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

Inclusion Criteria

• Male or female aged between 16 and 27 years of age inclusive, at the time of signing the informed consent.

NOTE: Subjects aged 16 to 17 years must be Tanner Stage >= 2. All subjects must weigh at least 31 kg.

• Diagnosis of diabetes mellitus (DM) according to Amerrican Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus (T1DM), with an interval of approximately 28 days (not more than 32 days) between the initial diagnosis and the first dose of study drug). Written documentation of the diagnosis of DM, including the date of diagnosis, must be obtained from the diagnosing physician.
• Currently requires insulin treatment for T1DM and has received intensive insulin therapy for at least 7 days prior to screening.
• Positive for at least one auto-antibody associated with T1DM: antibody to glutamic acid decarboxylase (anti GAD), antibody to protein tyrosine phosphatase-like protein (anti IA 2), antibody to islet-cell antigen (ICA) or ZnT8 Autoantibody.
• Evidence of residual functioning Beta-cells as measured by mixed meal stimulated C peptide peak level >= 0.2 nanomole/litre (nmol/L).
• A female subject is eligible to participate if she has a negative pregnancy test as determined by a urine hCG test at screening or prior to dosing and agrees to use one of the contraception methods listed in study protocol. Female subjects must agree to use contraception for 2 weeks prior to dosing and for 60 days after the last dose of study drug or has only same-sex partners (refrains from heterosexual intercourse), when this is her preferred and usual lifestyle.
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in study protocol. This criterion must be followed from 2 weeks prior to dosing and for 60 days after the last dose of study drug.
• Willing to follow the procedures outlined in the protocol.
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 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