NCT04216342

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers

An Intravenous, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 64 (estimated)
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) · NIH
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Accepted

Summary

Background: Heart disease is the leading cause of death, disability, and healthcare expense in the United States. Researchers think a new drug called Fx-5A may be useful to treat different cardiovascular diseases and inflammation. Objective: To understand the safety, tolerability, and effects of Fx-5A. Eligibility: Healthy people ages 18 and older who are not pregnant Design: Participants will be screened with: Medical history Physical exam Blood tests Pregnancy test for female participants Participants will stay in the hospital for 36-48 hours. This will include: Blood tests EKGs: Electrodes will be placed on the participant s chest. The patches are connected to cables that will send information from their heart to a machine. Single infusion of Fx-5A. A needle will be used to insert a plastic tube into a vein in the participant s arm. This tube will remain in the arm for the duration of the hospital stay for blood tests. Participants will have follow-up visits day 7 and day 28 after their infusion. At these visits, they will have blood tests and an EKG. Participation will last 5-10 weeks.

Detailed description

Cardiovascular disease (CVD) is one of the leading causes of death worldwide and elevated levels of cholesterol and triglycerides on plasma lipoproteins are major contributing risk factors. Therapeutic agents that increase High Density Lipoproteins (HDL) may be useful additions to our current treatment approaches for preventing coronary heart disease (CHD), because while existing drugs lower Low Density Lipoproteins (LDL), they do not fully prevent CHD. A potential new CHD treatment strategy has recently been described called Acute HDL Therapy, which involves weekly intravenous infusions of HDL, or HDL components (i.e. ApoA-I), or HDL mimetics into patients suffering from the acute coronary syndrome. In early stage clinical trials, a 5-week course of this therapy has been shown to rapidly reduce atherosclerotic plaques, as assessed by intravascular ultrasound. The goal of Acute HDL Therapy is to rapidly stabilize patients at significant risk for developing myocardial infarction, while concurrently starting them on conventional lipid lowering drugs and other agents already known to reduce the risk of myocardial infarction. This clinical research project is designed to investigate the safety and pharmacological properties of a short synthetic peptide mimic of Apolipoprotein A-I (apoA-I), referred to as the 5A peptide (or peptide 5A). This 5A peptide can potentially be used instead of recombinant apoA-I in Acute HDL Therapy and has several potential advantages over the use of recombinant apoA-I. When the 5A peptide is combined with sphingomyelin, the complex is referred to as the Fx-5A peptide-lipid complex. Fx-5A was specifically designed to remove excess cellular cholesterol via the ABCA1 transporter, which is thought to be one of the main anti-atherogenic functions of HDL. Furthermore, the peptide-lipid complex has been shown to mobilize macrophage cholesterol in animal models. Fx-5A markedly decreases the development of atherosclerotic plaque in preclinical models, such as in apoE-deficient mice, while also decreasing macrophage recruitment and foam cell formation in the rabbit collar model. Separately, animal models have shown that Fx-5A can also minimize inflammation associated with diseases like asthma, colitis and chronic kidney disease. The current research project is designed as a Phase 1A, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single intravenous infusion of the Fx-5A peptide-lipid complex at 4 different doses in healthy subjects. Each of the 4 dosing cohorts (2.5, 5.0, 10.0 and 20.0 mg/kg) will enroll 4 subjects. For each dosing cohort, there are three distinct phases of this study: Screening, Intervention, and Follow-Up.

Conditions

• Cardiovascular Disease

Interventions

Type	Name	Description
BIOLOGICAL	Fx-5A peptide complex	subject will receive a slow I.V. infusion of the Fx-5A peptide complex as described in Table 1. Five to 10 mL of blood will be collected at 30min (+/- 5min\*), 1h (+/- 10min\*), 2h (+/- 10min\*), 4h (+/- 15min\*), 8h (+/- 30min\*), 12h (+/- 30min\*), and 24h (+/- 30min\*) for laboratory tests and to be stored for research tests. The patient will be dismissed, as inpatient, 24-36 hours after the beginning of the treatment.

Timeline

• Start date: 2021-09-29
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2020-01-02
• Last updated: 2026-04-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study