Clinical trial NCT01135459 (phase 2, status: completed)
Conditions: systemic lupus erythematosus
ICD codes: M32.9, M32.0, M32.11, M32.12, M32.13, M32.14, M32.8
Drugs: lupuzor, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  The patient 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 patient 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 patient has a clinical SLEDAI-2K score of at least 6 points during screening.

          -  The patient 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 patient 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 patient 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 patient has been treated with intramuscular or intravenous (iv) pulse steroids
             (ie, 250 to 1000 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 patient has received tacrolimus, cyclosporine A, or iv immunoglobulins (IVIG)
             within 3 months of the first dose of study drug.

          -  The patient has received cyclophosphamide within 12 months prior to the first dose of
             study drug.

          -  The patient 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 patient 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 patient has New York Heart Association (NYHA) Class III or IV congestive heart
             failure.

          -  The patient has severe active lupus nephritis or cerebritis.

          -  The patient has an estimated glomerular filtration rate (eGFR) of less than 30
             mL/min/1.73 m2 (via Modification of Diet in Renal Disease [MDRD] equation).

          -  The patient 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 patient 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 patient has any clinically significant abnormalities on ECG that are not related
             to SLE, as determined by the investigator. Patients with stable ECG changes without
             evidence of active cardiovascular disease may participate at the discretion of the
             investigator and medical monitor.

          -  The patient 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 patient 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 patient 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 patient has a positive test result for hepatitis B surface antigen (HBsAg) or
             antibodies to hepatitis C (HCV Ab).

          -  The patient has a known positive history of antibodies to human immunodeficiency virus
             (HIV) or HIV disease.

          -  The patient 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 patient has a history of severe allergic reactions to or hypersensitivity to any
             component of the study drug or placebo.

          -  The patient 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 patient has previously participated in a Cephalon- or ImmuPharma-sponsored
             clinical study with CEP-33457.

          -  The patient is a pregnant or lactating woman. (Any women becoming pregnant during the
             study will be withdrawn from the study.)

          -  The patient is unlikely to comply with the study protocol or is unsuitable for any
             other reason, as judged by the investigator or medical monitor.