INCLUSION CRITERIA:
Patients must meet all of the following criteria:
1. Male or female adults greater than or equal to 18 years of age at the time of the first dose of study drug;
2. Written informed consent obtained from the patient or the patient's legal representative;
3. Meet at least 4 of the 11 revised American College of Rheumatology (ACR) classification criteria for SLE (ACR, 1999);
4. Have positive antinuclear antibody test at greater than or equal to 1:80 serum dilution in the past or at screening (prior positive ANA test must be documented via a lab report);
5. Have at least one system with a score of A or two systems with a score of B on the British Isles Lupus Assessment Group (BILAG) index at screening, or have a Safety of Estrogens in Lupus Erythematosus (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score greater than or equal to 6;
6. Sexually active women, unless surgically sterile (including tubal ligation) or at least 2 year post-menopausal must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, diaphragm with spermicide, cervical cap, abstinence, and sterile sexual partner) in addition to the use of a 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. Sexually active men, unless surgically sterile, must likewise practice two effective methods of birth control (condom with spermicide) and must use such precautions from Study Day 0 through the end of the study;
7. Ability to complete the study period, including follow-up period through Study Day 350; and
8. Willing to forego other forms of experimental treatment during study.
EXCLUSION CRITERIA:
1. Have received MEDI-545 within 120 days prior to screening or have either detectable levels of MEDI-545 or anti-MEDI-545 antibodies (positive at greater than I:10 serum dilution) in serum at screening;
2. History of allergy or reaction to any component of the study drug formulation;
3. Weight greater than or equal to 120 kg for patients randomized to Dose Cohorts 1 through 5 or weight greater than or equal to 100 kg for patients randomized to Dose Cohort (6);
4. Have received prednisone greater than 20 mg/day (or an equivalent dose of another oral corticosteroid) within 14 days before randomization/entry;
5. Have received the following dosages of medications within 28 days before randomization/entry: hydroxychloroquine greater than 600 mg/day, mycophenolate mofetil greater than 3 g/day, methotrexate greater than 25 mg/week, leflunomide greater than 20 mg/day, azathioprine greater than 3 mg/kg/day, cyclophosphamide, cyclosporine, or thalidomide;
6. Have received fluctuating doses of antimalarials, mycophenolate mofetil, methotrexate, leflunomide, or azathioprine within 28 days before randomization/entry or fluctuating doses of nonsteroidal anti-inflammatory drugs or oral corticosteroids within 14 days before randomization/entry;
7. Treatment with any investigational drug therapy within 28 days before randomization/entry into the study, B cell-depleting therapies within l2 months before randomization/entry, or biologic therapies within 30 days or 5 half-lives of the biologic agent, whichever is longer, before randomization/entry into the study;
8. In the investigator's opinion, evidence of clinically significant active infection, including ongoing, chronic infection, within 28 days before randomization/entry;
9. 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;
10. Herpes zoster infection within 3 months before randomization/entry;
11. 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;
12. Vaccination with live attenuated viruses within 28 days before randomization/entry;
13. 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);
14. Breastfeeding or lactating women;
15. History of primary immunodeficiency;
16. History of alcohol or drug abuse less than 1 year prior to randomization/entry;
17. History of cancer (except basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy greater than 1 year prior to randomization/entry);
18. History of active tuberculosis (TB) infection or newly positive TB skin test (defined as a reaction greater than or equal to 10 mm in diameter);
19. History of latent tuberculosis infection without completion of an appropriate course of treatment.
20. Elective surgery planned from the time of screening through Study Day 196;
21. At screening blood tests (within 28 days before randomization/entry) any of the following:
-Aspartate aminotransferase (AST) greater than 2 x upper limit of normal range (ULN),
-Alanine aminotransferase (ALT) greater than 2 x upper limit of normal range (ULN),
-Creatinine greater than 4.0 mg dL,
-Neutrophils less than 1,500/mm(3),
-Platelet count less than 50,000/mm(3);
22. 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 patient in the study or confound the analysis of the study; or
23. Any employee of the research site who is involved with the conduct of the study.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/17/2008