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

NCT00541983 | Completed Phase 1 DMC

• 1 other identifier: X052071
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Type 2 Diabetes

Keywords

Diabetes; Type 2; Mellitus

Outcome Measures

Primary Outcomes (1)

• Glycated hemoglobin (HbA1c) at Days 0 and 28.

  Day 0 and Day 28

Secondary Outcomes (3)

• Pharmacokinetic assessments from serum samples collected at time points specified in the protocol.

  Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364.

• Safety assessed by adverse events, vital signs measurements, clinical laboratory assessments, infusion reactions, immune responses to XOMA 052.

  Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364.

• Assessment of inflammatory markers CRP and ESR collected at time points specified in the protocol.

  Dose groups 1 - 5: Day 0 pre-dose through Day 91. Dose group 6: Day 0 pre-dose through Day 364.

Study Arms (2)

1

ACTIVE COMPARATOR

Drug: XOMA 052

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

XOMA 052 DRUG

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.

1

Placebo DRUG

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.

2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• XOMA (US) LLC: lead

Study Sites (2)

Covance Clinical Research (formerly Swiss Pharma Contract)

Allschwil, Switzerland

Location

Unknown Facility

Zurich, Switzerland

Location

Related Publications (2)

• Cavelti-Weder C, Babians-Brunner A, Keller C, Stahel MA, Kurz-Levin M, Zayed H, Solinger AM, Mandrup-Poulsen T, Dinarello CA, Donath MY. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care. 2012 Aug;35(8):1654-62. doi: 10.2337/dc11-2219. Epub 2012 Jun 14.

  PMID: 22699287 DERIVED

• Cavelti-Weder C, Furrer R, Keller C, Babians-Brunner A, Solinger AM, Gast H, Fontana A, Donath MY, Penner IK. Inhibition of IL-1beta improves fatigue in type 2 diabetes. Diabetes Care. 2011 Oct;34(10):e158. doi: 10.2337/dc11-1196. No abstract available.

  PMID: 21949230 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

gevokizumab

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Pedro Urquilla, MD

  XOMA (US) LLC

  STUDY DIRECTOR

• Marc Donath, MD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 8, 2007
• First Posted: October 10, 2007
• Study Start: September 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: February 1, 2010
• Last Updated: May 4, 2010

Record last verified: 2010-05

Locations

CH (2)