A Study to Evaluate Safety and Tolerability of Multiple Doses of MEDI-546 in Adult Subjects with Scleroderma - MEDI-546

Exclusion Criteria

• - History of allergy or reaction to any component of the MEDI-546 formulation;
• - Forced vital capacity (FVC) < 60% predicted, diffusing capacity for carbon monoxide (DLCO) < 40% predicted, pulmonary hypertension requiring treatment with endothelin receptor antagonists or prostacyclin analogues, scleroderma renal crisis within the last year, or medically significant malabsorption;
• - Have received the following medications within 28 days before entry:
• • Cyclophosphamide at any dose
• • Systemic 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 leflunomide > 20 mg/day within 6 months before entry;
• - Have received fluctuating doses of the following within 28 days before entry:
• • Antimalarials
• • Mycophenolate mofetil
• • Methotrexate
• • Leflunomide
• • Azathioprine;
• - Have received prednisone > 20 mg/day or in fluctuating doses within 14 days before entry;
• - Have received fluctuating doses of nonsteroidal anti-inflammatory drugs (NSAIDs) within 14 days before entry;
• - Treatment with any investigational drug therapy within 28 days before entry into the study, B cell-depleting therapies within 12 months before entry, or biologic therapies within 30 days or 5 half-lives of the biologic agent, whichever is longer, before entry into the study;
• - In the investigator's opinion, evidence of clinically significant active infection, including ongoing, chronic infection, within 28 days before entry;
• - A history of severe viral infection as judged by the investigators, including severe infections of either cytomegalovirus (CMV) or the herpes family such as disseminated herpes, herpes encephalitis, ophthalmic herpes;
• - Herpes zoster infection within 3 months before entry;
• - 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 entry;
• - Pregnancy (women, unless surgically sterile or at least 2 years post-menopausal, must have a negative serum pregnancy test within 28 days before receiving MEDI-546 and a negative urine pregnancy test on days of MEDI-546 administration before receiving MEDI-546);
• - Breastfeeding or lactating women;
• - History of primary immunodeficiency;
• - History of alcohol or drug abuse < 1 year prior to entry;
• - 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 entry;
• - History of active tuberculosis (TB) infection or latent TB infection without completion of an appropriate course of treatment;
• - 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) without concomitant prophylactic therapy;
• - Elective surgery planned from the time of signing of the informed consent through end of study;
• - At screening blood tests (within 28 days before entry), any of the following:
• • Aspartate aminotransferase (AST) > 2.5 x upper limit of the normal range (ULN), unless due to Myositis
• • Alanine aminotransferase (ALT) > 2.5 x ULN
• • Creatinine > 4.0 mg/dL
• • 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 scleroderma), any finding upon physical examination, chest x-ray, 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.
• - History of vasculitis.