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

NCT02349061 | Completed Phase 2 Results DMC

• 3 other identifiers: CR106661CNTO1275SLE20012014-005000-19
• Study Type: interventional
• Target: 102
• Locations: 9 countries
• Sites: 43

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).

Conditions

Lupus Erythematosus, Systemic

Keywords

Systemic Lupus Erythematosus; Ustekinumab

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Systemic Lupus Erythematosus Responder Index (SRI-4) Composite Response (CR) at 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).

  Week 24

Secondary Outcomes (4)

• Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) Score at Week 24

  Baseline, Week 24

• Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Score at Week 24

  Baseline, Week 24

• Number of Participants With BILAG-based Combined Lupus Assessment (BICLA) Response at Week 24

  Week 24

• Change From Baseline in Number of Joints With Pain and Signs of Inflammation at Week 24

  Baseline, Week 24

Study Arms (2)

Ustekinumab plus Concomitant Medication

EXPERIMENTAL

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; Drug: Ustekinumab SC; Other: Concomitant Medication

Placebo followed by Ustekinumab plus Concomitant Medication

EXPERIMENTAL

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; Drug: Placebo SC; Drug: Ustekinumab SC; Other: Concomitant Medication

Interventions

Ustekinumab IV DRUG

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

Also known as: STELARA

Ustekinumab plus Concomitant Medication

Placebo Infusion DRUG

Placebo intravenously at Week 0.

Placebo followed by Ustekinumab plus Concomitant Medication

Placebo SC DRUG

Placebo subcutaneously at Weeks 8 and 16.

Placebo followed by Ustekinumab plus Concomitant Medication

Ustekinumab SC DRUG

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

Placebo followed by Ustekinumab plus Concomitant Medication; Ustekinumab plus Concomitant Medication

Concomitant Medication 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; Ustekinumab plus Concomitant Medication

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (43)

Unknown Facility

Huntsville, Alabama, United States

Location

Unknown Facility

Beverly Hills, California, United States

Location

Unknown Facility

Tampa, Florida, United States

Location

Unknown Facility

Lansing, Michigan, United States

Location

Unknown Facility

Manhasset, New York, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Syracuse, New York, United States

Location

Unknown Facility

Tulsa, Oklahoma, United States

Location

Unknown Facility

Duncansville, Pennsylvania, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Charleston, South Carolina, United States

Location

Unknown Facility

Jackson, Tennessee, United States

Location

Unknown Facility

Buenos Aires, Argentina

Location

Unknown Facility

Ciudad de San Miguel de Tucuman, Argentina

Location

Unknown Facility

San Juan, Argentina

Location

Unknown Facility

Adelaide, Australia

Location

Unknown Facility

Camberwell, Australia

Location

Unknown Facility

Heidelberg, Australia

Location

Unknown Facility

Liverpool, Australia

Location

Unknown Facility

Nedlands, Australia

Location

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Cologne, Germany

Location

Unknown Facility

Frankfurt, Germany

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Debrecen, Hungary

Location

Unknown Facility

Szeged, Hungary

Location

Unknown Facility

Zalaegerszeg, Hungary

Location

Unknown Facility

Chihuahua City, Mexico

Location

Unknown Facility

Guadalajara, Mexico

Location

Unknown Facility

León, Mexico

Location

Unknown Facility

México, Mexico

Location

Unknown Facility

Bydgoszcz, Poland

Location

Unknown Facility

Poznan, Poland

Location

Unknown Facility

Szczecin, Poland

Location

Unknown Facility

Wroclaw, Poland

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Málaga, Spain

Location

Unknown Facility

Santiago de Compostela, Spain

Location

Unknown Facility

Seville, Spain

Location

Unknown Facility

Kaohsiung City, Taiwan

Location

Unknown Facility

Taichung, Taiwan

Location

Unknown Facility

Taoyuan District, Taiwan

Location

Related Publications (5)

• 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.

  PMID: 34853089 DERIVED

• 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.

  PMID: 33687069 DERIVED

• 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.

  PMID: 33010188 DERIVED

• 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.

  PMID: 31769212 DERIVED

• 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.

  PMID: 30249507 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Senior Director Clinical Development
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: January 28, 2015
• Study Start: October 15, 2015
• Primary Completion: May 15, 2017
• Study Completion: March 13, 2019
• Last Updated: March 24, 2020
• Results First Posted: June 12, 2018

Record last verified: 2020-03

Locations

PL (4); HU (4); ES (5); US (12); AR (3); ME (4); DE (3); TW (3); AU (5)