A Study of XTR004 Radiotracer in Healthy Volunteers

Phase 1

Completed

• Conditions: Coronary Artery Disease (CAD); Myocardial Ischemia
• Interventions: Diagnostic Test: XTR004

• Registration Number: NCT05195879
• Lead Sponsor: Sinotau Pharmaceutical Group

Brief Summary

XTR004 is a 18F-labeled myocardial perfusion positron emission tomography tracer use to measure myocardial perfusion and myocardial blood flow. XTR004 binds to the myocytes and targets respiratory chain complex 1 in the mitochondria.This phase I study investigated the safety, biodistribution, radiation dosimetry and Pharmacokinetics of XTR004 in 10 healthy Chinese adults volunteers.

Detailed Description

XTR004 is a 18F-labeled myocardial perfusion PET tracer, the first one developed in China by Sinotau Pharmaceutical Group. XTR004 targets and binds to the mitochondrial complex I protein. XTR004 reflects myocardial function at a molecular level. In pre-clinical studies XTR004 demonstrated high myocardial first-pass extraction and prolonged retention, allowing for early or delayed imaging. XTR004 can be clinically used to measure myocardial perfusion and myocardial blood flow. This Phase I study will be open-labeled, nonrandomized, single center study. Enrolled 10 healthy Chinese adults who meet all of the inclusion and none of the exclusion criteria. Subjects will receive 6-8 mCi of XTR004 via IV injection. Safety and tolerability will be observed. Biodistribution, pharmacokinetics, and dosimetry will be investigated.

Study Timeline

• Study Start: 2021-03-23
• Study First Submitted: 2021-07-22
• Primary Completion: 2021-07-30
• Study Completion: 2021-07-30
• Status Verified: 2022-01
• Study First Submitted QC: 2022-01-13
• Study First Posted: 2022-01-19
• Last Update Submitted: 2022-01-23
• Last Update Posted: 2022-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Chinese men and women are included age between 18-40 years
2. Normal vital signs and physical examination
3. No clinical abnormalities in ECG, EEG, and echocardiogram
4. No past history of cardiovascular, cerebrovascular, or gastrointestinal diseases
5. Normal or no clinical significance abnormalities in laboratory tests
6. No any other major or chronic illness
7. No presence of drug use
8. Females adopt effective medically approved contraceptive methods to prevent pregnancy for at least 6 months before the study and after the study
9. Voluntarily agree and signed written consent

Exclusion Criteria

1. Previous history of cardiovascular diseases
2. A history of or physical or radiographic manifestations of any previous brain disease
3. Any previous major disease or unstable condition
4. Subjects who cannot complete XTR004 imaging as required
5. Positive HIV, hepatitis C or Treponema pallidum antibody and hepatitis B surface antigen detection
6. A history of coagulation or coagulation disorder
7. A history of liver or gastrointestinal disease or other conditions that interfere with drug absorption, distribution, excretion or metabolism as determined by the investigator
8. Previous history of cancer
9. High risk of drug allergic reaction
10. A history of alcohol or drug abuse/dependence
11. Exposure to significant occupational radiation (e.g >50 mvs/year) or exposure to radioactive substances for therapeutic or research purposes over the past 10 years
12. Scheduled surgery or other invasive interventions within one week before drug injection
13. Subjects use any drug or treatment that may interfere with the experimental data or cause serious side effects, as determined by the investigator
14. Pregnant or lactating women
15. Admitted to hospital due to illness during screening period Other conditions that investigators consider inappropriate to participate in a trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
XTR004	XTR004	Single dose 6.0-8.0 mCi intravenous injection of XTR004 and investigation of XTR004 (MPI radiotracer).

Primary Outcome Measures

Name	Time	Method
Changes in Laboratory tests	up to 14 days post injection	Safety observation: Measurements of routine blood (g/L), routine urine (mg/dL), and blood troponin-I levels (ng/ml) after drug injection. To observe and report changes in routine blood, routine urine, and blood troponin-I levels compared to baseline values obtained before drug injection.
Physical examination of the major organ systems	up to 14 days post injection	Safety observation: Observation of Cardiovascular system (blood pressure, pulse rate, and rhythm), Lungs (respiratory rate, chest expansion, and lung auscultation), Abdominal system (for any tenderness or organ enlargement), Nervous system ( cognitive testing, motor strength and control, including mental status), Musculoskeletal system, and Skin for any abnormalities, after drug injection. To report number of participants with changes in physical examination compared to baseline physical examination obtained before drug injection.
Monitoring of body temperature	up to 14 days post injection	Safety observation: Vital sign monitoring of body temperature (degrees celsius ) after drug injection. To report changes in body temperature compared to baseline body temperature obtained before drug injection.
12-lead Electrocardiography	up to 14 days post injection	Safety observation: Observation of ECG electrical activity pattern in the P-wave, PR interval, QRS wave complex, ST segment, and T-wave if associated with any abnormality after drug injection. To observe and report participants with ECG abnormality compared to baseline ECG obtained before drug injection.
Monitoring of respiratory rate	up to 14 days post injection	Safety Observation: Vital sign monitoring of respiratory rate (breath per minute) after drug injection. To report changes in respiratory rate compared to baseline respiratory rate obtained before drug injection.
Monitoring of pulse rate	up to 14 days post injection	Safety Observation: Vital sign monitoring of pulse rate (beats per minute) after drug injection. To report changes in pulse rate compared to baseline pulse rate obtained before drug injection.
Monitoring of Blood pressure	up to 14 days post injection	Safety Observation: Vital sign monitoring of blood pressure (mmHg) after drug injection. To report changes in blood pressure compared to baseline blood pressure obtained before drug injection.
Incidence of adverse events	up to 14 days post injection	Safety Observation: Number of participants with adverse events and severe adverse events after drug injection.

Secondary Outcome Measures

Name	Time	Method
Urine radioactivity analysis	up to 7.25 hours	Urine will be collected up to \~ 7.25 hours to assess for radioactivity, post injection.
Biodistribution of XTR004 after a single dose IV injection. PET scan acquisition;	up to 4.5 hours	Whole-body PET scan obtained at the following time points; at 0-60, 120, 150, 240, and 270 minutes, post injection.
Plasma and blood radioactivity analysis	up to 7 hours	Venous blood collection of 6ml at 1.5, 3, 5, 10, 30, 60, 120, 240 and 420 minutes for plasma and blood radioactivity analysis, post injection

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China