A Study of Ustekinumab in Chinese Participants With Active Systemic Lupus Erythematosus

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Chinese Subjects With Active Systemic Lupus Erythematosus

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

Study Overview

• Status: Withdrawn
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Drug: Placebo; Drug: Ustekinumab (approximately 6 mg/kg); Drug: Ustekinumab 90 milligram (mg)

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510080
    • Guangdong Provincial People's Hospital
  • Hefei, China, 230001
    • Anhui Province Hospital
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Had 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)
• Have 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
• Have at least 1 British Isles Lupus Assessment Group (BILAG) A and/or 2 BILAG B scores observed during screening
• Have a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score at least 4 (excluding diffuse non-inflammatory alopecia) or at least 4 joints with pain and signs of inflammation at screening, Week 0, or both
• Have a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score greater than or equal to [>=] 6 at screening. Must also have SLEDAI-2K >= 4 for clinical features (excluding headache and laboratory abnormalities) at Week 0

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 inflammatory diseases that might confound the evaluations of efficacy (including but not limited to rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease)
• Has urinary protein level of greater than (>) 4 gram per day (g/day) or protein/creatinine ratio estimating >4g/day equivalent proteinuria
• Has known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients
• Has a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location, clinically significant splenomegaly, or history of monoclonal gammopathy of undetermined significance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 milligram per kilogram via IV route based on body weight-range.; Other Names: Stelara; Drug: Ustekinumab 90 milligram (mg); Participants will receive 90 mg ustekinumab via SC route.; Other Names: Stelara
Placebo Comparator: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Composite Response at Week 52	SRI-4 is a composite of at least 4 point improvement in Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K), no worsening in British Isles Lupus Assessment Group (BILAG) and no worsening in Physician's Global Assessment of Disease Activity score (PGA).	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Flare	Time to flare is the duration of flare occurring at any time after the baseline will be calculated with flare defined as either 1 or more new British Isles Lupus Assessment Group (BILAG) A or 2 or more new BILAG B domain scores relative to baseline.	Baseline up to Week 52
Percentage of Participants with an SRI-4 Composite Response at Week 24	SLE Responder Index (SRI)-4 is a composite of at least 4 point improvement in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, no worsening in BILAG and no worsening in PGA.	Week 24
Percentage of Participants Achieving at Least a 50% Improvement in the Number of Joints with Pain and Signs of Inflammation at Week 52	The percentage of participants achieving at least a 50 percent (%) improvement in the number of joints with pain and signs of inflammation at week 52 will be reported in participants with at least 4 affected joints at baseline.	Week 52
Percentage of Participants Receiving Glucocorticoids at Baseline who Achieve Reduction in Glucocorticoid Dose by Week 40 and Sustain That Reduction Through Week 52	Reduction of glucocorticoid dose is 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 is reduced to less than or equal to (<=) 7.5 milligram (mg) (prednisone or equivalent). Sustained reduction of glucocorticoid dose is 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.	Baseline up to Week 52
Percentage of Participants Achieving at Least a 50% Improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 52	Percentage of participants achieving at least 50% improvement in CLASI Activity Score at Week 52 will be reported in participants with a CLASI Activity Score of 4 or greater at baseline.	Week 52
Percentage of Participants Receiving Glucocorticoids at Baseline who Achieve Reduction in Glucocorticoid Dose by Week 40, Sustain That Reduction Through Week 52, and Achieve an SRI-4 Composite Response at Week 52	Percentage of participants receiving glucocorticoids at baseline who achieve reduction in glucocorticoid dose by Week 40, sustain that reduction through Week 52, and achieve an SRI-4 composite response at Week 52 will be reported.	Baseline up to Week 52

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 14, 2020
• Primary Completion (Anticipated): January 31, 2022
• Study Completion (Anticipated): March 31, 2026

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: August 16, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: CR108631; CNTO1275SLE3003 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No