Effects of XOMA 052 on Insulin Production in Type 1 Diabetes (LATE STAGE)

A Randomized, Double-blind, Placebo-controlled, Phase 2 Study of the Effects of XOMA 052 on Insulin Production in Subjects With Well-controlled Type 1 Diabetes

To assess the effects of treatment with XOMA 052 on beta-cell function and insulin production in subjects with well-controlled Type 1 diabetes. The safety, tolerability, and pharmacokinetics (PK) of XOMA 052 will also be assessed.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 1
• Intervention / Treatment: Drug: XOMA 052; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 1 diabetes (American Diabetes Association [ADA] criteria) of > 2 year duration that is judged to be stable by the investigator
• No clinically significant change in treatment regimen for T1D (defined as a 20% change) during the 3 months prior to Screening
• Age ≥ 18 years and ≤ 55 years
• HbA1c < 7.5% for the previous two measurements including the measurement taken at Screening (both measurements must occur within 6 months prior to enrollment)
• Positive glutamate decarboxylase-65 (GAD65) and/or IA-2 auto-antibodies
• Body-mass index (BMI) > 18 and < 28 kg/m2
• Willingness to maintain current doses/regimens of vitamins and dietary supplements through the end of the study
• 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. Adequate contraceptive measures include hormonal methods used for two or more cycles prior to Screening (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), double barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, and condom used in conjunction with contraceptive foam or jelly), intrauterine methods (IUD), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence.
• For females receiving hormone replacement therapy (including but not limited to oral contraceptives), must have been on a stable regimen for ≥ 6 months prior to Screening. Hormone therapy must not be initiated during the study

Exclusion Criteria:

• Signs of current infection or history of infection during the 3 months prior to Day 0
• Known to be positive for Hep B surface antigen (HBsAg), Hep C virus (HCV), or HIV
• History of tuberculosis (TB) or positive PPD test. A subject who has had a positive PPD test but has completed a course of treatment for tuberculosis, had a documented vaccination against tuberculosis, or had a negative QuantiFERON®-TB test result is eligible.
• High sensitivity C-reactive protein (hs-CRP) > 10 mg/L
• Presence of foot, leg, or decubitus ulcers
• Neutropenia
• Anemia
• Clinically significant kidney or liver disease
• From 1 week prior to Screening, use of anti-inflammatory therapy other than aspirin ≤ 100 mg/day or up to 5 consecutive days of treatment with non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of an acute illness
• Current immunosuppressive treatment or documented immunodeficiency
• History of severe allergic or anaphylactic reactions
• History of asthma requiring systemic corticosteroid therapy
• Coronary intervention or hospitalization for cardiovascular condition within 12 months prior to Day 0
• Uncontrolled hypertension
• History of congestive heart failure
• History of a coronary event within 12 months prior to Screening
• Female subjects who are pregnant, planning to become pregnant during the course of the study, have recently delivered (within 3 month of Screening), or are breast-feeding
• History of malignancy within 5 years prior to study entry other than carcinoma in situ of the cervix or thyroid, or adequately treated, non-metastatic squamous or basal cell carcinoma of the skin
• Receipt of a live (attenuated) vaccine within 3 months prior to Screening
• Use of any other investigational drug within 30 days prior to enrollment or within 5 half-lives of the investigational drug, whichever is longer
• Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to the study drug
• Any condition (e.g., psychiatric illness) or situation that may compromise the ability of the subject to give written informed consent, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: XOMA 052; 0.3 mg/kg XOMA 052. Beginning on Day 0, each subject will receive one subcutaneous (SC) injection of study drug every 4 weeks for 12 weeks, a total of four injections	Drug: XOMA 052; 0.3 mg/kg XOMA 052. Beginning on Day 0, each subject will receive one subcutaneous (SC) injection of study drug every 4 weeks for 12 weeks, a total of four injections
Placebo Comparator: Placebo; 0.3 mg/kg placebo. Beginning on Day 0, each subject will receive one subcutaneous (SC) injection of study drug every 4 weeks for 12 weeks, a total of four injections	Drug: Placebo; 0.3 mg/kg Placebo. Beginning on Day 0, each subject will receive one subcutaneous (SC) injection of study drug every 4 weeks for 12 weeks, a total of four injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
C-peptide level	incremental AUC over 120 minutes during the MMTT at Day 112 compared to baseline (Day 0 pre-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in insulin requirements	3-day average daily insulin dose at baseline (Day -3 through Day -1) compared to Day 112 (Day 109 through Day 111)
HbA1c levels	from baseline (Day 0 pre-dose) at Day 112
fasting glucose	from baseline (Day 0 pre-dose) at Day 112
fasting glucagon	from baseline (Day 0 pre-dose) at Day 112
cortisol	from baseline (Day 0 pre-dose) at Day 112
markers of systemic inflammation (Interleukin-6, Interleukin-8, Tumor Necrosis Factor α, hs-CRP)	from baseline (Day 0 pre-dose) at Day 112
adipokines	from baseline (Day 0 pre-dose) at Day 112
meal-stimulated Glucagon like peptide-1	AUC over 120 minutes at Day 112 compared to baseline (Day 0 pre-dose)
meal-stimulated gastric inhibitory polypeptide	AUC over 120 minutes at Day 112 compared to baseline (Day 0 pre-dose)
lipids profile	from baseline (Day 0 pre-dose) at Day 112
Change in fatigue according to the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire	from baseline at Day 112
Anti XOMA 052 Antibodies	from baseline (Day 0 pre-dose) at Day 112
Number of Adverse Events	from baseline (Day 0 pre-dose) at Day 364

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: XOMA (US) LLC
• Investigators: Study Chair: Marc Donath, Prof., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: February 1, 2013
• First Submitted That Met QC Criteria: February 6, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Estimate): February 11, 2014
• Last Update Submitted That Met QC Criteria: February 10, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: EK-189/10