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A Phase 2a, Efficacy and Safety Study of Ustekinumab in Systemic Lupus Erythematosus

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ClinicalTrials.gov Identifier: NCT02349061
Recruitment Status : Completed
First Posted : January 28, 2015
Results First Posted : June 12, 2018
Last Update Posted : March 24, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE January 23, 2015
First Posted Date  ICMJE January 28, 2015
Results First Submitted Date  ICMJE May 15, 2018
Results First Posted Date  ICMJE June 12, 2018
Last Update Posted Date March 24, 2020
Actual Study Start Date  ICMJE October 15, 2015
Actual Primary Completion Date May 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
Percentage of Participants With a Systemic Lupus Erythematosus Responder Index (SRI-4) Composite Response (CR) at Week 24 [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: January 23, 2015)
Percentage of Participants With a Composite SRI-4 Response at Week 24 [ Time Frame: Week 24 ]
Systemic Lupus Erythematosus Responder index (SRI-4) is defined as greater than or equal to (>=) 4 point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, no new domain scores in either British Isles Lupus Assessment Group (BILAG) A or B and no worsening (less than [˂] 10 millimeters [mm] increase) from baseline in the Physician's Global Assessment of Disease Activity (PGA). The SLEDAI - 2k assessment consists of 24 items which has total score of 0 to 105, with higher scores representing increased disease activity. The BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 8 organ systems. For each organ system, letter score was given: 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 (VAS) = from 'very well' (0) to 'very poor' (10).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2020)
  • Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) Score at Week 24 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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 [ Time Frame: 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 [ Time Frame: Baseline, 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2015)
  • Change From Baseline in SLEDAI-2K Score at Week 24 [ Time Frame: Week 24 ]
    Systemic lupus erythematosus disease activity index 2000 (SLEDAI - 2k) assessment consists of 24 items. A weighted score of 8, 4, 2, and 1 were assigned for items 1 to 8, items 9 to 14, items 15 to 21, and items 22 to 24, respectively. A SLEDAI global score for Systemic lupus erythematosus (SLE) disease activity was derived by adding all weighted scores. Total possible score range for SLEDAI - 2K global score is 0 to 105, with higher scores representing increased disease activity.
  • Change From Baseline in Physician Global Assessment of Disease Activity (PGA) at Week 24 [ Time Frame: Week 24 ]
    The Physician Global Assessment of Disease Activity will be recorded on a visual analogue scale (VAS = 0 to 10 centimeters [cm]). The scale for the assessments range from 'no lupus activity' (0) to 'extremely active lupus' (10).
  • Percentage of Participants With BICLA Response at Week 24 [ Time Frame: Week 24 ]
    The BILAG-based Combined Lupus Assessment (BICLA) requires participants to meet response criteria across 3 assessment tools and no treatment failure must be recorded: 1) BILAG improvement classified as: a) All BILAG A scores at baseline improved to either BILAG B, C or D b) All BILAG B scores at baseline improved to either BILAG C or D, c) No worsening in disease activity defined as no new BILAG A scores and <= 1 new BILAG B score. 2) No worsening of total SLEDAI-2K from baseline (change <= 0). 3) No significant deterioration (<10 mm increase) in 100 mm visual analogue PGA scale.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2a, Efficacy and Safety Study of Ustekinumab in Systemic Lupus Erythematosus
Official Title  ICMJE A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study of Ustekinumab in Subjects With Active Systemic Lupus Erythematosus
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Lupus Erythematosus, Systemic
Intervention  ICMJE
  • Drug: Ustekinumab IV
    Weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0.
    Other Name: STELARA
  • Drug: Placebo Infusion
    Placebo intravenously at Week 0.
  • Drug: Placebo SC
    Placebo subcutaneously at Weeks 8 and 16.
  • Drug: Ustekinumab SC
    Ustekinumab 90 mg subcutaneously every 8 weeks up to Week 40 and up to Week 104 in study extension (for eligible participants)
  • Other: Concomitant Medication
    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.
Study Arms  ICMJE
  • Experimental: Ustekinumab plus Concomitant Medication
    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.
    Interventions:
    • Drug: Ustekinumab IV
    • Drug: Ustekinumab SC
    • Other: Concomitant Medication
  • Experimental: Placebo followed by Ustekinumab plus Concomitant Medication
    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.
    Interventions:
    • Drug: Placebo Infusion
    • Drug: Placebo SC
    • Drug: Ustekinumab SC
    • Other: Concomitant Medication
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 5, 2017)
102
Original Estimated Enrollment  ICMJE
 (submitted: January 23, 2015)
100
Actual Study Completion Date  ICMJE March 13, 2019
Actual Primary Completion Date May 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Germany,   Hungary,   Mexico,   Poland,   Spain,   Taiwan,   United States
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02349061
Other Study ID Numbers  ICMJE CR106661
CNTO1275SLE2001 ( Other Identifier: Janssen Research & Development, LLC )
2014-005000-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP