Clinical trial NCT02349061: A Phase 2a, Efficacy and Safety Study of Ustekinumab in Systemic Lupus Erythematosus
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study of Ustekinumab in Subjects With Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Erythematosus, Systemic
Keywords: Systemic Lupus Erythematosus
Ustekinumab
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-01-28
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 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 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)

Primary outcomes:
measure: Percentage of Participants With a Systemic Lupus Erythematosus Responder Index (SRI-4) Composite Response (CR) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Score at Week 24
timeFrame: Baseline, Week 24
measure: Number of Participants With BILAG-based Combined Lupus Assessment (BICLA) Response at Week 24
timeFrame: Week 24
measure: Change From Baseline in Number of Joints With Pain and Signs of Inflammation at Week 24
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Beverly Hills
country: United States
state: California
city: Tampa
country: United States
state: Florida
city: Lansing
country: United States
state: Michigan
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Tulsa
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Jackson
country: United States
state: Tennessee
city: Buenos Aires
country: Argentina
city: Ciudad De San Miguel De Tucuman
country: Argentina
city: San Juan
country: Argentina
city: Adelaide
country: Australia
city: Camberwell
country: Australia
city: Heidelberg
country: Australia
city: Liverpool
country: Australia
city: Nedlands
country: Australia
city: Berlin
country: Germany
city: Frankfurt
country: Germany
city: Koeln
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Szeged
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Chihuahua
country: Mexico
city: Guadalajara
country: Mexico
city: Leon
country: Mexico
city: Mexico
country: Mexico
city: Bydgoszcz
country: Poland
city: Poznan
country: Poland
city: Szczecin
country: Poland
city: Wroclaw
country: Poland
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Santiago de Compostela
country: Spain
city: Sevilla
country: Spain
city: Kaohsiung
country: Taiwan
city: Taichung City
country: Taiwan
city: Taichung
country: Taiwan
city: Taoyuan
country: Taiwan
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: van Vollenhoven RF, Hahn BH, Tsokos GC, Lipsky P, Gordon RM, Fei K, Lo KH, Chevrier M, Rose S, Berry P, Yao Z, Karyekar CS, Zuraw Q. Efficacy and Safety of Ustekinumab in Patients With Active Systemic Lupus Erythematosus: Results of a Phase II Open-label Extension Study. J Rheumatol. 2022 Apr;49(4):380-387. doi: 10.3899/jrheum.210805. Epub 2021 Dec 1.
citation: 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.
citation: Cesaroni M, Seridi L, Loza MJ, Schreiter J, Sweet K, Franks C, Ma K, Orillion A, Campbell K, M Gordon R, Branigan P, Lipsky P, van Vollenhoven R, Hahn BH, Tsokos GC, Chevrier M, Rose S, Baribaud F, Jordan J. Suppression of Serum Interferon-gamma Levels as a Potential Measure of Response to Ustekinumab Treatment in Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2021 Mar;73(3):472-477. doi: 10.1002/art.41547. Epub 2021 Feb 1.
citation: van Vollenhoven RF, Hahn BH, Tsokos GC, Lipsky P, Fei K, Gordon RM, Gregan I, Lo KH, Chevrier M, Rose S. Maintenance of Efficacy and Safety of Ustekinumab Through One Year in a Phase II Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Patients With Active Systemic Lupus Erythematosus. Arthritis Rheumatol. 2020 May;72(5):761-768. doi: 10.1002/art.41179. Epub 2020 Apr 1.
citation: 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.