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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 : September 27, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Tracking Information
First Submitted Date  ICMJE December 31, 2019
First Posted Date  ICMJE January 2, 2020
Last Update Posted Date September 27, 2021
Estimated Study Start Date  ICMJE September 30, 2021
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 31, 2019)
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 ).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2021)
Assess the PK and PD of the Fx-5A peptide-lipid 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 ).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers
Official Title  ICMJE An Intravenous, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cardiovascular Disease
Intervention  ICMJE 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.
Study Arms  ICMJE 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).
Intervention: Biological: Fx-5A peptide complex
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 31, 2019)
64
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2023
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Joy Lynne V Freeman (301) 480-7632 joylynne.freeman@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04216342
Other Study ID Numbers  ICMJE 200029
20-H-0029
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
Study Sponsor  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marcelo J Amar, M.D. National Heart, Lung, and Blood Institute (NHLBI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date September 20, 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP