A Two-Stage Randomized Placebo-controlled Ascending Dose Phase I/ IIa Study to Evaluate Safety, Tolerability, Pharmacodynamic Effects and Preliminary Efficacy of an Anti-Interleukin 1 beta Vaccine (CYT013-IL1bQb) in Patients with Type 2 Diabetes Mellitus.
- Conditions
- adult patients with type 2 diabetes mellitusMedDRA version: 9.1Level: LLTClassification code 10012601Term: Diabetes mellitus
- Registration Number
- EUCTR2008-007012-15-DE
- Lead Sponsor
- Cytos Biotechnology AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 122
• Diagnosis of type 2 diabetes mellitus, according to the American Diabetes Association diagnostic criteria, = 3 months at time of randomization
• Stage I: HbA1c in the range of 6.5 - 9.5% (inclusive) at screening/ Stage II: HbA1c in the range of 7.0 – 9.5 % (inclusive)
• = 18 < 70 years of age at the time of randomization
• Fasting plasma glucose < 13.4 mmol/L (< 240 mg/dL) at screening
• Male patients or female patients without childbearing potential. Postmenopausal (at least one year without menstrual period, in case of doubts serum FSH should be determined and must be >30 U/L) or surgically sterilized (documentation required).
• BMI = 23 kg/m2 and < 40 kg/m2 at screening, and, per patient self-report, following their regular weight maintenance or reduction diet for the management of diabetes for at least 4 weeks prior to randomization
• Treatment with diet and exercise alone or a stable dose of metformin, or sulfonylurea, or metformin plus a sulfonylurea for at least 4 weeks prior to randomization
• Subject is able and willing to comply with the study's visit requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
• Positive for GAD65 or IA-2 auto-antibodies
• Symptoms of hyperglycemia (i.e. polyuria and polydypsia) in the opinion of the investigator
• History of significant weight gain or loss (+/- 5%) during the 4 weeks before randomization
• Fasting C-peptide level < 400 pmol/L at screening
• Change in the medicamentous treatment of elevated blood pressure, diabetes mellitus or dyslipidemia within 4 weeks prior to the randomization
• Use of any weight loss medication (over the counter prescription) or initiation of a prescribed weight management or exercise program within 4 weeks before randomization
• Uncontrolled arterial hypertension defined as diastolic pressure >95 mmHg and/or systolic >170 mmHg
• Evidence of active infection, CRP > 30 mg/L, history of recent infection or of chronic infection requiring treatment with anti-infectives, hospitalization or therapy with antibiotics within 4 weeks prior to randomization
• History of tuberculosis or tuberculosis exposure; positive test result in a tuberculosis- specific Interferon gamma release assay at screening
• Active leg or foot ulcer
• Persistent asthma or COPD treated with inhalative corticosteroids
• Known proliferative retinopathy or macular edema
• White blood cell (leucocytes) count at screening < 3.5 x 10^9/L
• Absolute neutrophils count at screening < 1.5 x 10^9/L
• Platelets < 150 x 10^9/L at screening
• Hemoglobin at screening <11.0 g/dL for female and <12.0 g/dL for male
• Elevated ALT or AST or GGT or ALP at screening (greater than 2.0 x the upper limit of normal)
• Serum creatinine at screening >107 mcmol/L for female and >115 mcmol/L for male
• Estimated glomerular filtration rate (eGFR) at screening < 60 mL/min as calculated via the abbreviated MDRD equation (Modification of Diet in Renal Disease study group)
• U-ACR (albumin to creatinine ratio in spot urine) > 50 mg/g creatinine
• Malignancy (present or in anamnesis), with the following exceptions: non-invasive basal cell carcinoma (basaliom) of the skin in anamnesis or carcinoma in situ of cervix uteri in anamnesis
• Current systemic anti-inflammatory therapy other than aspirin = 100 mg/day or immunosuppressive treatment, in particular oral corticosteroids
• Receipt of any biologic or immunosuppressive therapy (experimental or commercial), including anakinra (Kineret®), IL-1 beta blocking monoclonal antibodies, soluble IL-1 receptor or any tumor necrosis factor (TNF) blocking agents (eg, etanercept and infliximab), within 3 months of randomization
• Antidiabetic medication other than metformin, sulfonylurea
• Planned prophylactic immunization with live vaccines 3 months prior to screening or during the study (including Follow Up)
•Planned active immunization with other (than live vaccines) prophylactic vaccines within 2 weeks before or 2 weeks after any application of study medication
• Use of an investigational medicinal product within 30 days before enrolment, or planned use during the whole study period
• Known autoimmune disease
• Severe allergy
• Pregnancy or breastfeeding
• Women of childbearing age that are not surgically sterilized
• Patients with a history or current positive test for HIV infection, AIDS, or other immunosuppressive disorders; hepatitis B or C
• Presence of suspicious lymphadenopathy or splenomegaly on physical examination
• Drug or alcohol abuse within the past 2 years before screening
• Presence or history of relevant cardiovascular disease (myocardial infarction
<6 months before r
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: na;Primary end point(s): Primary outcome measures are safety, tolerability and immunogenicity of CYT013-Il1bQb throughout the study. ;Main Objective: • To evaluate safety and tolerability of up to 4 different dose regimens of CYT013-IL1bQb in patients with type 2 diabetes mellitus<br>• To assess pharmacodynamic effects and dose-response (immunogenicity and biomarkers) of up to 4 dose regimens of CYT013-IL1bQb in patients with type 2 diabetes mellitus<br>• To explore preliminary clinical efficacy (effects on fasting plasma glucose, HbA1c) of CYT013-IL1bQb in patients with type 2 diabetes mellitus<br>
- Secondary Outcome Measures
Name Time Method