NOX-E36 in Patients With Type 2 Diabetes Mellitus and Albuminuria

Study Overview
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Brief Summary
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Primary objective: - To characterize the effects of 12 weeks treatment with study drug on albumin-creatinine ratio (ACR) in patients with type 2 diabetes and albuminuria Secondary objectives: To characterize the effect of study drug on glycosylated hemoglobin fraction (HbA1c) To evaluate the effect of study drug on markers of glycemic disorders, systemic inflammation, renal and liver disease and cardiovascular function To assess the safety and tolerability of study drug To determine the population pharmacokinetics (PK) of study drug

Official Title
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A Phase IIa Study to Characterize the Effects of CCL2 Inhibition With the Spiegelmer® NOX-E36 in Patients With Type 2 Diabetes Mellitus and Albuminuria

Conditions
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Type 2 Diabetes Mellitus, Albuminuria

Intervention / Treatment
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* Drug: NOX-E36


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus according to American Diabetes Association (ADA) definition Age ≥ 18 HbA1c between 6.0% and 10.5%, inclusive ACR > 100 mg/g calculated 3 times in first morning void urine, at least 2 of the measurements > 100 mg/g Patients on stable (unchanged medication for at least 3 months) treatment to control hypertension, hyperglycemia and (if applicable) dyslipidemia Stable treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or Angiotensin II receptor blockers (ARBs) (renin-angiotensin system [RAS] blockade) Willing and able to understand and sign an approved Informed Consent form Men must agree to follow accepted birth control methods during treatment and for 3 months after completion of treatment. Women must be of non-childbearing potential. Exclusion Criteria: Type 1 diabetes mellitus Estimated Glomerular Filtration Rate (eGFR) ≤25 mL/min/1.73m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) Recent cardiovascular events (3 months) Uncontrolled hypertension (upper limits 180/110 mmHg) Dialysis and/or acute kidney injury within 3 months before screening Significant edema, infectious diseases, leg ulcers Severe concurrent disease which, in the judgment of the investigator, would interfere significantly with the assessments of safety and efficacy during this study Treatment with any other investigational agent, or participation in another clinical study within 90 days prior to baseline visit Patient with known infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C In the judgment of the clinical investigator, clinically significant abnormal laboratory values at the screening visit Use of thiazolidinedione class drugs, immune suppressants, steroid therapy (except for topical use or inhalation), chronic use of non-steroidal anti-inflammatory drug (NSAIDs), cyclooxygenase type 2 (COX-2) inhibitors, two or more diuretic drugs and/or aliskiren In the judgment of the clinical investigator, patients who are likely to be non-compliant or uncooperative during the study. Previous participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NOX-E36<br> | Drug: NOX-E36<br>* 0.5 mg/kg study drug or placebo as SC injections twice a week<br>|
| Placebo Comparator: Placebo<br> | Drug: NOX-E36<br>* 0.5 mg/kg study drug or placebo as SC injections twice a week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of NOX-E36 on albuminuria as measured by ACR (albumin to creatinine ratio; mg/g) | ACR calculated in first morning void urine; comparison of patients treated with NOX-E36 versus placebo | Change versus baseline after 12 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of NOX-E36 on hsCRP | Comparison of patients treated with NOX-E36 versus placebo | Change versus baseline after 12 weeks treatment | 
| Effect of NOX-E36 on HbA1C | Comparison of patients treated with NOX-E36 versus placebo | Change versus baseline after 12 weeks treatment | 
| Effect of NOX-E36 on HOMA-IR | Comparison of patients treated with NOX-E36 versus placebo | Change versus baseline after 12 weeks treatment | 
| Effect of NOX-E36 on eGFR | eGFR will be calculated by the CKD-EPI equation using creatinine and cystatin C Comparison of patients treated with NOX-E36 versus placebo | Change versus baseline after 12 weeks treatment |