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 : April 11, 2019

Sponsor:

Information provided by (Responsible Party):

Janssen Research & Development, LLC

Study Description

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).

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

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	102 participants
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
Actual Study Start Date :	October 15, 2015
Actual Primary Completion Date :	May 15, 2017
Actual Study Completion Date :	March 13, 2019

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Systemic lupus erythematosus

MedlinePlus related topics: Lupus

Drug Information available for: Ustekinumab

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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.

Arm

Intervention/treatment

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

Outcome Measures

Primary Outcome Measures :

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).

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
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

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Study Director:	Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC

Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:

Study Protocol [PDF] January 18, 2017

Statistical Analysis Plan [PDF] March 22, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

van Vollenhoven RF, Hahn BH, Tsokos GC, Wagner CL, Lipsky P, Touma Z, Werth VP, Gordon RM, Zhou B, Hsu B, Chevrier M, Triebel M, Jordan JL, Rose S. Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomised, controlled study. Lancet. 2018 Oct 13;392(10155):1330-1339. doi: 10.1016/S0140-6736(18)32167-6. Epub 2018 Sep 21.

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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 Posted:	January 28, 2015 Key Record Dates
Results First Posted:	June 12, 2018
Last Update Posted:	April 11, 2019
Last Verified:	March 2019

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

Keywords provided by Janssen Research & Development, LLC:


Systemic Lupus Erythematosus Ustekinumab

Additional relevant MeSH terms:

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Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases	Immune System Diseases Ustekinumab Dermatologic Agents

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