Type 2 Diabetes
Conditions
Keywords
Diabetes, Type 2, Mellitus
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.
Interventions
DRUGXOMA 052
* Part 1, Single IV infusion at one of six dose levels (mg/kg). * Part 2, Single SC injection at one of three dose levels (mg/kg). * Part 3, Three biweekly SC injections at one of two dose levels (mg/kg).
DRUGPlacebo
* Part 1, Single IV infusion at one of six dose levels (mg/kg). * Part 2, Single SC injection at one of three dose levels (mg/kg). * Part 3, Three biweekly SC injections at one of two dose levels (mg/kg).
Sponsors
XOMA (US) LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. |
Countries
United States
Outcome results
None listed