A Study of Flurpiridaz (18F) Injection for PET Imaging for Assessment of MPI Quality Using HPLC and SPE Manufacturing Processes

• ClinicalTrials.gov Identifier: NCT04594941
• Recruitment Status: Not yet recruiting
• First Posted: October 20, 2020
• Last Update Posted: October 20, 2020
• Sponsor: GE Healthcare
• Information provided by (Responsible Party): GE Healthcare

Tracking Information

• First Submitted Date: September 29, 2020
• First Posted Date: October 20, 2020
• Last Update Posted Date: October 20, 2020
• Estimated Study Start Date: October 15, 2020
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 14, 2020)

Assess difference and variability between 2 sets of visually-based global rest scores resulting from 2 at-rest MPI sessions using Flurpiridaz (18F) Injection doses synthesized by the same or 2 different manufacturing processes [ Time Frame: 30 days ]

Intra-reader correlation and difference between the summed perfusion rest scores (SRS) and summed rest percent (SR%) after 2 MPI sessions using 2 Flurpiridaz (18F) Injection doses synthesized using the same or 2 different manufacturing processes

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 14, 2020)

• Assess the intra-reader agreement of the detection of ischemic defect on PET-MPI at rest between 2 MPI acquisitions using 2 Flurpiridaz (18F) Injection doses [ Time Frame: 30 days ]
  Variability of the SRS after MPI sessions using 2 Flurpiridaz (18F) Injection doses synthesized for the subjects receiving 2 doses of the product manufactured by the SPE process.
• Assess the intra-reader agreement of the detection of ischemic defect on PET-MPI at rest between 2 MPI acquisitions using 2 Flurpiridaz (18F) Injection doses [ Time Frame: 30 days ]
  Variability of the SRS after MPI sessions using 2 Flurpiridaz (18F) Injection doses synthesized for the subjects receiving 2 doses of the product manufactured by the HPLC process.
• Assess the intra-reader agreement of the detection of ischemic defect on PET-MPI at rest between 2 MPI acquisitions using 2 Flurpiridaz (18F) Injection doses [ Time Frame: 30 days ]
  Intra-reader agreement of the image quality score between the 2 sets of PET images acquired after two [18F]flurpiridaz injections using doses of Flurpiridaz (18F) Injection.
• Assess the detection of myocardial segmental defect similarity from 2 sets of images acquired from doses synthesized by the same or 2 different manufacturing processes of Flurpiridaz (18F) Injection PET for MPI at rest [ Time Frame: 30 days ]
  Difference between the perfusion rest scores for each of the 17 segments and each reader using 2 Flurpiridaz (18F) Injection doses synthesized using the same or 2 different manufacturing processes.
• Assess the equivalence of 2 sets of [18F]flurpiridaz time-activity curves (TACs) (blood, myocardium, lungs, liver) resulting from MPI using Flurpiridaz (18F) Injection doses synthesized by the same or 2 different manufacturing processes [ Time Frame: 30 days ]
  Difference in the standard uptake value (SUV) TACs and the relative difference in SUV (5- to 15-minute perfusion image) in left ventricular cavity, myocardium, lungs and liver measured after two [18F]flurpiridaz injections using doses of Flurpiridaz (18F) Injection synthesized by 2 different manufacturing processes.
• Assess the equivalence of 2 sets of [18F]flurpiridaz time-activity curves (TACs) (blood, myocardium, lungs, liver) resulting from MPI using Flurpiridaz (18F) Injection doses synthesized by the same or 2 different manufacturing processes [ Time Frame: 30 days ]
  Difference in the SUV TACs and the relative difference in SUV (5- to 15-minute perfusion image) in left ventricular cavity, myocardium, lungs and liver measured after two [18F]flurpiridaz injections using doses of Flurpiridaz (18F) Injection for the subjects receiving 2 doses of the product manufactured by the HPLC process.
• Assess the equivalence of 2 sets of [18F]flurpiridaz time-activity curves (TACs) (blood, myocardium, lungs, liver) resulting from MPI using Flurpiridaz (18F) Injection doses synthesized by the same or 2 different manufacturing processes [ Time Frame: 30 days ]
  Difference in the SUV TACs and the relative difference in SUV (5- to 15-minute perfusion image) in left ventricular cavity, myocardium, lungs and liver measured after two [18F]flurpiridaz injections using doses of Flurpiridaz (18F) Injection for the subjects receiving 2 doses of the product manufactured by the SPE process.
• Assess the safety of Flurpiridaz (18F) Injection PET doses synthesized by 2 different manufacturing processes [ Time Frame: 30 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Flurpiridaz (18F) Injection for PET Imaging for Assessment of MPI Quality Using HPLC and SPE Manufacturing Processes
• Official Title: A Descriptive, Comparative, Randomized, Crossover Study of Flurpiridaz (18F) Injection for Positron Emission Tomography (PET) Imaging for Assessment of Myocardial Perfusion Imaging Quality Using High Performance Liquid Chromatography (HPLC) and Solid Phase Extraction (SPE) Manufacturing Processes
• Brief Summary: This is a Phase 2 prospective, randomized, crossover study of Flurpiridaz (18F) Injection for PET-MPI in subjects referred for evaluation of known coronary artery disease (CAD) or for suspected CAD with intermediate to high pre-test probability (PTP). The objective is to assess the difference and variability between 2 sets of rest images synthesized by the same or 2 different manufacturing processes. Twenty-eight evaluable subjects will be enrolled in this study and will undergo 2 Flurpiridaz (18F) Injection PET-MPI at rest. Each subject will attend a Screening Visit at least 2 days and up to 14 days prior to the first Flurpiridaz (18F) Injection PET-MPI. The subjects will be randomized 1:1:1:1 to 4 possible sequences of receiving 2 doses of Flurpiridaz (18F) Injection: 2 groups of 7 subjects will receive 2 Flurpiridaz (18F) Injection doses synthesized by the same manufacturing processes (either HPLC or SPE) and 2 groups of 7 subjects will receive 2 Flurpiridaz (18F) Injection doses synthesized by different manufacturing processes (1 dose by HPLC followed by 1 dose by SPE or 1 dose by SPE followed by 1 dose by HPLC). All subjects will be followed up by telephone for adverse events (AEs) and serious AEs (SAEs) at 24 (+8) hours following each Flurpiridaz (18F) Injection administration.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Diagnostic

Condition

• Coronary Artery Disease (CAD)
• Ischemic Heart Disease

Intervention

Drug: Flurpiridaz (18F) Injection

All subjects will receive 2 IV boluses of Flurpiridaz (18F) Injection obtained either by the same manufacturing process (both HPLC or both SPE) or by 2 different manufacturing processes (1 HPLC and 1 SPE), in a large peripheral vein at rest. The subjects will be randomized 1:1:1:1 to 4 possible sequences of receiving 2 Flurpiridaz (18F) Injection. Seven subjects will receive 2 doses manufactured with the same HPLC process, 7 subjects will receive 2 doses manufactured with the same SPE process, and 2 groups of 7 subjects will receive 2 Flurpiridaz (18F) Injection doses synthesized by different manufacturing processes (1 dose by HPLC followed by 1 dose by SPE or 1 dose by SPE followed by 1 dose by HPLC).

Study Arms

• Experimental: Group 1
  7 evaluable subjects to receive 2 doses of Flurpiridaz (18F) Injection manufactured by the HPLC method
  Intervention: Drug: Flurpiridaz (18F) Injection
• Experimental: Group 2
  7 evaluable subjects to receive 2 doses of Flurpiridaz (18F) Injection manufactured by the SPE method
  Intervention: Drug: Flurpiridaz (18F) Injection
• Experimental: Group 3
  7 evaluable subjects to receive 1 dose of Flurpiridaz (18F) Injection manufactured by the HPLC method followed by 1 dose of Flurpiridaz (18F) Injection manufactured by the SPE method
  Intervention: Drug: Flurpiridaz (18F) Injection
• Experimental: Group 4
  7 evaluable subjects to receive 1 dose of Flurpiridaz (18F) Injection manufactured by the SPE method followed by 1 dose of Flurpiridaz (18F) Injection manufactured by the HPLC method
  Intervention: Drug: Flurpiridaz (18F) Injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: October 14, 2020): 34
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2020
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• * The subject is a man or woman ≥18 years of age

  • The subject is undergoing evaluation of known CAD or for suspected CAD with an intermediate to high PTP.
  • The subject has read, signed, and dated an informed consent form (ICF) prior to any study procedures being performed, and is willing to allow the study investigator to make the subject's medical records available to GE Healthcare.
  • The subject is male or is a nonpregnant, nonlactating female who is either surgically sterile (has a documented bilateral tubal ligation and oophorectomy and/or documented hysterectomy [bilateral tubal ligation alone is insufficient]) or is post-menopausal (cessation of menses for more than 1 year); enrollment in the study without a pregnancy test at Screening is allowed for these categories of female subjects. For women of childbearing potential, the results of either a urine or serum human chorionic gonadotropin pregnancy test (with the result known on the day of each radiopharmaceutical administration) must be negative. These subjects must be practicing appropriate birth control from the time of the screening to 30 days after the second radiopharmaceutical administration. Such methods include: hormonal contraception including oral contraceptives; intrauterine device; intrauterine hormone releasing system; bilateral tubal occlusion; vasectomized partner; sexual abstinence; adequate barrier method with spermicide (e.g., diaphragm, condom).
  • The subject is able and willing to comply with all study procedures as described in the protocol.

Exclusion Criteria:

• * Subjects who are pregnant, may possibly be pregnant, or wish (including their partners) to become pregnant during the study period, or are lactating

  • Subjects who are unable to undergo all of the imaging procedures

  • Subjects with unstable cardiovascular condition, including but not limited to:

    1. Transient ischemic attack/stroke within 3 months of enrollment;
    2. Significant congenital heart disease;
    3. Uncontrolled hypertension;
    4. Uncontrolled tachyarrhythmia leading to symptoms or hemodynamic compromise.
  • Subjects requiring cardiac intervention (i.e., percutaneous coronary intervention or coronary artery bypass graft) before completing the study.
  • Primary hemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant.

  • Subjects with screening laboratory findings as follows:

    1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal;
    2. Total bilirubin ≥2.0 mg/dL (34.2 μmol/L);
    3. Serum creatinine ≥3.0 mg/dL (265.2 μmol/L).
  • Subjects who present with any clinically active, serious, life-threatening disease, medical or psychiatric condition, and/or who have a life expectancy of <6 months, or for whom study participation may compromise their management; and subjects whom the investigator judges to be unsuitable for participation in the study for any reason.
  • Subjects undergoing evaluation for heart transplantation or with a history of heart transplantation.
  • Subjects enrolled in another clinical study within the 30 days before enrollment in this study.
  • Subjects previously enrolled in this study or any Flurpiridaz (18F) Injection study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Aleksandar Sarac; +44 (0) 7787 270 808; Aleksandar.sarac@ge.com

Contact: Emily Vandenbroucke, PhD; Emily.vandenbroucke@ge.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04594941
• Other Study ID Numbers: GE-265-001
• Has Data Monitoring Committee: No

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: Not Provided
• Responsible Party: GE Healthcare
• Study Sponsor: GE Healthcare
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: GE Healthcare
• Verification Date: October 2020