion Related Reaction	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Patella Fracture	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Post Procedural Fever	0/208 (0%)		1/88 (1.1%)		0/307 (0%)
Post Procedural Haemorrhage	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Splenic Rupture	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Ulna Fracture	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Metabolism and nutrition disorders
Electrolyte Imbalance	1/208 (0.5%)		0/88 (0%)		1/307 (0.3%)
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Osteonecrosis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Systemic Lupus Erythematosus	4/208 (1.9%)		0/88 (0%)		2/307 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acoustic Neuroma	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Diffuse Large B-Cell Lymphoma	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Gastric Cancer	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Nervous system disorders
Amnesia	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Embolic Stroke	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Facial Paralysis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Haemorrhagic Stroke	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Neuropsychiatric Lupus	0/208 (0%)		0/88 (0%)		2/307 (0.7%)
Seizure	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Pregnancy, puerperium and perinatal conditions
Hyperemesis Gravidarum	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Renal and urinary disorders
Haematuria	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Hydronephrosis	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Lupus Nephritis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Nephritic Syndrome	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Nephrolithiasis	0/208 (0%)		0/88 (0%)		2/307 (0.7%)
Neurogenic Bladder	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Renal Colic	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Ovarian Cyst	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	0/208 (0%)		0/88 (0%)		2/307 (0.7%)
Lupus Pleurisy	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Pleural Effusion	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Pneumonitis	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Pulmonary Hypertension	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Respiratory Failure	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Skin and subcutaneous tissue disorders
Dermal Cyst	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Hypersensitivity Vasculitis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Pemphigoid	1/208 (0.5%)		0/88 (0%)		0/307 (0%)
Toxic Epidermal Necrolysis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Vascular disorders
Aortic Aneurysm	0/208 (0%)		1/88 (1.1%)		0/307 (0%)
Deep Vein Thrombosis	0/208 (0%)		1/88 (1.1%)		0/307 (0%)
Hypotension	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Hypovolaemic Shock	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Lupus Vasculitis	0/208 (0%)		0/88 (0%)		1/307 (0.3%)
Other (Not Including Serious) Adverse Events
	Placebo (Prior to Entering (Long Term Extension [LTE])		Placebo to Ustekinumab (After Entering LTE)		Ustekinumab (Through Week 113)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/208 (28.8%)		3/88 (3.4%)		79/307 (25.7%)
Infections and infestations
Nasopharyngitis	19/208 (9.1%)		2/88 (2.3%)		24/307 (7.8%)
Upper Respiratory Tract Infection	17/208 (8.2%)		0/88 (0%)		25/307 (8.1%)
Urinary Tract Infection	20/208 (9.6%)		0/88 (0%)		26/307 (8.5%)
Nervous system disorders
Headache	14/208 (6.7%)		1/88 (1.1%)		19/307 (6.2%)

Limitations/Caveats

Due to study termination, the open-label extension phase didn't reach the planned duration till Week 176. However, participants were assessed for safety up to Week 130 (that is, after study termination) and received study drug up to Week 113.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation.