A Study to Evaluate the Efficacy and Safety of CEP-33457 in Participants With Systemic Lupus Erythematosus (SLE)

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a 200-mcg Dose of CEP-33457 in Patients With Systemic Lupus Erythematosus

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.

The study consisted of a 2-week screening period (visit 1), a 20-week treatment period beginning with a baseline visit in which randomization was completed and study drug treatment began (visits 2 through 7), and a final assessment was performed 4 weeks after the last dose of study drug (visit 8 [week 24 or early termination]). Participants were randomized to receive either CEP-33457 or placebo subcutaneously (SC) every 4 weeks. Plasma samples for measurement of study drug concentration were collected in a subset of participants and study drug was administered at each study visit until the final visit. The dose of background steroid medication may have been increased, if needed, to treat the participant for minor fluctuations in lupus disease activity. One interim analysis was conducted when at least 80 participants completed Week 12 or had been withdrawn from the study. Participants who completed the treatment period returned to the study center 4 weeks after the last dose had been administered for final procedures and assessments. Final procedures and assessments for participants who withdrew from the study before 20 weeks of treatment were performed at the last visit. Final procedures and assessments for participants who participated in the study beyond week 24 were to be performed at the next regularly scheduled visit. Participants who complete the study will be eligible for participation in the 12-month open-label study (study C33457/3075; herein referred to as study 3075) to assess continued effectiveness and safety of the CEP-33457 treatment.

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.