A Study of Ustekinumab in Participants With Active Systemic Lupus Erythematosus

Janssen (J&J Innovative Medicine)

Status and phase: Terminated; Phase 3

Conditions: Lupus Erythematosus, Systemic

Treatments: Drug: Ustekinumab (approximately 6 mg/kg); Drug: Ustekinumab 90 mg; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03517722

CNTO1275SLE3001 (Other Identifier)

2017-001489-53 (EudraCT Number)

CR108440

Details and patient eligibility

About

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

Full description

This study evaluates the efficacy, safety, and tolerability of ustekinumab in participants with active SLE according to Systemic Lupus International Collaborating Clinics (SLICC) criteria Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score greater than (>=) 6, despite receiving one or more standard-of-care treatments (example, immunomodulators, antimalarial drugs, and/or glucocorticoids). The total duration of the study is up to 182 weeks, consisting of 3 study periods: a screening period (approximately 6 weeks), a double blind period (52 weeks), and an extension period (124 weeks). Other study evaluations will include pharmacokinetics, immunogenicity, biomarkers and pharmacogenomic evaluations. The safety of the participants enrolled in the study will be monitored on an ongoing basis throughout the study.

Enrollment: 516 patients

Sex: All

Ages: 16 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Be male or female

• Has 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)

• Has 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

• Has greater than or equal to (>=) 1 British Isles Lupus Assessment Group (BILAG) A and/or >= 2 BILAG B scores observed during screening

• Has a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score >=4 (excluding diffuse non-inflammatory alopecia) or >= 4 joints with pain and signs of inflammation at screening, Week 0, or both

• Has a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score >=6 at screening. Must also have SLEDAI-2K >= 4 for clinical features (excluding headache and laboratory abnormalities) at Week 0

• Cannot be pregnant, nursing, intending to become pregnant, or unwilling to follow contraception or egg/sperm donation guidelines

• Must be receiving stable doses of >=1 protocol-permitted standard of care SLE treatment: oral glucocorticoids, anti-malarials, immunomodulators (methotrexate, azathioprine, 6-mercaptopurine, mycophenolate mofetil, mycophenolic acid)

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 co-existent inflammatory diseases (example: rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease)
• Has a urinary protein to creatinine ratio of greater than (>)4 gram per gram (g/g) per day
• Has an acute or chronic infectious illness (example: human immunodeficiency virus, hepatitis B or C virus, tuberculosis, opportunistic infections)
• Has a history of cancer or lymphoproliferative disease within the last 5 years except for treated and non-recurrent cutaneous basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma
• Has any condition requiring multiple courses of systemic glucocorticoids (example: uncontrolled asthma, chronic obstructive pulmonary disease)
• Has a history of major surgery within the last month
• Has received live virus or bacterial vaccines within 16 weeks prior to first dose of study agent or Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening
• Has previously received ustekinumab
• Has received cyclophosphamide orally within 90 days or intravenously within 180 days of screening
• Has received a single B-cell targeted therapy (e.g. belimumab) within 3 months, >1 previous B-cell targeted therapy within 6 months, or B-cell depleting therapy (example: rituximab) within 12 months of first dose of study agent
• Has received protocol-prohibited oral or biologic immunomodulatory therapy in the last 3 months or less than (<)5 half-lives (whichever is longer) prior to first dose of study agent
• Has received adrenocorticotropic hormone (ACTH) within 1 month prior to first dose of study agent
• Has received epidural, intravenous, intramuscular, intraarticular, intrabursal, intralesional glucocorticoids within 6 weeks of first dose of study agent
• Locally-delivered therapies except for ophthalmic use of cyclosporine A or topical use of nonsteroidal anti inflammatory drugs (NSAIDs), analgesics, or high-potency glucocorticoids (World Health Organization criteria) are prohibited

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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516 participants in 2 patient groups

Ustekinumab

Experimental group

Description:

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.

Treatment:

Drug: Ustekinumab 90 mg

Drug: Ustekinumab (approximately 6 mg/kg)

Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Ustekinumab 90 mg