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

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ClinicalTrials.gov Identifier: NCT04216342
Recruitment Status : Recruiting
First Posted : January 2, 2020
Last Update Posted : July 29, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief 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.


Condition or disease Intervention/treatment Phase
Cardiovascular Disease Biological: Fx-5A peptide complex Phase 1

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 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 a 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Intravenous, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers
Estimated Study Start Date : August 3, 2021
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : June 30, 2022

Arm Intervention/treatment
Experimental: 1
subjects entered into the trial may go thru a 0-4 weeks screening (Screening Phase). On the Intervention phase, subjects will be followed for 7 days which includes: entry criteria assessments and settling at the inpatient unit on Day 0, a single-dose I.V. infusion with data collection on Day 1 followed by 24 hours monitoring (Day 2), a 7-day and 28-day outpatient follow-up visit (Follow-Up Phase).
Biological: Fx-5A peptide complex
subject will receive a slow I.V. infusion of the Fx-5A peptide complex. 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 goal will be to collect the samples at the exact time, but a delay within the +/- specified time will not be considered a deviation). The patient will be dismissed, as inpatient, 24-36 hours after the beginning of the treatment.




Primary Outcome Measures :
  1. Assess the safety and tolerability of the Fx-5A peptide complex. [ Time Frame: 28 days ]
    A 'complete study' is defined by the procedures described up to day 7 after Fx-5A infusion, the intervention phase of the study. A 28 days follow up is designed to study the immunogenicity of the drug. Once a subject completes the day 28 follow up the study is ended for the subject ('end of the study').



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:
  • 18 years of age or above
  • Women of childbearing potential must be willing to use an appropriate form of birth control during the course of the study and two forms of birth control during the interventional portion of the study and up to day 7 after infusion
  • Subject willing to return for all study visits, complete all study-related tasks, and agree not to participate in other research studies from screening visit to study completion
  • Willingness and capacity to provide written informed consent

EXCLUSION CRITERIA:

  • Pregnancy, planned pregnancy (within the study period), or current breastfeeding
  • Subject taking any supplements or medications for at least 8 weeks prior to enrollment (with the exception of oral contraceptives).
  • Known allergies or intolerances to any components of the Fx-5A peptide-lipid complex
  • Known allergies or intolerances to eggs or egg components
  • History of febrile illness within 5 days prior to dosing
  • Hypertension (not treated or uncontrolled&)
  • BMI equal to or above 30 kg/m^2, and weight above 247 lb (112.3 kg).
  • Blood donation equal to or above 500 mL within 2 months prior to dosing.
  • Treatment with an investigational drug within a month or 5 half-lives of the investigational drug, whichever is longer, prior to dosing.
  • Laboratory changes (with CTCAE grade 2 or above): Abnormal levels of ALT, AST, CK, CRP, Alkaline Phosphatase, HbA1c, Urea, Creatinine, TSH, hemoglobin and hematocrit.
  • Subjects with renal (eGFR<90 mL/min /1.73m^2) or liver impairment
  • Subjects may also be excluded for any reason that may compromise their safety or the accuracy of research data collection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04216342


Contacts
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Contact: Katherine C Roskom, R.N. (301) 451-7094 katherine.roskom@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Marcelo J Amar, M.D. National Heart, Lung, and Blood Institute (NHLBI)
Additional Information:
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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT04216342    
Other Study ID Numbers: 200029
20-H-0029
First Posted: January 2, 2020    Key Record Dates
Last Update Posted: July 29, 2021
Last Verified: September 24, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Pharmacology
PEPTIDE
ApoA-I
Fx-5A
Additional relevant MeSH terms:
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Cardiovascular Diseases