Safety and Pharmacokinetics Study of XOMA 052 in Subjects With Type 2 Diabetes Mellitus

Phase 1

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: XOMA 052; Drug: Placebo

• Registration Number: NCT00513214
• Lead Sponsor: XOMA (US) LLC

Brief Summary

The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of XOMA 052 in subjects with stable Type 2 Diabetes Mellitus (T2D).

The study is a dose-escalation study designed to evaluate route of administration (intravenous or subcutaneous), doses, and dosing regimens for future studies.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-08-07
• Study First Submitted QC: 2007-08-07
• Study First Posted: 2007-08-08
• Primary Completion: 2009-06
• Study Completion: 2010-02
• Status Verified: 2011-09
• Last Update Submitted: 2011-09-30
• Last Update Posted: 2011-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

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 35 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 35 days prior to Day 0)
• HbA1c ≥ 7.5% and ≤ 12% (DCCT standard)
• Current T2D of duration > 6 months 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 35 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 ≤ 40 kg/m2
• For female subjects of child-bearing age, a negative serum pregnancy test. For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study.
• Agree 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 35 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 X 103/mm3, platelet count < 125 X 103/mm3, creatinine > 1.5 mg/dL, AST/ALT > 2 X ULN, alkaline phosphatase > 2 X ULN
• Positive for GAD65 or IA-2 auto-antibodies
• 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 35 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
XOMA 052	XOMA 052	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Safety assessed by pre- and post-treatment serial measurements of vital signs.	Part 1: Day 0 pre-treatment through Day 56. Part 2: Day 0 pre-treatment through Day 56. Part 3: Day 0 pre-treatment through Day 84.
Safety assessed by treatment-emergent adverse events.	Part 1: Day 0 post-treatment through Day 56. Part 2: Day 0 post-treatment through Day 56. Part 3: Day 0 post-treatment through Day 84.