Study of Ustekinumab in Subjects with Active Systemic Lupus Erythematosus
- Conditions
- Systemic Lupus ErythematosusMedDRA version: 20.0Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2017-001489-53-BG
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 516
• Between 16 (unless restricted by local requirements) and 75 years of age, inclusive.
• Diagnosis of SLE made or confirmed by a physician experienced in the treatment of SLE.
• Documented medical history (ie, met at least 1 of the bulleted criteria below) that subject met the SLICC classification criteria for SLE at least 3 months prior to first dose of study agent:
- Met a total of at least 4 SLICC criteria including at least 1 clinical and at least 1 immunologic.
- Had a diagnosis of lupus nephritis, confirmed by renal biopsy and at least 1 of the following autoantibodies: ANA or anti-dsDNA.
• At least 1 well-documented unequivocally positive test in medical history and detected during screening, for at least 1 of the following autoantibodies: ANA, anti-dsDNA, and/or anti-Smith.
• Have at least 1 BILAG A and/or 2 BILAG B domain scores observed during screening.
• Have a CLASI activity score of at least 4 or at least 4 joints with pain and signs of inflammation at screening or at Week 0, or both.
• Demonstrate active disease based on SLEDAI-2K score =6 observed during screening. Must also have SLEDAI-2K =4 for clinical features (ie, SLEDAI-2K score excluding headache, and laboratory abnormalities) present at Week 0 prior to randomization.
• Must be receiving one or more of the following protocol-permitted, systemic standard-of-care treatments:
a) Oral glucocorticoids (average daily dose =20 mg of prednisone or equivalent) for =6 weeks and at a stable dose =4 weeks prior to first dose of study agent.
- If currently not using oral glucocorticoids, must not have received them for =6 weeks prior to the first dose of study agent.
b) Antimalarials for =12 weeks and at a stable dose for =6 weeks prior to first dose of study agent
c) If using one or more of the following immunomodulatory drugs, must be receiving for =12 weeks and be on a stable dose for =6 weeks prior to first dose of study agent:
-MMF =2 g/day
-MPA =1.5 g/day
-AZA /6-MP =2 mg/kg/day; up to 100 mg/day for subjects weighing =50 kg
-Oral MTX =25 mg/Week or SC or intramuscular (IM) MTX =20 mg/Week with concomitant folic acid or folinic acid.
If the subject is using concomitantly 2 or more of the immunomodulatory drugs listed above (MMF, MPA, AZA, 6-MP, MTX), the suitability of the subject to participate in the study must be discussed with the medical monitor and/or sponsor before the subject is randomized.
• Before randomization, a woman must be either:
a. Not of childbearing potential, or
b. Of childbearing potential:
-Practicing a highly effective method of contraception
-Agrees to remain on a highly effective method of contraception throughout the study and for at least 16 weeks after the last dose of study agent.
• A woman of childbearing potential must have a negative urine pregnancy tests
• beta-hCG obtained during screening and at Week 0 before the first dose of study agent.
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 4 months after receiving the last dose of study agent.
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
• A man who is sexually active with a woman who is pregnant must use a condom and all men must not donate sperm during the study and for 20 weeks after receiving the last dose of study agent.
• Subjects must have laboratory test results within the following parameters at
scree
• Has any unstable or progressive manifestation of SLE that is likely to warrant escalation in therapy beyond permitted background medications. Subjects requiring renal hemodialysis or peritoneal dialysis are also excluded.
• Has other inflammatory disease that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), PsA, RA/lupus overlap, psoriasis, Crohn’s disease, or active Lyme disease
• Is pregnant, nursing, or planning a pregnancy or planning to father a child while enrolled in the study or within 4 months after receiving the last administration of study agent
• Has received systemic immunomodulatory agents other than those described in inclusion criteria within 3 months prior to the first dose of study agent
• Has used oral cyclophosphamide within 90 days or IV cyclophosphamide within 180 days of starting screening
• Exclusions for treatment with B-cell targeted therapies*:
a. Treatment with a single B-cell targeted therapy within 3 months prior to first dose of study agent.
b. Treatment with >1 previous B-cell targeted therapy within 6 months prior to first dose of study agent.
c. Treatment with B-cell depleting therapy within 12 months prior to first dose of study agent, or have evidence of continued B-cell depletion following such therapy
*If a subject has received one or more B-cell targeted therapies, the length of time
required before administering the first dose of study agent should be whichever is the
longest applicable washout period.
• Has ever received ustekinumab
• Has received prior immunomodulatory biologic therapy not described in Section 8.1.7 of protocol less than 5 half-lives or 3 months, whichever is longer, prior to first dose of the study agent.
• Has received ACTH administered by injection within 1 month prior to the first administration of study agent
• Has received topical cream/ointment preparations of cyclosporine A, high-potency topical glucocorticoids, or other topical immunomodulatory agents within 4 weeks prior to the first administration of study agent
• Is currently receiving venom immunotherapy
• Subjects likely to require multiple courses of systemic steroids for reasons other than SLE
• Has received epidural, IV, IM, intra-articular (IA), intrabursal, or intralesional admin of glucocorticoids within 6 weeks prior to the first administration
• BCG vaccination within 12 months of screening
• Live virus or live bacterial vaccination within 16 weeks prior to the first administration of study agent
• History of active granulomatous infection, including histoplasmosis, or coccidioidomycosis
• Chest radiograph within 3 months prior to the first dose that shows an abnormality suggestive of a malignancy or current active infection, including TB
• A nontuberculous mycobacterial infection or opportunistic infection
• A history of, or ongoing, chronic or recurrent infectious disease
• History of HIV antibody positive, or tests positive for HIV at screening
• Hepatitis B infection. Subjects must undergo screening for hepatitis B virus
• Seropositive for antibodies to hepatitis C virus (HCV), unless has 2 negative HCV RNA test results 6 months apart prior to screening and has a third negative HCV RNA test result at screening
• Has experienced a recent single dermatomal herpes zoster eruption within the past 4 months. Has ever had multi-dermatomal herpes zoster or CNS zoster infection
• Within 2 months prior to first administration of study agent, has had a seriou
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method