Back to resultsA Phase 2a, Efficacy and Safety Study of Ustekinumab in Systemic Lupus Erythematosus
Primary Purpose
Lupus Erythematosus, Systemic
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ustekinumab IV
Placebo Infusion
Placebo SC
Ustekinumab SC
Concomitant Medication
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Erythematosus, Systemic focused on measuring Systemic Lupus Erythematosus, Ustekinumab
Eligibility Criteria
Inclusion Criteria:
- Subjects must have documented medical history to meet SLICC classification criteria for SLE for a minimum of 3 months prior to first dose
- At least 1 well-documented (subject file, referring physician letter, or laboratory result), unequivocally positive, documented test for autoantibodies in medical history including either of the following: ANA, and/or anti-dsDNA antibodies, and/or anti-Smith antibodies
- At least 1 unequivocally positive autoantibody test including ANA and/or anti-dsDNA antibodies and/or anti-Smith antibodies detected during screening
- At least 1 BILAG A and/or 2 BILAG B domain scores observed during screening prior to first administration of study agent
- Demonstrate active disease based on SLEDAI-2K score greater than or equal to (>=) 6 observed during screening and assessed approximately 2 to 6 weeks prior to randomization. Must also have SLEDAI-2K score >= 4 for clinical features (ie, SLEDAI excluding laboratory results) at Week 0 prior to the first administration of study agent
Exclusion Criteria:
- Have other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), RA/lupus overlap, psoriasis or active Lyme disease
- Are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 4 months after receiving the last administration of study agent
- Have received systemic or topical cream/ointment preparations of cyclosporine A or other systemic immunomodulatory agents other than those described in inclusion criteria within the past 3 months prior to first administration of study agent
- Have received a single B cell targeting agent within 3 months prior to first study agent administration; or received more than 1 previous B cell targeting therapy including belimumab or epratuzamab within 6 months prior to first administration of the study agent; or received B cell depleting therapy (eg, rituximab) within 12 months prior to first administration of the study agent or have evidence of continued B-cell depletion following such therapy
- Have ever received ustekinumab
- Participant has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin that has been treated with no evidence of recurrence for at least 3 months before the first study agent administration and carcinoma in situ of the cervix that has been surgically cured)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Ustekinumab plus Concomitant Medication
Placebo followed by Ustekinumab plus Concomitant Medication
Arm Description
Participants will receive weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0 followed by ustekinumab 90 mg subcutaneously (SC) every 8 weeks (q8w) up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up.
Participants will receive placebo intravenously at Week 0 followed by placebo subcutaneously at Weeks 8 and 16. At week 24 participants will receive ustekinumab SC q8w up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up.
Outcomes
Primary Outcome Measures
Percentage of Participants With a Systemic Lupus Erythematosus Responder Index (SRI-4) Composite Response (CR) at Week 24
SRI-4 response was defined as greater than or equal to 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA). Composite response is defined as SRI-4 response in participants who do not meet treatment failure criteria. SLEDAI-2K assessment consists of 24 items with total score of 0 to 105, with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale = from very well (0)-very poor (10).
Secondary Outcome Measures
Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) Score at Week 24
The SLEDAI-2K is an established, validated SLE activity index. It is based on the presence of 24 features in 9 organ systems and measures disease activity in SLE patients in the previous 30 days. It is weighted according to the feature. Features are scored by the assessing physician if present within the last 30 days with more severe features having higher scores, and then simply added to determine the total SLEDAI 2K score, which ranges from 0 to 105, with higher scores representing increased disease activity.
Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Score at Week 24
PGA was recorded on a visual analogue scale (VAS; 0.0 to 10.0 centimeter [cm]). The scale for the physician's assessment ranges for 'no lupus activity' (0.0) to 'extremely active lupus' (10.0).
Number of Participants With BILAG-based Combined Lupus Assessment (BICLA) Response at Week 24
BICLA response defined as participants meeting following criteria: 1. BILAG improvement (all BILAG A scores at baseline improved to either B, C or D and all BILAG B scores at baseline improved to C or D and no worsening in disease activity defined as no new BILAG A scores and <= 1 new BILAG B score) and 2. no worsening of total SLEDAI-2K from baseline 3. < 1 cm increase in PGA and 4. no treatment failure criteria met. BILAG: assesses disease extent, severity (range: A [severe] to E [no disease]). SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). PGA: assesses worsening in participant's general health status (0.0= 'no lupus activity' to 10.0 = 'extremely active lupus').
Change From Baseline in Number of Joints With Pain and Signs of Inflammation at Week 24
Change from baseline in number of joints (active joint) with pain and signs of inflammation (tenderness, swelling or effusion) for participants with at least 2 affected joints at baseline were reported. An active joint is defined as a joint with pain and signs of inflammation (e.g., tenderness, swelling or effusion).
Full Information
NCT ID
NCT02349061
First Posted
January 23, 2015
Last Updated
March 11, 2020
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02349061
Brief Title
A Phase 2a, Efficacy and Safety Study of Ustekinumab in Systemic Lupus Erythematosus
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study of Ustekinumab in Subjects With Active Systemic Lupus Erythematosus
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
October 15, 2015 (Actual)
Primary Completion Date
May 15, 2017 (Actual)
Study Completion Date
March 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of ustekinumab as measured by a reduction in disease activity for subjects with active Active Systemic Lupus Erythematosus (SLE - chronic disorder of connective tissue in which there can be skin rash, arthritis, kidney problems, and anemia, among other problems).
Detailed Description
A multicenter (more than one medical research center involved in study), randomized (study drug assigned by chance), double-blind (neither the Investigator nor the participant know about the study drug), placebo-controlled, proof-of-concept study of ustekinumab in participants with active systemic lupus erythematosus. Participants will be screened to achieve all inclusion criteria and none exclusion criteria and will then receive either ustekinumab or placebo along with concomitant background medicine. Participants will be primarily assessed for response using the Systemic Lupus Erythematosus Response Index 2000 (SRI-4). Participants' safety will be assessed throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Systemic
Keywords
Systemic Lupus Erythematosus, Ustekinumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ustekinumab plus Concomitant Medication
Arm Type
Experimental
Arm Description
Participants will receive weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0 followed by ustekinumab 90 mg subcutaneously (SC) every 8 weeks (q8w) up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up.
Arm Title
Placebo followed by Ustekinumab plus Concomitant Medication
Arm Type
Experimental
Arm Description
Participants will receive placebo intravenously at Week 0 followed by placebo subcutaneously at Weeks 8 and 16. At week 24 participants will receive ustekinumab SC q8w up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab IV
Other Intervention Name(s)
STELARA
Intervention Description
Weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0.
Intervention Type
Drug
Intervention Name(s)
Placebo Infusion
Intervention Description
Placebo intravenously at Week 0.
Intervention Type
Drug
Intervention Name(s)
Placebo SC
Intervention Description
Placebo subcutaneously at Weeks 8 and 16.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab SC
Intervention Description
Ustekinumab 90 mg subcutaneously every 8 weeks up to Week 40 and up to Week 104 in study extension (for eligible participants)
Intervention Type
Other
Intervention Name(s)
Concomitant Medication
Intervention Description
Concomitant treatment (mycophenolate, azathioprine/6-mercaptopurine, methotrexate, hydroxychloroquine and/or chloroquine, oral corticosteroids, NSAIDs, antihypertensive medications, and topical medications) through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48.
Primary Outcome Measure Information:
Title
Percentage of Participants With a Systemic Lupus Erythematosus Responder Index (SRI-4) Composite Response (CR) at Week 24
Description
SRI-4 response was defined as greater than or equal to 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA). Composite response is defined as SRI-4 response in participants who do not meet treatment failure criteria. SLEDAI-2K assessment consists of 24 items with total score of 0 to 105, with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale = from very well (0)-very poor (10).
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) Score at Week 24
Description
The SLEDAI-2K is an established, validated SLE activity index. It is based on the presence of 24 features in 9 organ systems and measures disease activity in SLE patients in the previous 30 days. It is weighted according to the feature. Features are scored by the assessing physician if present within the last 30 days with more severe features having higher scores, and then simply added to determine the total SLEDAI 2K score, which ranges from 0 to 105, with higher scores representing increased disease activity.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Score at Week 24
Description
PGA was recorded on a visual analogue scale (VAS; 0.0 to 10.0 centimeter [cm]). The scale for the physician's assessment ranges for 'no lupus activity' (0.0) to 'extremely active lupus' (10.0).
Time Frame
Baseline, Week 24
Title
Number of Participants With BILAG-based Combined Lupus Assessment (BICLA) Response at Week 24
Description
BICLA response defined as participants meeting following criteria: 1. BILAG improvement (all BILAG A scores at baseline improved to either B, C or D and all BILAG B scores at baseline improved to C or D and no worsening in disease activity defined as no new BILAG A scores and <= 1 new BILAG B score) and 2. no worsening of total SLEDAI-2K from baseline 3. < 1 cm increase in PGA and 4. no treatment failure criteria met. BILAG: assesses disease extent, severity (range: A [severe] to E [no disease]). SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). PGA: assesses worsening in participant's general health status (0.0= 'no lupus activity' to 10.0 = 'extremely active lupus').
Time Frame
Week 24
Title
Change From Baseline in Number of Joints With Pain and Signs of Inflammation at Week 24
Description
Change from baseline in number of joints (active joint) with pain and signs of inflammation (tenderness, swelling or effusion) for participants with at least 2 affected joints at baseline were reported. An active joint is defined as a joint with pain and signs of inflammation (e.g., tenderness, swelling or effusion).
Time Frame
Baseline, Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must have documented medical history to meet SLICC classification criteria for SLE for a minimum of 3 months prior to first dose
At least 1 well-documented (subject file, referring physician letter, or laboratory result), unequivocally positive, documented test for autoantibodies in medical history including either of the following: ANA, and/or anti-dsDNA antibodies, and/or anti-Smith antibodies
At least 1 unequivocally positive autoantibody test including ANA and/or anti-dsDNA antibodies and/or anti-Smith antibodies detected during screening
At least 1 BILAG A and/or 2 BILAG B domain scores observed during screening prior to first administration of study agent
Demonstrate active disease based on SLEDAI-2K score greater than or equal to (>=) 6 observed during screening and assessed approximately 2 to 6 weeks prior to randomization. Must also have SLEDAI-2K score >= 4 for clinical features (ie, SLEDAI excluding laboratory results) at Week 0 prior to the first administration of study agent
Exclusion Criteria:
Have other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), RA/lupus overlap, psoriasis or active Lyme disease
Are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 4 months after receiving the last administration of study agent
Have received systemic or topical cream/ointment preparations of cyclosporine A or other systemic immunomodulatory agents other than those described in inclusion criteria within the past 3 months prior to first administration of study agent
Have received a single B cell targeting agent within 3 months prior to first study agent administration; or received more than 1 previous B cell targeting therapy including belimumab or epratuzamab within 6 months prior to first administration of the study agent; or received B cell depleting therapy (eg, rituximab) within 12 months prior to first administration of the study agent or have evidence of continued B-cell depletion following such therapy
Have ever received ustekinumab
Participant has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin that has been treated with no evidence of recurrence for at least 3 months before the first study agent administration and carcinoma in situ of the cervix that has been surgically cured)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Huntsville
State/Province
Alabama
Country
United States
City
Beverly Hills
State/Province
California
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Lansing
State/Province
Michigan
Country
United States
City
Manhasset
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Syracuse
State/Province
New York
Country
United States
City
Tulsa
State/Province
Oklahoma
Country
United States
City
Duncansville
State/Province
Pennsylvania
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Jackson
State/Province
Tennessee
Country
United States
City
Buenos Aires
Country
Argentina
City
Ciudad De San Miguel De Tucuman
Country
Argentina
City
San Juan
Country
Argentina
City
Adelaide
Country
Australia
City
Camberwell
Country
Australia
City
Heidelberg
Country
Australia
City
Liverpool
Country
Australia
City
Nedlands
Country
Australia
City
Berlin
Country
Germany
City
Frankfurt
Country
Germany
City
Koeln
Country
Germany
City
Budapest
Country
Hungary
City
Debrecen
Country
Hungary
City
Szeged
Country
Hungary
City
Zalaegerszeg
Country
Hungary
City
Chihuahua
Country
Mexico
City
Guadalajara
Country
Mexico
City
Leon
Country
Mexico
City
Mexico
Country
Mexico
City
Bydgoszcz
Country
Poland
City
Poznan
Country
Poland
City
Szczecin
Country
Poland
City
Wroclaw
Country
Poland
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
City
Málaga
Country
Spain
City
Santiago de Compostela
Country
Spain
City
Sevilla
Country
Spain
City
Kaohsiung
Country
Taiwan
City
Taichung City
Country
Taiwan
City
Taichung
Country
Taiwan
City
Taoyuan
Country
Taiwan
12. IPD Sharing Statement
Citations:
PubMed Identifier
34853089
Citation
van Vollenhoven RF, Hahn BH, Tsokos GC, Lipsky P, Gordon RM, Fei K, Lo KH, Chevrier M, Rose S, Berry P, Yao Z, Karyekar CS, Zuraw Q. Efficacy and Safety of Ustekinumab in Patients With Active Systemic Lupus Erythematosus: Results of a Phase II Open-label Extension Study. J Rheumatol. 2022 Apr;49(4):380-387. doi: 10.3899/jrheum.210805. Epub 2021 Dec 1.
Results Reference
derived
PubMed Identifier
33687069
Citation
Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
Results Reference
derived
PubMed Identifier
33010188
Citation
Cesaroni M, Seridi L, Loza MJ, Schreiter J, Sweet K, Franks C, Ma K, Orillion A, Campbell K, M Gordon R, Branigan P, Lipsky P, van Vollenhoven R, Hahn BH, Tsokos GC, Chevrier M, Rose S, Baribaud F, Jordan J. Suppression of Serum Interferon-gamma Levels as a Potential Measure of Response to Ustekinumab Treatment in Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2021 Mar;73(3):472-477. doi: 10.1002/art.41547. Epub 2021 Feb 1.
Results Reference
derived
PubMed Identifier
31769212
Citation
van Vollenhoven RF, Hahn BH, Tsokos GC, Lipsky P, Fei K, Gordon RM, Gregan I, Lo KH, Chevrier M, Rose S. Maintenance of Efficacy and Safety of Ustekinumab Through One Year in a Phase II Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Patients With Active Systemic Lupus Erythematosus. Arthritis Rheumatol. 2020 May;72(5):761-768. doi: 10.1002/art.41179. Epub 2020 Apr 1.
Results Reference
derived
PubMed Identifier
30249507
Citation
van Vollenhoven RF, Hahn BH, Tsokos GC, Wagner CL, Lipsky P, Touma Z, Werth VP, Gordon RM, Zhou B, Hsu B, Chevrier M, Triebel M, Jordan JL, Rose S. Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomised, controlled study. Lancet. 2018 Oct 13;392(10155):1330-1339. doi: 10.1016/S0140-6736(18)32167-6. Epub 2018 Sep 21.
Results Reference
derived
Learn more about this trial
A Phase 2a, Efficacy and Safety Study of Ustekinumab in Systemic Lupus Erythematosus
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