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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: 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 Summary: 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.
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome: 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).


Original Primary Outcome: 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).


Current Secondary Outcome:

  • 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.


Original Secondary Outcome:

  • 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.


Information By: Janssen Research & Development, LLC

Dates:
Date Received: January 23, 2015
Date Started: October 15, 2015
Date Completion: March 21, 2019
Last Updated: May 16, 2017
Last Verified: May 2017