Clinical trial NCT01788033: Effects of XOMA 052 on Insulin Production in Type 1 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus Type 1
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: XOMA (US) LLC
First posted: 2013-02-11
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: C-peptide level
timeFrame: incremental AUC over 120 minutes during the MMTT at Day 112 compared to baseline (Day 0 pre-dose
Secondary outcomes:
measure: Change in insulin requirements
timeFrame: 3-day average daily insulin dose at baseline (Day -3 through Day -1) compared to Day 112 (Day 109 through Day 111)
measure: HbA1c levels
timeFrame: from baseline (Day 0 pre-dose) at Day 112
measure: fasting glucose
timeFrame: from baseline (Day 0 pre-dose) at Day 112
measure: fasting glucagon
timeFrame: from baseline (Day 0 pre-dose) at Day 112
measure: cortisol
timeFrame: from baseline (Day 0 pre-dose) at Day 112
measure: markers of systemic inflammation (Interleukin-6, Interleukin-8, Tumor Necrosis Factor α, hs-CRP)
timeFrame: from baseline (Day 0 pre-dose) at Day 112
measure: adipokines
timeFrame: from baseline (Day 0 pre-dose) at Day 112
measure: meal-stimulated Glucagon like peptide-1
timeFrame: AUC over 120 minutes at Day 112 compared to baseline (Day 0 pre-dose)
measure: meal-stimulated gastric inhibitory polypeptide
timeFrame: AUC over 120 minutes at Day 112 compared to baseline (Day 0 pre-dose)
measure: lipids profile
timeFrame: from baseline (Day 0 pre-dose) at Day 112
measure: Change in fatigue according to the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire
timeFrame: from baseline at Day 112
measure: Anti XOMA 052 Antibodies
timeFrame: from baseline (Day 0 pre-dose) at Day 112
measure: Number of Adverse Events
timeFrame: from baseline (Day 0 pre-dose) at Day 364
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Marc Donath, Prof.
role: STUDY_CHAIR
References: