Investigation of Otelixizumab in New-Onset, Autoimmune Type 1 Diabetes Mellitus Patients

Exclusion Criteria

• •A positive pre-study Hepatitis B surface antigen or core antibody or positive Hepatitis C antibody result within 3 months of screening
• •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• •A positive test for Human Immunodeficiency Virus (HIV) 1 and/or 2 antibody.
• •The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• •Exposure to more than four new investigational drugs within 12 months prior to the first dosing day.
• •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.
• •Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 3 month period.
• •Lactating females.
• •Subject is mentally or legally incapacitated.
• •History of thrombocytopenia.
• •The subject has received immunizationion with a vaccine within 4 weeks before the first dose of study drug or requires a vaccine within 30 days after the last dose of study drug
• •The subject has had significant systemic infection during the 6 weeks before the first dose of study drug (e.g., infection requiring hospitalization, major surgery, or intravenous (i.v.) antibiotics to resolve; other infections, e.g., bronchitis, sinusitis, localized cellulitis, candidiasis, or urinary tract infections, must be assessed on a case-by-case basis by the investigator regarding whether they are serious enough to warrant exclusion).
• •Current or prior malignancy, other than non-melanoma skin cancer.
• •Patient has undergone a splenectomy
• •Radiological evidence of active tuberculosis (TB).
• •Significant and/or active disease in any body system likely to increase the risk to the subject or interfere with the subject's participation in or completion of the study. Examples of significant diseases include, but are not limited to, coronary artery disease, congestive heart failure, uncontrolled hypertension, renal failure, emphysema, history of bleeding peptic ulcers, history of seizure(s), addiction to illicit drugs, and alcohol abuse.
• •Clinically significant (based on Investigator's discretion in consultation with the Medical Monitor if second opinion required) abnormal laboratory values during the Screening period, other than those due to T1DM. A clinically significant abnormal value will not result in exclusion if, upon re test, the abnormality is resolved or becomes clinically insignificant.
• •Positive EBV capsid Ab IgM in absence of a positive EBV EBNA Ab IgG
• •EBV viral load of\> 10,000 copies per 10\^6 peripheral blood mononuclear cells (PBMCs) as determined by quantitative polymerase chain reaction (qPCR)
• •Immunoglobulin G (IgG) negative for EBV.
• •A positive result on an Immuno-Assay test for syphilis; and, if result of Immuno-assay test is positive, then a confirmatory test will be performed.
• •Have used any atypical antipsychotic drug (e.g., risperidone, quetiapine, or clozapine) within the 30 days before signing the Informed Consent Form (ICF).
• •Have previously received otelixizumab or any other anti cluster of differentiation (CD)3 monoclonal antibody, e.g. muromonab, or teplizumab, and are not willing to refrain from using any such antibody for the planned duration of study participation (2 years after the last dose of study drug).
• •Previous or current exposure to biologic cell-depleting therapies (e.g. anti-CD11a, anti-CD22, anti-CD20, anti- B lymphocyte stimulator/ B-cell activating factor (BLyS/BAFF), anti-CD3, anti-CD5, anti-CD52) including investigational agents, and planning to use any such antibody for the planned duration of study participation (2 years after the last dose of study drug).
• •Predisposition to thromboembolic disease, or thromboembolic event (excluding superficial) in the past 12 months.
• •Is currently receiving corticoid treatment or has received systemic corticoid treatment within a month of screening,
• •History of Graves disease
• •Prior allergic reaction, including anaphylaxis, to any human, humanised, chimeric, or rodent antibody.
• •Have undergone any major surgical procedure within 30 days before the first dose of study drug, and/or planning to undergo any such surgery within 3 months after the last dose of study drug.
• •Any condition or situation that, in the investigator's judgment, is likely to cause the subject to be unable or unwilling to participate in study procedures or to complete all scheduled assessments.