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

Study Overview
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Brief Summary
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The purpose of this study is to determine if T2-18C3, a true human monoclonal antibody that blocks inflammation, is safe to use in patients with type 2 diabetes. The study will also be looking at the ability of T2-18C3 to improve control of blood sugar levels in diabetics by blocking inflammation in the pancreas.

Detailed Description
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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.

Official Title
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A Phase II Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of an Anti-Inflammatory Therapeutic Antibody (MABp1) in Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: T2-18C3 therapeutic antibody


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T2-18C3 therapeutic antibody<br>9 subjects will receive the T2-18C3 therapeutic antibody. | Drug: T2-18C3 therapeutic antibody<br>* 1.25 mg/kg Intravenous infusion every 2 weeks for a total of 4 doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | The safety and tolerability of T2-18C3 will be determined by observing patients for clinical adverse events, changes in vital signs, and changes in laboratory parameters such as hematology and chemistry. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | Serum levels of T2-18C3 will be measured in patients | 90 days | 
| Preliminary Efficacy | The ability of T2-18C3 to improve glycemic control will be measured by comparing the change in glycosylated hemoglobin levels of patients from baseline to day 90. | 90 days |