A Study of the Safety and Pharmacokinetics of an Anti-Inflammatory Therapeutic Antibody (MABp1) in Patients With Type 2 Diabetes

This is a phase I, open label study of the safety and pharmacokinetics of T2-18C3 in patients with T2D. Nine patients will receive four biweekly IV infusions of the study drug, T2-18C3, at a dose level of 1.25 mg/kg. These patients will be followed for a total of 90 days to examine safety, pharmacokinetics, and preliminary efficacy.

Inclusion criteria

• American Diabetes Association (ADA) diagnostic criteria for Type 2 Diabetes (T2D)
• HbA1c >7.0% and ≤ 10%
• Current T2D duration > 3 months at Screening
• T2D and other diseases must be stable. Stable disease is defined as disease which did not require a change in medication or dosing level on 4 or more consecutive days or 7 days in total within 28 days prior to Day 0.
• Age ≥ 18 and ≤ 70 at Screening
• BMI ≥ 23 and ≤ 40 kg/m2
• For female patients of child-bearing age, a negative serum pregnancy test. For patients with reproductive potential, a willingness to utilize adequate contraception (oral contraception plus a mechanical barrier) and not become pregnant (or have their partner[s] become pregnant) during the study
• Agrees not to change diet and exercise regimen during the trial
• Signed and dated Ethics Committee (EC) approved informed consent before any protocol-specific screening procedures are performed

Exclusion criteria

• Use of the following medications:

• Daily use of steroids or aspirin ≥ 700 mg per week
• Immunosuppressive treatment
• Thiazolidinediones
• Concomitant treatment with any other therapeutic antibody, or treatment with any biologic agent that blocks the IL-1 or TNFα signaling pathway
• Change in medication for diabetes within 28 days prior to Day 0, defined as a change in dosing level on 4 or more consecutive days or 7 days in total
• Hemoglobin <10.0 g/dL, WBC <3.0 x 103/mm3 , platelet count <125 x 103/mm3, creatinine > 1.5mg/dL, AST/ALT >2 x ULN, alkaline phosphatase >2 x ULN
• Abnormal, untreated T3, T4, thyroglobulin, or TSH levels or history of Grave's disease
• Known HIV antibody, hepatitis B surface antigen and/or hepatitis C antibody
• History of malignancy within 5 years prior to study entry other than carcinoma in situ of the cervix, or adequately treated, nonmetastatic squamous or basal cell carcinoma of the skin
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of tuberculosis, positive PPD test, active atopic disease requiring medication, or asthma
• Infectious disease:

• CRP >30 mg/L, fever, or infection requiring treatment with antibiotics within 3 weeks prior to Screening
• History of recurrent infection or predisposition to infection
• Active leg or foot ulcer
• Immunodeficiency
• Female patients who are pregnant, planning to become pregnant during the course of the study, or breast-feeding
• Receipt of a live (attenuated) vaccine within 3 months prior to Screening
• Major surgery within 28 days prior to Day 0
• Participation in an investigational drug or device trial within 30 days prior to Screening