Single-dose, Dose-escalation Study of Safety, PK, and Preliminary Efficacy of XOMA 052 in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of XOMA 052 in subjects with active Type 2 Diabetes Mellitus (T2D). IV administration of XOMA 052 is likely to improve glycemic control in subjects with T2D by blocking certain receptors.

Official Title
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A Phase I, Double-blind, Placebo-controlled, Single-dose, Dose-escalation Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of XOMA 052 in Subjects With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: XOMA 052
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Diabetes Association (ADA) diagnostic criteria for T2D: Fasting blood glucose concentration ≥ 126 mg/dL (≥ 7.0 mmol/L) (must be measured within 28 days prior to Day 0) OR Symptoms of hyperglycemia (e.g., thirst, polyuria, weight loss, visual blurring) AND a casual/random plasma glucose value of ≥ 200 mg/dL (≥ 11.1 mmol/L) (must be measured within 28 days prior to Day 0) HbA1c ≥ 7.5% and ≤ 12% (DCCT standard) Current T2D of duration > 3 months and ≤ 10 years at Screening T2D and other diseases must be stable. Stable disease is defined as disease that is judged stable by the investigator and which did not require a change in medications 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 Weight ≥ 80 lbs (36.3 kg) and ≤ 325 lbs (147.4 kg) BMI ≥ 23 and ≤ 36 kg/m2 For female subjects of child-bearing age, a negative serum pregnancy test. For subjects with reproductive potential, a willingness to utilize adequate contraception 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 Exclusion Criteria: Use of the following medications: Anti-inflammatory therapy other than aspirin ≤ 100 mg/day; Immunosuppressive treatment; Beta 2 and non-selective adrenergic blockers (Note: selective beta 1 blockers are permitted); Thiazolidinediones; Glucagon-like peptide (GLP) agonists including DPP4 inhibitors 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 Fasting C-peptide < 400 pM (< 1.20 μg/L) Hemoglobin < 8.0 g/dL, WBC < 3.0 × 103/mm3, platelet count < 125 × 103/mm3, creatinine > 1.5 mg/dL, AST/ALT > 2 × ULN, alkaline phosphatase > 2 × ULN Positive for GAD65 or IA-2 auto-antibodies History or evidence of thyroid abnormalities, including active hyperthyroidism needing medication. Subjects with hypothyroidism will not be excluded if their TSH level has been normal during the 3 months prior to Screening. Abnormal T3, T4, thyroglobulin, or TSH levels 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, non-metastatic 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 subjects who are pregnant, planning to become pregnant during the course of the study, or breast-feeding History or symptoms of a demyelinating disease Clinically significant diabetic macular edema and/or proliferative diabetic retinopathy by history or fundoscopy 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 Use of a therapeutic monoclonal antibody within 90 days prior to Screening Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to the study drug

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: XOMA 052<br>* Subjects in six successive dose groups will receive a single IV infusion (mg/kg) of study drug on Day 0. The total time of the infusion will be 1 hour ± 15 minutes.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Subjects in six successive dose groups will receive a single IV infusion (mg/kg) of study drug on Day 0. The total time of the infusion will be 1 hour ± 15 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated hemoglobin (HbA1c) at Days 0 and 28. |  | Day 0 and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic assessments from serum samples collected at time points specified in the protocol. |  | Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364. | 
| Safety assessed by adverse events, vital signs measurements, clinical laboratory assessments, infusion reactions, immune responses to XOMA 052. |  | Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364. | 
| Assessment of inflammatory markers CRP and ESR collected at time points specified in the protocol. |  | Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Type 2, Mellitus