RAdiolabeled Perfusion to Identify Coronary Artery Disease Using WAter To Evaluate Responses of Myocardial FLOW (RAPID-WATER-FLOW)

• ClinicalTrials.gov Identifier: NCT05134012
• Recruitment Status: Recruiting
• First Posted: November 24, 2021
• Last Update Posted: April 18, 2024
• Sponsor: MedTrace Pharma A/S
• Information provided by (Responsible Party): MedTrace Pharma A/S

Tracking Information

• First Submitted Date: October 29, 2021
• First Posted Date: November 24, 2021
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: May 8, 2022
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 29, 2023)

Sensitivity and specificity of the [15-O]-H2O PET study using the truth-standard of ICA with FFR/iFR or CCTA. [ Time Frame: 30 days ]

Sensitivity and specificity are defined as follows:

• True Positives (TP): Subjects with abnormal PET MPI and disease positive by the truth standard
• True Negatives (TN): Subjects with normal PET MPI and disease negative by the truth standard
• False Positives (FP): Subjects with abnormal PET MPI and disease negative by the truth standard
• False Negatives (FN): Subjects with normal PET MPI and disease positive by the truth standard
• Sensitivity: TP/(TP + FN)
• Specificity: TN/(TN + FP)

Original Primary Outcome Measures (submitted: November 15, 2021)

Sensitivity and specificity of the [15-O]-H2O PET study using the truth-standard of ICA with FFR or CCTA. [ Time Frame: 30 days ]

All efficacy assessments will be based on a blinded analysis of all imaging data. The primary efficacy endpoints of the study are the sensitivity and specificity defined as follows: Sensitivity = Number of participants with true-positive [15-O]-H2O assessments / Number of participants with CAD Specificity = Number of participants with true-negative [15-O]-H2O assessments / Number of participants with no CAD

Current Secondary Outcome Measures (submitted: June 10, 2022)

• Sensitivity, specificity, and accuracy of [15-O]-H2O PET MPI in participants of special clinical interest (female, BMI≥30, diabetics, multivessel disease). [ Time Frame: 30 days ]
  Sensitivity and specificity are defined as follows:

  • True Positives (TP): Subjects with abnormal PET MPI and disease positive by the truth standard
  • True Negatives (TN): Subjects with normal PET MPI and disease negative by the truth standard
  • False Positives (FP): Subjects with abnormal PET MPI and disease negative by the truth standard
  • False Negatives (FN): Subjects with normal PET MPI and disease positive by the truth standard
  • Sensitivity: TP/(TP + FN)
  • Specificity: TN/(TN + FP)
  • Accuracy: (TN + TP)/(TN + TP + FN + FP)
• Adverse event analyses will include tabulations of the incidence (number and percent of subjects) with at least one TEAEs overall and by MedDRA system organ class (SOC) and preferred term (PT). This will be repeated for serious adverse. [ Time Frame: 30 days ]
  Other Safety measures including the following will be summarized descriptively:

  1. ECG (ventricular heart rate, PR interval, QRS duration, QT interval, QTc interval)
  2. Vital Signs
  3. Concomitant Medications
  4. Protocol Deviations

Original Secondary Outcome Measures (submitted: November 15, 2021)

• Sensitivity and specificity of [15-O]-H2O PET MPI in participants of special clinical interest (female, BMI≥30, diabetics, multivessel disease) [ Time Frame: 30 days ]
  Subgroup analyses will be performed using the independent readers' assessments to determine the sensitivity, specificity, and accuracy of P3 MT-100 [15-O]-H2O PET in subjects of special clinical interest (female, BMI≥30, diabetics, MVD). The sensitivity and specificity are defined as follows: Sensitivity = Number of participants with true-positive [15-O]-H2O assessments / Number of participants with CAD Specificity = Number of participants with true-negative [15-O]-H2O assessments / Number of participants with no CAD
• Incidence (number and percent of participants) of treatment-emergent adverse events (TEAEs) and procedure-related AEs by MedDRA system organ class (SOC) and preferred term (PT). [ Time Frame: 30 days ]
  A TEAE is an event that started or worsened in severity at or after start of [15-O]-H2O injection. Such adverse events (AEs) and serious adverse events (SAEs) will be followed from the start time of [15-O]-H2O administration through 24 ± 8 hours after the start time of the second (stress) [15-O]-H2O administration. This analysis will be performed on the overall safety population.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: RAdiolabeled Perfusion to Identify Coronary Artery Disease Using WAter To Evaluate Responses of Myocardial FLOW (RAPID-WATER-FLOW)
• Official Title: A Phase 3, Multicenter, Open Label Study to Confirm the Diagnostic Potential of Intravenously Administered [15-O]-H2O to Identify Coronary Artery Disease During Pharmacological Stress and Resting Conditions Using PET Imaging (RAPID-WATER-FLOW)
• Brief Summary: This a Phase 3, prospective, open-label, multicenter study of [15-O]-H2O injection for PET imaging of subjects with suspected CAD. Approximately 182 evaluable participants with suspected CAD referred for testing will be included in the study at approximately 10 study sites in the United States and Europe. Approximately 215 participants will be enrolled to account for an estimated 15% drop-out rate. Screening assessments will occur prior to enrollment to confirm eligibility. All participants will receive two doses of [15-O]-H2O as part of a single PET imaging session (one dose at rest and one during pharmacological stress with adenosine). A safety follow-up phone call will occur 24 ± 8 hrs after completion of the [15-O]-H2O scan.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Approximately 182 evaluable participants with suspected CAD referred for testing will be included in the study. All participants will receive two doses of [15-O]-H2O as part of a single PET imaging session (one dose at rest and one during pharmacological stress with adenosine).

Masking: None (Open Label)
Primary Purpose: Diagnostic

• Condition: Coronary Artery Disease

Intervention

Drug: [O-15]-Water PET Myocardial Perfusion Imaging (MPI)

[15-O]-H2O injection is a novel PET imaging agent labeled with the radioisotope [15-O] administered as an intravenous (IV) injection. Participants will receive [15-O]-H2O treatment twice as a part of a single day imaging session. All participants will receive two IV boluses of [15-O]-H2O injection in a peripheral vein; one at rest and one during pharmacological stress.

Study Arms

Experimental: [O-15]-Water PET Myocardial Perfusion Imaging (MPI)

All participants with suspected CAD will receive two doses of [15-O]-H2O as part of a single PET imaging session (one dose at rest and one during pharmacological stress with adenosine).

Intervention: Drug: [O-15]-Water PET Myocardial Perfusion Imaging (MPI)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 15, 2021): 215
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2025
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male and female participants ≥18 years;
2. Informed consent form (ICF) read, signed, and dated prior to any study procedures being performed;

3. Participants who fall into any one of the following categories:

   1. Have been referred for an ICA directly of after non-invasive testing (e.g., SPECT or PET MPI, stress echo, CCTA, ETT).
   2. Had an ICA with no intervention. However, if any stenosis >40% but ≤70% was observed, an FFR or iFR assessment was performed.
   3. Had a CCTA with normal coronaries or minimal CAD (no stenosis >25%).

   The SPECT study, PET 15O-H2O study, and ICA or CCTA testing need to be completed within a 30-day window, with time 0 defined as the date of the first of these three tests.

4. Women of Child Bearing Potential (WOCBP) must be non-pregnant, and non-lactating. For women of childbearing potential, the results of a urine human chorionic gonadotropin (HCG) pregnancy test (with the result known on the day of drug administration) must be negative; these participants must be practicing appropriate birth control from time of the screening visit until the end of the follow-up period. For women who are either surgically sterile (have a documented bilateral tubal ligation or oophorectomy and/or hysterectomy) or are post-menopausal (cessation of menses for more than 1 year), enrollment in the study without a pregnancy test at screening is allowed.
5. Male will need to use contraceptive methods until end of the follow-up period.
6. Participants are able to comply with all study procedures as described in the protocol.

Exclusion Criteria:

1. Participants are unable to undergo (even partially) any of the imaging procedures;

2. Participants with a known history of cardiac disease including:

   1. myocardial infarction, previous coronary revascularization, or chronic ischemic cardiomyopathy
   2. primary myocardial disease such as cardiac amyloidosis or hypertrophic cardiomyopathy
   3. known left ventricular dysfunction
   4. moderate or severe aortic or mitral stenosis or regurgitation

3. Participants in whom adenosine stress testing is contraindicated, including but not limited to:

   1. Participants with severe COPD or chronic asthma.
   2. Participants with second- or third-degree atrioventricular block without a pacemaker.
4. Participants with claustrophobia to an extent that would limit their ability to undergo SPECT and PET imaging (patients whose claustrophobia is known to be readily controlled with drugs or psychological support may be enrolled).
5. Participants who are on sildenafil (Viagra) or oral dipyridamole (Persantine, Aggrenox) therapy or on any PDE5 inhibitor (i.e. tadalafil, avanafil, vardenafil),and for whom its use cannot be terminated or suspended for ≥24 hours prior to treatment of study drug.
6. Participants with significant co-morbidities that would prevent appropriate completion of the protocol procedures.
7. Participants who have participated in another research study using investigational drugs within the 30 days prior to enrollment or through the duration of the trial (patients in observational studies with approved agents and participants known to be on placebo may be enrolled).
8. Participants who have previously participated in this study.
9. Subjects scheduled for, or planning to undergo, any interventional cardiac procedures between enrollment and ICA (pathway 1) or signing of informed consent and 15O-H2O PET MPI (pathway 2 and 3)

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: Taylor A Williams; 16178024048 ext 162; twilliams@ccstrials.com

Contact: Michael DiBattista; mdibattista@ccstrials.com

• Listed Location Countries: Canada, Denmark, Sweden, United States

Administrative Information

• NCT Number: NCT05134012
• Other Study ID Numbers: MedTrace-002
• 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
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: MedTrace Pharma A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: MedTrace Pharma A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Emily Vandenbroucke, PhD; MedTrace Pharma A/S
• Principal Investigator: Marcelo DiCarli, MD; Brigham and Women's Hospital

• PRS Account: MedTrace Pharma A/S
• Verification Date: April 2024