Subcutaneous Administration of Otelixizumab to T1DM Patients

Inclusion Criteria

• •Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• •A female subject is eligible to participate if she is of:
• •Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 mIU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section TBC if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• •Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 to sufficiently minimize the risk of pregnancy. Female subjects must agree to use contraception for at least 2 weeks prior to dosing and for at least 60 days after dosing.
• •Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 2 weeks after dosing.
• •Body weight \> or = 50 kg and BMI within the range 18 - 30 kg/m2 (inclusive).
• •Confirmed diagnosis of insulin-requiring T1DM according to the America Diabetes Association criteria and on a relatively stable insulin regimen, with HbAlc \> or = 9%.
• •Positive for at least one of the following T1DM-related autoantibodies: anti-GAD (glutamic acid decarboxylase) and/or anti IA 2A.
• •Random plasma C-peptide level must be above the level of assay detection at Screen. NOTE: If the screening random plasma C-peptide level is undetectable, subjects must have a Mixed Meal Stimulated C-peptide (MMSCP) equal to or greater than 0.15 nmol/L (0.45 ng/mL) to be eligible for study participation.
• •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• •Average QTcB \< 450 msec.
• •No history of splenectomy.
• •Subject is seropositive for EBV with \< 10,000 copies of EBV DNA per 106 lymphocytes as determined by quantitative polymerase chain reaction.
• •CD4+ lymphocyte counts within normal limits within the 30 days before the first dose of study drug.
• •Chest X-ray with negative finding at screening
• •The subject has no current or prior malignancy, other than non-melanoma skin cancer (subject must have had fewer than 5 occurrences of non-melanoma skin cancer, and the last occurrence must not be within 3 months of study entry).
• •Laboratory tests normal at screening or judged not clinically significant by the investigator (except for labs relating to T1DM which may include but not limited to HbA1C and glucose).