A Study to Evaluate the Efficacy and Safety of CEP-33457 in Participants With Systemic Lupus Erythematosus (SLE)
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: CEP-33457; Placebo
Intervention description: CEP-33457 will be administered per dose and schedule specified in the arm description.; Placebo matching to CEP-33457 will be administered per schedule specified in the arm description.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 183.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Lupus

Summary:

      The primary objective of this study is to evaluate the efficacy of a 200 micrograms (mcg)
      dose of CEP-33457 compared with placebo in participants with active systemic lupus
      erythematosus (SLE) as assessed by the proportion of participants achieving a combined
      clinical response using the SLE responder index (SRI) at Week 24.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant has an established diagnosis of systemic lupus erythematosus (SLE) as
             defined by ACR Classification Revised Criteria. The diagnosis is fulfilled provided
             that at least 4 criteria are met.

          -  The participant has a positive test for antinuclear antibody (ANA) at screening and/or
             a positive test for anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA
             Ab) at screening.

          -  Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing
             potential, using a medically accepted method of contraception, and must agree to
             continued use of this method for the duration of the study and for 30 days after
             discontinuation of study drug treatment.

          -  The participant has a clinical SLEDAI-2K score of at least 6 points during screening.

          -  The participant does not have an "A" score on the BILAG-2004 scale.

          -  If the patient is using oral corticosteroids, the weekly cumulative dose must not
             exceed 80 mg of prednisone equivalent; the weekly dose must be stable over the 4 weeks
             preceding the first dose of study drug.

          -  If the participant is using antimalarials, methotrexate, leflunomide, mycophenolate
             mofetil, or azathioprine, the start date must be at least 3 months prior to the first
             dose of study drug, and the daily dose must be stable over the 4 weeks preceding the
             first dose of study drug.

          -  If the participant is not currently using corticosteroids, antimalarials,
             methotrexate, mycophenolate mofetil, or azathioprine, the last dose (in case of
             previous use) must be at least 4 weeks prior to the first dose of study drug. For
             leflunomide, the stop date must be at least 8 weeks before the first dose of study
             drug, unless an adequate cholestyramine washout has been completed.

        Exclusion Criteria:

          -  The participant has been treated with intramuscular or intravenous (iv) pulse steroids
             (ie, 250 to 1000 milligrams [mg] iv total daily dose of methylprednisolone) within 4
             weeks of the first dose of study drug. The use of intra-articular steroids may be
             allowed after consultation with the medical expert.

          -  The participant has received tacrolimus, cyclosporine A, or iv immunoglobulins (IVIG)
             within 3 months of the first dose of study drug.

          -  The participant has received cyclophosphamide within 12 months prior to the first dose
             of study drug.

          -  The participant has been treated for SLE with agents such as fusion proteins,
             therapeutic proteins, or monoclonal antibodies or antibody fragments, within 12 months
             of the first dose of study drug.

          -  The participant has received B-cell depleting agents such as rituximab and has not yet
             normalized the B-cell count (ie, CD20+ B-cell count is less than 200 and the absolute
             lymphocyte count [ALC] is less than 1500/μL).

          -  The participant has New York Heart Association (NYHA) Class III or IV congestive heart
             failure.

          -  The participant has severe active lupus nephritis or cerebritis.

          -  The participant has an estimated glomerular filtration rate (eGFR) of less than 30
             milliliters (mL)/minute (min)/1.73 square meter (m^2) (via Modification of Diet in
             Renal Disease [MDRD] equation).

          -  The participant has an aspartate aminotransferase (AST) or alanine aminotransferase
             (ALT) value greater than 2 times the upper limit of normal (ULN) or a total bilirubin
             level greater than 1.5 times ULN.

          -  The participant has a planned immunization with a live or live attenuated vaccine
             within 3 months prior to administration of the first dose of study drug and for 3
             months after administration of the last dose of study drug.

          -  The participant has any clinically significant abnormalities on electrocardiogram
             (ECG) that are not related to SLE, as determined by the investigator. Participant with
             stable ECG changes without evidence of active cardiovascular disease may participate
             at the discretion of the investigator and medical monitor.

          -  The participant has an ongoing active systemic infection requiring treatment or a
             history of severe infection, such as hepatitis or pneumonia, in the 3 months prior to
             administration of the first dose of study drug. Less severe infections in the 3 months
             prior to administration of the first dose of study drug are permitted at the
             discretion of the investigator and medical monitor.

          -  The participant has any concomitant medical condition unrelated to SLE that may
             interfere with his or her safety or with evaluation of the study drug, as determined
             by the investigator.

          -  The participant has a history of a medical condition other than SLE that has required
             treatment with steroids in excess of 80 mg of prednisone equivalent/week within 6
             months of the first dose of study drug.

          -  The participant has a positive test result for hepatitis B surface antigen (HBsAg) or
             antibodies to hepatitis C (HCV Ab).

          -  The participant has a known positive history of antibodies to human immunodeficiency
             virus (HIV) or HIV disease.

          -  The participant has a history of alcohol or substance dependence or abuse (with the
             exception of nicotine), according to the Diagnostic and Statistical Manual of Mental
             Disorders of the American Psychiatric Association, Fourth Edition, Text Revision
             (DSM-IV-TR), within 3 months of the screening visit or has current substance abuse.

          -  The participant has a history of severe allergic reactions to or hypersensitivity to
             any component of the study drug or placebo.

          -  The participant has undergone or is undergoing treatment with another investigational
             drug for the treatment of lupus within 6 months prior to the 1st dose of study drug or
             has received any other investigational drug for any other condition within 30 days
             prior to the 1st dose of study drug.

          -  The participant has previously participated in a Cephalon- or ImmuPharma-sponsored
             clinical study with CEP-33457.

          -  The participant is a pregnant or lactating woman. (Any women becoming pregnant during
             the study will be withdrawn from the study.)

          -  The participant is unlikely to comply with the study protocol or is unsuitable for any
             other reason, as judged by the investigator or medical monitor.