Safety and Efficacy of ANX-042 in Human Cardiorenal Syndrome

NCT03019653 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16-001847R01HL084155-06A1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to look at kidney function and hormonal function in patients with a history of heart failure and kidney dysfunction, and to see how the use of a new drug, ANX-042, affects those functions.

Conditions

Heart Failure; Cardiorenal Disease; Renal Disfunction

Outcome Measures

Primary Outcomes (1)

• Change in Glomerular Filtration Rate

  baseline to 3 weeks

Secondary Outcomes (6)

• Change in Sodium Excretion

  baseline to 3 weeks

• Change in Urine Flow

  baseline to 3 weeks

• Change in Blood Pressure

  baseline to 3 weeks

• Change in Renin-angiotensin-aldosterone system (RAAS)

  baseline to 3 weeks

• Change in Urine Annexin A1 (AnxA1) Protein Levels

  baseline to 3 weeks

Study Arms (2)

ANX-042 first, then Placebo

ACTIVE COMPARATOR

In the first intervention period the subjects will receive an infusion of ANX-042. There will be a 3 week washout period. In the second intervention period, the subjects will receive an infusion of placebo

Drug: ANX-042; Drug: Placebo

Placebo first, then ANX-042

ACTIVE COMPARATOR

In the first intervention period the subjects will receive placebo. There will be a 3 week washout period. In the second intervention period, the subjects will receive an infusion of ANX-042.

Drug: ANX-042; Drug: Placebo

Interventions

ANX-042 DRUG

The first 20 subjects will receive a dose 0.003 µg/kg/min by infusion, the next 20 subjects will receive a dose of 0.006 µg/kg/min, then the next 20 subjects will receive 0.01 µg/kg/min.

ANX-042 first, then Placebo; Placebo first, then ANX-042

Placebo DRUG

The pharmacy created a placebo for this study is sterile Dextrose (5%) solution (D5W) 0.9% Sodium Chloride for intravenous administration to match study drug.

ANX-042 first, then Placebo; Placebo first, then ANX-042

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Prior diagnosis of intrinsic renal diseases, such as glomerular nephritis or polycystic kidney disease, including renal artery stenosis of \> 50% (unless revascularized)
• 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
• 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
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
• 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
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Paul M McKie, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 12, 2017
• Study Start: January 1, 2017
• Primary Completion: September 13, 2024
• Study Completion: September 13, 2024
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)