Clinical trial NCT00657189 (phase 2, status: completed)
Conditions: lupus erythematosus, systemic, lupus
ICD codes: M32.9, M32.0, M32.11, M32.12, M32.13, M32.14, M32.8, D68.62, L93.0, L93.1, L93.2, M32.9, M32.0, M32.11
Drugs: medi-545, medi-545, medi-545, medi-545, 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:

          -  Male or female subjects ≥ 18 years at the time of the first dose of study drug;

          -  Written informed consent and HIPAA authorization (applies to covered entities in the
             US only) obtained from the subject or subject's legal representative;

          -  Meet at least 4 of the 11 revised ACR classification criteria for SLE

          -  Have positive antinuclear antibody test (ANA) at ≥ 1:80 serum dilution documented in
             the past or at screening;

          -  Have at least 1 system with a score of A or 2 systems with a score of B on the BILAG
             index at screening, or have a SELENA-SLEDAI score ≥ 6;

          -  Treatment for SLE with antimalarials, oral prednisone or another systemic
             corticosteroid, mycophenolate mofetil, methotrexate, leflunomide, azathioprine, or
             dapsone;

          -  Women, unless surgically sterile or at least 2 years post-menopausal, must use an
             effective method of avoiding pregnancy (including oral, injectable, transdermal, or
             implanted contraceptives, intrauterine device, diaphragm with spermicide, cervical
             cap, abstinence, or sterile sexual partner) in addition to the use of condoms (male or
             female condoms with spermicide) from screening through the end of the study. Cessation
             of birth control after this point should be discussed with a responsible physician.
             Men unless surgically sterile, must likewise practice 2 effective methods of birth
             control (condom with spermicide or abstinence) from Study Day 0 through the end of the
             study;

          -  Ability to complete the study period, including the follow-up period through Study Day
             168; and

          -  Willing to forego other forms of experimental treatment during the study.

        Exclusion Criteria:

          -  Have received MEDI-545 within 120 days prior to screening;

          -  History of allergy or reaction to any component of the study drug formulation;

          -  Have received the following medications within 28 days before randomization:

               -  Systemic cyclophosphamide at any dose

               -  Cyclosporine at any dose

               -  Thalidomide at any dose

               -  Hydroxychloroquine > 600 mg/day

               -  Mycophenolate mofetil > 3 g/day

               -  Methotrexate > 25 mg/week

               -  Azathioprine > 3 mg/kg/day

          -  Have received fluctuating doses of the following within 28 days before randomization:

               -  Antimalarials

               -  Mycophenolate mofetil

               -  Methotrexate

               -  Leflunomide

               -  Azathioprine

               -  Dapsone

          -  Have received Leflunomide > 20mg/day in the 6 months prior to Study Day 0;

          -  Have received prednisone > 20 mg/day or in fluctuating doses within 14 days before
             randomization;

          -  Have received fluctuating doses of non-steroidal anti-inflammatory drugs within 14
             days before randomization;

          -  Treatment with any investigational drug therapy within 28 days before randomization
             into the study, B cell-depleting therapies within 12 months before randomization, or
             biologic therapies within 30 days or 5 half-lives of the biologic agent, whichever is
             longer, before randomization into the study;

          -  In the investigator's opinion, evidence of clinically significant active infection,
             including ongoing, chronic infection, within 28 days before randomization;

          -  A history of severe viral infection as judged by the investigators, including severe
             infections of either cytomegalovirus or the herpes family such as disseminated herpes,
             herpes encephalitis, ophthalmic herpes;

          -  Herpes zoster infection within 3 months before randomization;

          -  Evidence of infection with hepatitis B or C virus, or human immunodeficiency virus
             (HIV)-1 or HIV-2, or active infection with hepatitis A, as determined by results of
             testing at screening

          -  Vaccination with live attenuated viruses within 28 days before randomization;

          -  Pregnancy (women, unless surgically sterile or at least 2 years post-menopausal, must
             have a negative serum pregnancy test within 28 days before receiving the study drug
             and a negative urine pregnancy test on days of study drug administration before
             receiving the study drug);

          -  Breastfeeding or lactating women;

          -  History of primary immunodeficiency;

          -  History of alcohol or drug abuse < 1 year prior to randomization;

          -  History of cancer (except basal cell carcinoma or in situ carcinoma of the cervix
             treated with apparent success with curative therapy > 1 year prior to randomization);

          -  History of active tuberculosis (TB) infection or newly positive TB skin test (defined
             as a reaction ≥ 10 mm in diameter if not on systemic immunosuppressive medication or ≥
             5 mm if on systemic immunosuppressive medication;

          -  History of latent TB infection without completion of an appropriate course of
             treatment;

          -  Elective surgery planned from the time of screening through Study Day 168;

          -  At screening blood tests (within 28 days before randomization), any of the following:

               -  AST > 2.5 x upper limit of the normal range (ULN), unless caused by SLE

               -  ALT > 2.5 x ULN, unless caused by SLE

               -  Creatinine > 4.0 mg/dL

               -  Neutrophils < 1,500/mm3

               -  Platelet count < 50,000/mm3

          -  History of any disease, evidence of any current disease (other than SLE), any finding
             upon physical examination, or any laboratory abnormality that, in the opinion of the
             investigator or medical monitor, may compromise the safety of the subject in the study
             or confound the analysis of the study; or

          -  Any employee of the research site who is involved with the conduct of the study.