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

A Phase 1/2a, Double-blind, Placebo-controlled Study of the Safety and Pharmacokinetics of XOMA 052 in Subjects With Type 2 Diabetes Mellitus

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: XOMA 052; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Escondido, California, United States, 92026
  • Florida
    • Miami Gardens, Florida, United States, 33169
  • Nebraska
    • Omaha, Nebraska, United States, 68154
  • Texas
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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).
Active Comparator: XOMA 052	Drug: XOMA 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).

What is the study measuring?

Primary Outcome Measures

Outcome 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.

Collaborators and Investigators

• Sponsor: XOMA (US) LLC
• Investigators: Study Director: Pedro Urquilla, MD, XOMA (US) LLC

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: August 7, 2007
• First Submitted That Met QC Criteria: August 7, 2007
• First Posted (Estimate): August 8, 2007

Study Record Updates

• Last Update Posted (Estimate): October 4, 2011
• Last Update Submitted That Met QC Criteria: September 30, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Diabetes; Type 2; Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: X052073