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
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Drug: XOMA 052
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by XOMA (US) LLC:

Primary Outcome Measures:
  • Glycated hemoglobin (HbA1c) at Days 0 and 28. [ Time Frame: Day 0 and Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 36
Study Start Date: September 2007
Study Completion Date: February 2010
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 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.
Placebo Comparator: 2 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00541983

Locations
Switzerland
Covance Clinical Research (formerly Swiss Pharma Contract)
Allschwil, Switzerland
Zurich, Switzerland
Sponsors and Collaborators
XOMA (US) LLC
Investigators
Study Director: Pedro Urquilla, MD XOMA (US) LLC
Principal Investigator: Marc Donath, MD University of Zurich
  More Information

No publications provided by XOMA (US) LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pedro Urquilla, MD, XOMA (US) LLC
ClinicalTrials.gov Identifier: NCT00541983     History of Changes
Other Study ID Numbers: X052071
Study First Received: October 8, 2007
Last Updated: May 2, 2010
Health Authority: Switzerland: Swissmedic

Keywords provided by XOMA (US) LLC:
Diabetes
Type 2
Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 23, 2014