Diagnostic Validity of [18F]GP1 PET for Diagnosing Acute Deep Vein Thrombosis

Study Overview
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Brief Summary
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The first-in-human study of [18F]GP1 positron emission tomography/computed tomography (PET/CT) showed that [18F]GP1 is safe and promising novel PET tracer for imaging acute venous thromboembolism with favorable biodistribution and pharmacokinetics in patients. The goal of this phase 2 study is to evaluate whether [18F]GP1 PET/CT is sensitive and specific for the diagnosis of acute deep vein thrombosis in the appropriate patient population and clinical setting. This study will provide preliminary evidence of efficacy and expand the safety database in a larger group of patients who were suspected of having acute deep vein thrombosis. This study will further optimize image acquisition techniques, and develop methods and criteria by which [18F]GP1 PET/CT will be evaluated. Other critical questions about [18F]GP1 biodistribution including [18F]GP1 uptake in pulmonary and systemic arteries will be evaluated.

Detailed Description
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This study is an open label, non-randomized, single center, intervention study. An estimated 63 symptomatic subjects with a pretest score of deep vein thrombosis likely (Wells score ≥ 2) or a positive D-dimer test will receive [18F]GP1 PET/CT to evaluate the diagnostic validity of [18F]GP1 PET/CT for detecting deep vein thrombosis foci in lower extremities. The study comprises 3 periods: screening, treatment, and follow-up. The screening period starts with the patient's signature on the informed consent form and ends with assignment to treatment that is inclusion of the subject for treatment. The treatment period starts with baseline measurements, and ends with the last measurement/procedure on the day of intravenous injection of 250 MBq of [18F]GP1. The follow-up period contains the end-of-study interview. Key measurement is the PET/CT image acquisition about 120 minutes after the single injection of [18F]GP1 This study includes venous ultrasonography of deep vein thrombosis as a valid reference standard. [18F]GP1 PET/CT will be assessed qualitatively and quantitatively by three experienced readers. This study will be monitored regularly by a clinical research associate from the sponsor or a designated contract research organization. Data quality and study integrity will be assessed. The investigator will document the items that are required to evaluate the study in the subject files. Data required according to this protocol are to be recorded on the case report forms provided by the sponsor as soon as possible.

Official Title
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A Phase 2, Open-label, Non-randomized, Single Center Study to Assess Diagnostic Validity of [18F]GP1 Positron Emission Tomography/Computed Tomography for Acute Deep Vein Thrombosis of the Lower Extremities in Symptomatic Patients

Conditions
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Venous Thrombosis

Intervention / Treatment
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* Drug: [18F]GP1 positron emission tomography/computed tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A subject will be enrolled if he/she meets all of the following inclusion criteria. Subject is aged between 19 and 79 years and male or female of any race/ethnicity. Patient has a first episode of clinically suspected acute deep vein thrombosis of the lower extremity within 14 days prior to the planned [18F]GP1 PET/CT. The pretest probability for deep vein thrombosis is likely by two-level Wells score (≥ 2), or the D-dimer test is positive. Subject underwent or is scheduled to undergo venous ultrasonography within 7 days of [18F]GP1 PET/CT: Patient has Eastern Cooperative Oncology Group performance status of 0-2 at time of screening. Exclusion Criteria: A subject is to be excluded from the study if he/she does not fulfill the inclusion criteria or display any of the following criteria. Subject or subject's legally acceptable representative does not provide written informed consent. Subject has a previous history of objectively diagnosed deep vein thrombosis or pulmonary embolism. Subject has symptoms of acute deep vein thrombosis lasting for longer than 4 weeks at time of screening. Subject is suspected to have pulmonary embolism with shock or hypotension Subject had pretreatment with glycoprotein IIb/IIIa inhibitors within 15 days before the administration of [18F]GP1. Anticancer chemotherapy is scheduled to be given to subject before or within 24 hours after administration of [18F]GP1. Female subject is pregnant or nursing. Exclusion of the possibility of pregnancy is made by one of the following: 1) woman is physiologically post-menopausal (cessation of menses for more than 2 years), or 2) woman is surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy). If the woman is of childbearing potential, a urine pregnancy test performed within 24 hours immediately prior to administration of [18F]GP1 has to be negative and the women is advised to apply contraceptive measures during her participation in this study. Subject has concurrent severe and/or uncontrolled and/or unstable medical disease other than cancer (e.g. congestive heart failure, acute myocardial infarction, severe pulmonary disease, chronic renal or hepatic disease) which could compromise participation in the study in the judgment of the investigator. Subject is a relative of the investigator, student of the investigator or otherwise dependent. Subject has been involved in another investigative clinical study involving administration of an investigational drug from preceding 4 weeks prior to the study enrollment or within 24 hours after administration of [18F]GP1. Subject has been previously included in this study. Subject has any other condition or personal circumstances that, in the judgment of the investigator, might make collection of complete data difficult or impossible. Additive-related precautions: This investigational product contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Symptomatic subjects with a pretest score of deep vein thrombosis likely (Wells score ≥ 2) or a positive D-dimer test will receive [18F]GP1 PET/CT.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep vein thrombosis<br>Subjects with Deep vein thrombosis will receive a single IV injection of [18F] GP1 | Drug: [18F]GP1 positron emission tomography/computed tomography<br>* A radioactive dose of 250 MBq of the study drug with a total quantity of ≤ 10 µg will be administered as slow intravenous bolus injection over up to 60 seconds. PET/CT examinations will be performed at 120 ± 15 min after the administration of [18F]GP1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of qualitative [18F]GP1 PET/CT interpretation for the diagnosis of patients with acute proximal deep vein thrombosis | Sensitivity = (the number of [18F]GP1 PET/CT-positive patients divided by the number of ultrasonography-positive patients) x 100; specificity = (the number of [18F]GP1 PET/CT-negative patients divided by the number of ultrasonography-negative patients) x 100. | within 7 days of [18F]GP1 PET/CT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the receiver operating characteristic curve, sensitivity and specificity of quantitative [18F]GP1 PET/CT interpretation for the diagnosis of patients with acute proximal deep vein thrombosis | Area under the receiver operating characteristic curve. Sensitivity = (the number of [18F]GP1 PET/CT-positive patients divided by the number of ultrasonography-positive patients) x 100; specificity = (the number of [18F]GP1 PET/CT-negative patients divided by the number of ultrasonography-negative patients) x 100. | Within 7 days of [18F]GP1 PET/CT | 
| Positive and negative percent agreement between qualitative [18F]GP1 PET/CT and ultrasonography interpretation for the diagnosis of patients with acute distal deep vein thrombosis | Positive percent agreement = (the number of [18F]GP1 PET/CT-positive patients divided by the number of ultrasonography-positive patients) x 100; negative percent agreement = (the number of [18F]GP1 PET/CT-negative patients divided by the number of ultrasonography-negative patients) x 100 | Within 7 days of [18F]GP1 PET/CT | 
| Positive and negative percent agreement between quantitative [18F]GP1 PET/CT and ultrasonography interpretation for the diagnosis of patients with acute distal deep vein thrombosis | Positive percent agreement = (the number of [18F]GP1 PET/CT-positive patients divided by the number of ultrasonography-positive patients) x 100; negative percent agreement = (the number of [18F]GP1 PET/CT-negative patients divided by the number of ultrasonography-negative patients) x 100 | Within 7 days of [18F]GP1 PET/CT | 
| Intra- and inter-reader variability of qualitative [18F]GP1 PET/CT interpretation for the assessment of acute proximal and distal deep vein thrombosis | kappa statistic | Within 1 day of [18F]GP1 PET/CT | 
| Detection rate of pulmonary embolism with [18F]GP1 PET/CT | The number of [18F]GP1 PET/CT-positive patients divided by the number of ultrasonography-positive patients) x 100; negative percent agreement = (the number of all patients who underwent [18F]GP1 PET/CT | Within 1 day of [18F]GP1 PET/CT | 
| Percent fraction of unmetabolized [18F]GP1 in plasma | Percentage | Within 1 day of [18F]GP1 PET/CT | 
| Incidence of treatment emergent adverse events | Number of participants with treatment emergent adverse events graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) | From the administration of [18F]GP1 to one day after [18F]GP1 PET/CT | 
| Blood pressure | mmHg | Pre-treatment and three hours after the administration of [18F]GP1 | 
| Heart rate | beats/minute | Pre-treatment and three hours after the administration of [18F]GP1 | 
| Body temperature | Celsius | Pre-treatment and three hours after the administration of [18F]GP1 | 
| Physical examination | The limited physical examination will comprise: general appearance, skin, neck, lungs, heart, abdomen, and a limited neurological examination (mental status, motor strength and sensor perception). | Pre-treatment and three hours after the administration of [18F]GP1 | 
| Blood tests for safety | The clinical laboratory safety parameters to be assessed are as follows: glutamate pyruvate transaminase, glutamate-oxaloacetate transaminase, alkaline phosphatase, total bilirubin, creatinine, potassium, sodium, total protein, blood urea nitrogen, albumin. | Pre-treatment and three hours after the administration of [18F]GP1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positron-Emission Tomography, Ultrasonography, Platelet Activation, Data Accuracy