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

Type 2 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00541983
• Other study ID #: X052071
• Status: Completed
• Phase: Phase 1
• First received: October 8, 2007
• Last updated: May 2, 2010
• Start date: September 2007
• Est. completion date: February 2010

Study information

• Verified date: May 2010
• Source: XOMA (US) LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: February 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

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
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.

Locations

Country	Name	City	State
Switzerland	Covance Clinical Research (formerly Swiss Pharma Contract)	Allschwil

Sponsors (1)

Lead Sponsor	Collaborator
XOMA (US) LLC

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycated hemoglobin (HbA1c) at Days 0 and 28.		Day 0 and Day 28	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No