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

NCT04594941 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GE-265-001
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 5

Brief Summary

This was a Phase 2 prospective, randomized, crossover study of Flurpiridaz (18F) Injection for PET-MPI in participants 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 \[participants were enrolled in this study and underwent 2 Flurpiridaz (18F) Injection PET-MPI at rest. Each participant attended a Screening Visit at least 2 days and up to 14 days prior to the first Flurpiridaz (18F) Injection PET-MPI. The participants were randomized 1:1:1:1 to 4 possible sequences of receiving 2 doses of Flurpiridaz (18F) Injection: 2 groups of 7 participants received 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 participants were followed up by telephone for adverse events (AEs) and serious AEs (SAEs) at 24 (+8) hours following each Flurpiridaz (18F) Injection administration.

Conditions

Coronary Artery Disease (CAD); Ischemic Heart Disease

Outcome Measures

Primary Outcomes (4)

• Intra-reader Difference of Summed Rest Score (SRS) for Positron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI)

  3 qualified readers (independent from the study) performed independent reads of all MPI images, inclusive of standard 17-segment polar-maps of perfusion defects. Each reader scored the perfusion pattern in each segment (17 segments) using a 5-point scale score range from 0 to 4: Normal 0, Minimal, mild impairment of perfusion = 1, Moderate impairment of perfusion = 2, Significant impairment of perfusion = 3, No perfusion = 4. Higher score indicated = impairment of perfusion. SRS was calculated by summing individual scores from each of 17 segments to give an overall score between 0 and 68; a score of 0 indicates normal outcome and scores more than 0 indicate increasingly worse outcomes as the score increases. The summed score of the 17 segments SRS was used for analysis. Intra-reader difference of SRS for PET MPI was reported.

  Up to 2 weeks

• Intra-reader Difference of Summed Rest Percent (SR%) for PET MPI

  3 qualified readers (independent from the study) performed independent reads of all MPI images, inclusive of standard 17-segment polar-maps of perfusion defects. Each reader scored the perfusion pattern in each segment (17 segments) using a 5-point scale score range from 0 to 4: Normal 0, Minimal, mild impairment of perfusion = 1, Moderate impairment of perfusion = 2, Significant impairment of perfusion = 3, No perfusion = 4. Higher score indicated = impairment of perfusion. SRS was calculated by summing individual scores from each of 17 segments to give an overall score between 0 and 68; a score of 0 indicates normal outcome and scores more than 0 indicate increasingly worse outcomes as the score increases. Summed score of the 17 segments SRS was used for analysis. SR% is calculated by dividing the SRS by a number corresponding to the SRS value indicating a deficit of 4 in every segment and then multiplying the result by 100. Intra-reader difference of SR% for PET MPI was reported.

  Up to 2 weeks

• Intra-reader Correlation of SRS for PET MPI: Pearson's Correlation

  3 qualified readers (independent from the study) performed independent reads of all MPI images, inclusive of standard 17-segment polar-maps of perfusion defects. Each reader scored the perfusion pattern in each segment (17 segments) using a 5-point scale score range from 0 to 4: Normal 0, Minimal, mild impairment of perfusion = 1, Moderate impairment of perfusion = 2, Significant impairment of perfusion = 3, No perfusion = 4. Higher score indicated = impairment of perfusion. SRS was calculated by summing individual scores from each of 17 segments to give an overall score between 0 and 68; a score of 0 indicates normal outcome and scores more than 0 indicate increasingly worse outcomes as the score increases. The summed score of the 17 segments SRS was used for analysis. Intra-reader correlation of SRS for PET MPI assessed using Pearson's correlation was reported.

  Up to 2 weeks

• Intra-reader Correlation of SRS for PET MPI: Kendall's Tau-b

  3 qualified readers (independent from the study) performed independent reads of all MPI images, inclusive of standard 17-segment polar-maps of perfusion defects. Each reader scored the perfusion pattern in each segment (17 segments) using a 5-point scale score range from 0 to 4: Normal 0, Minimal, mild impairment of perfusion = 1, Moderate impairment of perfusion = 2, Significant impairment of perfusion = 3, No perfusion = 4. Higher score indicated = impairment of perfusion. SRS was calculated by summing individual scores from each of 17 segments to give an overall score between 0 and 68; a score of 0 indicates normal outcome and scores more than 0 indicate increasingly worse outcomes as the score increases. The summed score of the 17 segments SRS was used for analysis. Intra-reader correlation of SRS for PET MPI assessed using Kendall's tau-b was reported.

  Up to 2 weeks

Secondary Outcomes (8)

• Variability of the SRS After MPI Sessions Using 2 Flurpiridaz (18F) Injection Doses by the Same Process

  Up to 2 weeks

• Percentage of Participants With Intra-Reader Agreement of the Detection of Ischemic Defect on PET-MPI at Rest Between 2 MPI Acquisitions Using 2 Flurpiridaz (18F) Injection Doses

  Up to 2 weeks

• Difference Between the Perfusion Rest Scores for Each of the 17 Segments and Each Reader for 2 Flurpiridaz (18F) Injection Doses From Same and Different Manufacturing Process

  Up to 2 weeks

• Difference in Standard Uptake Value (SUV) of Time-activity Curves (TACs) by Region After MPI Sessions Using 2 Flurpiridaz (18F) Injection Doses Synthesized by Same and 2 Different Manufacturing Processes

  Up to 2 weeks

• Relative Difference in SUV (5- to 15-minute Perfusion Image) of TACs by Region After MPI Sessions Using 2 Flurpiridaz (18F) Injection Doses Synthesized by Same and 2 Different Manufacturing Processes

  Up to 2 weeks

Study Arms (4)

Treatment Sequence: SPE-SPE

EXPERIMENTAL

Participants received 2 intravenous (IV) boluses of Flurpiridaz (18F) Injection manufactured by SPE process at Visit 1 and 2. The targeted dose to the body of Flurpiridaz (18F) Injection was to be in the range of 1.7 to 2.5 millicurie (mCi) (63 to 93 megabecquerel \[MBq\]) for each administration and not exceed a total of 6 mCi (222 MBq) for an individual participant.

Drug: Flurpiridaz (18F) Injection

Treatment Sequence: HPLC-HPLC

EXPERIMENTAL

Participants received 2 IV boluses of Flurpiridaz (18F) Injection manufactured by HPLC process at Visit 1 and 2. The targeted dose to the body of Flurpiridaz (18F) Injection was to be in the range of 1.7 to 2.5 mCi (63 to 93 MBq) for each administration and not exceed a total of 6 mCi (222 MBq) for an individual participant.

Drug: Flurpiridaz (18F) Injection

Treatment Sequence: SPE-HPLC

EXPERIMENTAL

Participants received 2 IV boluses of Flurpiridaz (18F) Injection manufactured by 2 different processes (1 dose manufactured by SPE followed by 1 dose manufactured by HPLC) at Visit 1 and 2. The targeted dose to the body of Flurpiridaz (18F) Injection was to be in the range of 1.7 to 2.5 mCi (63 to 93 MBq) for each administration and not exceed a total of 6 mCi (222 MBq) for an individual participant.

Drug: Flurpiridaz (18F) Injection

Treatment Sequence: HPLC-SPE

EXPERIMENTAL

Participants received 2 IV boluses of Flurpiridaz (18F) Injection manufactured by 2 different processes (1 dose manufactured by HPLC followed by 1 dose manufactured by SPE) at Visit 1 and 2. The targeted dose to the body of Flurpiridaz (18F) Injection was to be in the range of 1.7 to 2.5 mCi (63 to 93 MBq) for each administration and not exceed a total of 6 mCi (222 MBq) for an individual participant.

Drug: Flurpiridaz (18F) Injection

Interventions

Flurpiridaz (18F) Injection DRUG

All participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein at rest.

Treatment Sequence: HPLC-HPLC; Treatment Sequence: HPLC-SPE; Treatment Sequence: SPE-HPLC; Treatment Sequence: SPE-SPE

Eligibility Criteria

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

You may qualify if:

• \* The participant was a man or woman ≥18 years of age
• The participant was undergoing evaluation of known CAD or for suspected CAD with an intermediate to high PTP.
• The participant had read, signed, and dated an informed consent form (ICF) prior to any study procedures being performed, and was willing to allow the study investigator to make the participant's medical records available to GE Healthcare.
• The participant was male or was a nonpregnant, nonlactating female who was either surgically sterile (had a documented bilateral tubal ligation and oophorectomy and/or documented hysterectomy \[bilateral tubal ligation alone was insufficient\]) or was post-menopausal (cessation of menses for more than 1 year); enrollment in the study without a pregnancy test at Screening was allowed for these categories of female participants. 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 participants must have been practicing appropriate birth control from the time of the screening to 30 days after the second radiopharmaceutical administration. Such methods included: 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 participant was able and willing to comply with all study procedures as described in the protocol.

You may not qualify if:

• \* Participants who were pregnant, may possibly be pregnant, or wish (including their partners) to become pregnant during the study period, or were lactating
• Participants who were unable to undergo all of the imaging procedures
• Participant with unstable cardiovascular condition, including but not limited to:
• Transient ischemic attack/stroke within 3 months of enrollment;
• Significant congenital heart disease;
• Uncontrolled hypertension;
• Uncontrolled tachyarrhythmia led to symptoms or hemodynamic compromise.
• Participants required 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.
• Participants with screening laboratory findings as follows:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) was greater than 3 times the upper limit of normal;
• Total bilirubin ≥2.0 mg/dL (34.2 μmol/L);
• Serum creatinine ≥3.0 mg/dL (265.2 μmol/L).
• Participants who presented 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 participants whom the investigator judges to be unsuitable for participation in the study for any reason.
• Participants undergone evaluation for heart transplantation or with a history of heart transplantation.

Sponsors & Collaborators

• GE Healthcare: lead

Study Sites (5)

Indago Research and Health Center

Hialeah, Florida, 33012, United States

Location

Pioneer Clinical Studies

Miami, Florida, 33155, United States

Location

Amavita Clinical Research, LLC

North Miami Beach, Florida, 33169, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 39720, United States

Location

Memorial City and Katy Cardiology Associates

Katy, Texas, 77493, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease; Myocardial Ischemia

Interventions

Injections

Condition Hierarchy (Ancestors)

Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Francois Tranquart, M.D., Ph.D
• Organization: GE HealthCare

francois.tranquart@ge.com

447775543206

Study Officials

• Francois Tranquart, MD, PhD

  GE Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 20, 2020
• Study Start: January 27, 2022
• Primary Completion: May 26, 2022
• Study Completion: May 26, 2022
• Last Updated: August 1, 2023
• Results First Posted: August 1, 2023

Record last verified: 2023-07

Locations

US (5)