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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02349061
First Posted: January 28, 2015
Last Update Posted: September 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
  Purpose
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).

Condition Intervention Phase
Lupus Erythematosus, Systemic Drug: Ustekinumab IV Drug: Placebo Infusion Drug: Placebo SC Drug: Ustekinumab SC Other: Concomitant Medication Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study of Ustekinumab in Subjects With Active Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • 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 a composite endpoint requiring at least a 4 point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, no worsening (less than [˂] 10 millimeters [mm] increase) from baseline in the Physician's Global Assessment of Disease Activity score (PGA) and no new British Isles Lupus Assessment Group (BILAG) Domain A and no more than 1 new BILAG Domain B scores. The SLEDAI-2k assessment consists of 24 items with 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 9 organ systems. For each organ system, a letter score is 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).


Secondary Outcome Measures:
  • 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. Weighted scores of 8, 4, 2, and 1 are assigned for items 1 to 8, items 9 to 14, items 15 to 21, and items 22 to 24, respectively. A SLEDAI global score is derived by adding all weighted scores. Total possible score range for SLEDAI - 2K 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.


Enrollment: 102
Actual Study Start Date: October 15, 2015
Estimated Study Completion Date: March 21, 2019
Primary Completion Date: May 15, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Ustekinumab IV
Weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0.
Other Name: STELARA
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.
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.
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.

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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02349061


  Show 44 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02349061     History of Changes
Other Study ID Numbers: CR106661
CNTO1275SLE2001 ( Other Identifier: Janssen Research & Development, LLC )
2014-005000-19 ( EudraCT Number )
First Submitted: January 23, 2015
First Posted: January 28, 2015
Last Update Posted: September 8, 2017
Last Verified: September 2017

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

Keywords provided by Janssen Research & Development, LLC:
Systemic Lupus Erythematosus
Ustekinumab

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Ustekinumab
Dermatologic Agents