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

This study has been completed.
Sponsor:
Information provided by:
XOMA (US) LLC
ClinicalTrials.gov Identifier:
NCT00541983
First received: October 8, 2007
Last updated: May 2, 2010
Last verified: May 2010

October 8, 2007
May 2, 2010
September 2007
July 2009   (final data collection date for primary outcome measure)
Glycated hemoglobin (HbA1c) at Days 0 and 28. [ Time Frame: Day 0 and Day 28 ] [ Designated as safety issue: No ]
  • Safety
  • Pharmacokinetics
Complete list of historical versions of study NCT00541983 on ClinicalTrials.gov Archive Site
  • Pharmacokinetic assessments from serum samples collected at time points specified in the protocol. [ Time Frame: Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364. ] [ Designated as safety issue: No ]
  • Safety assessed by adverse events, vital signs measurements, clinical laboratory assessments, infusion reactions, immune responses to XOMA 052. [ Time Frame: Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364. ] [ Designated as safety issue: No ]
  • Assessment of inflammatory markers CRP and ESR collected at time points specified in the protocol. [ Time Frame: Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364. ] [ Designated as safety issue: No ]
  • Inflammatory markers (CRP and ESR)
  • HbA1c
Not Provided
Not Provided
 
Single-dose, Dose-escalation Study of Safety, PK, and Preliminary Efficacy of XOMA 052 in Type 2 Diabetes Mellitus
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

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes
  • Drug: XOMA 052
    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.
  • Drug: Placebo
    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.
  • Active Comparator: 1
    Intervention: Drug: XOMA 052
  • Placebo Comparator: 2
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
February 2010
July 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT00541983
X052071
Yes
Pedro Urquilla, MD, XOMA (US) LLC
XOMA (US) LLC
Not Provided
Study Director: Pedro Urquilla, MD XOMA (US) LLC
Principal Investigator: Marc Donath, MD University of Zurich
XOMA (US) LLC
May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP