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

NCT ID: NCT02349061

Last Updated: 2020-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-15
• Study Completion Date: 2019-03-13

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.

Conditions

Lupus Erythematosus, Systemic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Ustekinumab IV

Intervention Type: DRUG

Weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0.

Ustekinumab SC

Intervention Type: DRUG

Ustekinumab 90 mg subcutaneously every 8 weeks up to Week 40 and up to Week 104 in study extension (for eligible participants)

Concomitant Medication

Intervention Type: OTHER

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.

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.

Group Type: EXPERIMENTAL

Placebo Infusion

Intervention Type: DRUG

Placebo intravenously at Week 0.

Placebo SC

Intervention Type: DRUG

Placebo subcutaneously at Weeks 8 and 16.

Ustekinumab SC

Intervention Type: DRUG

Ustekinumab 90 mg subcutaneously every 8 weeks up to Week 40 and up to Week 104 in study extension (for eligible participants)

Concomitant Medication

Intervention Type: OTHER

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.

Interventions

Ustekinumab IV

Weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0.

Intervention Type: DRUG

Placebo Infusion

Placebo intravenously at Week 0.

Intervention Type: DRUG

Placebo SC

Placebo subcutaneously at Weeks 8 and 16.

Intervention Type: 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)

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

STELARA

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

• 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)

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Huntsville, Alabama, United States

Beverly Hills, California, United States

Tampa, Florida, United States

Lansing, Michigan, United States

Manhasset, New York, United States

New York, New York, United States

Syracuse, New York, United States

Tulsa, Oklahoma, United States

Duncansville, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Charleston, South Carolina, United States

Jackson, Tennessee, United States

Buenos Aires, , Argentina

Ciudad de San Miguel de Tucuman, , Argentina

San Juan, , Argentina

Adelaide, , Australia

Camberwell, , Australia

Heidelberg, , Australia

Liverpool, , Australia

Nedlands, , Australia

Berlin, , Germany

Cologne, , Germany

Frankfurt, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Szeged, , Hungary

Zalaegerszeg, , Hungary

Chihuahua City, , Mexico

Guadalajara, , Mexico

León, , Mexico

México, , Mexico

Bydgoszcz, , Poland

Poznan, , Poland

Szczecin, , Poland

Wroclaw, , Poland

Barcelona, , Spain

Madrid, , Spain

Málaga, , Spain

Santiago de Compostela, , Spain

Seville, , Spain

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Taoyuan District, , Taiwan

Countries

United States; Argentina; Australia; Germany; Hungary; Mexico; Poland; Spain; Taiwan

References

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.

Reference Type: DERIVED

PMID: 34853089 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33687069 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33010188 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31769212 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30249507 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CNTO1275SLE2001

Identifier Type: OTHER

Identifier Source: secondary_id

2014-005000-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR106661

Identifier Type: -

Identifier Source: org_study_id