Safety and Efficacy of ANX-042 in Human Cardiorenal Syndrome

Prior treatment

• Prior diagnosis of intrinsic renal diseases, such as glomerular nephritis or polycystic kidney disease, including renal artery stenosis of \> 50% (unless revascularized)
• Have received an investigational drug within 1 month prior to dosing

Other illness

• Myocardial infarction within 6 months of screening
• Unstable angina within 6 months of screening, or any evidence of acute myocardial ischemia
• Significant valvular stenosis (greater than moderate in severity) , hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
• Severe congenital heart diseases
• Second or third degree heart block without a permanent cardiac pacemaker
• Stroke within 3 months of screening, or other evidence of significantly compromised central nervous system (CNS) perfusion
• Patients with an allergy to iodine

Lab values

• Alanine transaminase (ALT) \>2 times the upper limit of normal
• Serum sodium of \< 125 milliequivalent/dL (mEq/dL) or \> 160 mEq/dL
• Serum potassium of \< 3.0 mEq/dL or \> 5.7 mEq/dL
• Hemoglobin \< 8.5 gm/dl
• Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data

Other

• Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
• Hospitalization for decompensated CHF during the past 6 months
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
• Female subject who is pregnant or breastfeeding
• In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons
• Documented systolic blood pressure less than 90 mmHg at consent visit

• Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months. If assessment is greater than 12 months old, hand-held echocardiogram (ECHO) determination will be performed at consent visit once enrolled.
• Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months, on stable doses of furosemide, angiotensin-converting enzyme (ACE) inhibitor or angiotensin II type 1 (AT1) blocker, beta blocker, or aldosterone antagonist over the last 4 weeks and no episode of decompensated Congestive Heart Failure (CHF) over the past 6 months.
• Calculated creatinine clearance of equal or less than 89 ml/min and greater than 20 ml/min, using the Modification of Diet in Renal Disease (MDRD) formula assessed within the past 48 months and a confirmatory calculated creatinine clearance equal or less than 89 ml/min and greater than 20 ml/min at the time of enrollment.
• Digoxin, antiarrhythmic medications and other vasodilators will be allowed; however, all medications must be at stable doses 4 weeks prior to enrollment. Subjects taking non-steroidal anti-inflammatory drugs (NSAIDs), except aspirin, will not be able to increase their medication dose for the duration of the study.