Pharmacokinetics, Safety and Efficacy of P03277 in Pediatric Patients Undergoing Central Nervous System Contrast-enhanced MRI

Study Overview
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Brief Summary
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This is a pharmacokinetics (PK), open-label, uncontrolled, multicenter phase II trial with age-staggered approach. The primary objective is to evaluate the PK profile of gadopiclenol in plasma following single IV injection of 0.05 mmol/kg body weight (BW) in pediatric population aged from 2 to 17 years undergoing CNS contrast-enhanced MRI (CNS cohort).

Detailed Description
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A population PK approach and an age-down staggered approach will be used. Patients will be recruited into 3 predefined age groups: 12-17, 7-11 and 2-6 years. The inclusions will start with the older group (Adolescents, 12-17 years), followed by Preadolescents (7-11 years) and finally Young Children (2-6 years of age).

Official Title
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Pharmacokinetics, Safety and Efficacy of a New Gadolinium-based Contrast Agent, P03277, in Pediatric Patients From 2 to 17 Years of Age Undergoing Central Nervous System Contrast-enhanced MRI

Conditions
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Body Indication, Central Nervous System Indication, Pediatric Patients

Intervention / Treatment
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* Drug: P03277


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be included in the study, the patient had to meet all the following criteria: Female or male pediatric patient aged 2 to 17 years, Patient with known or suspected lesion(s) scheduled to undergo routine contrast-enhanced MRI of CNS or of other organs including at least one organ among head and neck, thorax, abdomen, pelvis or musculoskeletal system (including extremities), Patient whose parent(s) or legal guardian having read the information, provided their consent to patient's participation in writing by dating and signing the informed consent prior to any trial related procedure being conducted, Patient with capacity of understanding who received age- and maturity-appropriate information and provided his/her assent to participate in the trial (as required by national regulations), Patient affiliated to national health insurance according to local regulatory requirements. Non-inclusion Criteria: Patients could not be included in the study if they presented with one or more of the following non-inclusion criteria: Patient planned for treatment or procedure (e.g., surgery) that would prevent obtaining the required blood samples or performing other trial procedures between the screening visit and up to 1 day after gadopiclenol administration, Patient undergoing treatment or procedure (e.g., diuretics, clinically significant blood loss or blood transfusion) preceding or subsequent to gadopiclenol administration that would alter gadopiclenol PK parameters, Patient with acute or chronic renal insufficiency defined as estimated Glomerular Filtration Rate (eGFR) out of age-adjusted normal ranges (eGFR calculated with bedside Schwartz equation), Patients referred for MR Angiography, Patient with history of bleeding disorder, Patient with known severe liver disease, Patient with known cardiac disease (e.g., heart rhythm anomalies, long QT syndrome), Patient with any clinically significant abnormal 12-lead ECG that in the Investigator's opinion would affect the safety evaluation or place the patient at risk, Patient with electrolyte or fluid imbalance that at Investigator's judgment presents undue risk assessed within 1 month prior to gadopiclenol administration, Patient undergoing a change in chemotherapy within 1 day prior to or 1 day after gadopiclenol administration, Patient who received any other contrast agent for CT and/or MRI within 1 week prior to or 1 week after gadopiclenol administration, Patient with contraindication for MRI such as iron metal implants (e.g., aneurysm clips, pacemaker), Patient with history of anaphylactoid or anaphylactic reaction to any allergen including drugs, Patient with history of hypersensitivity caused by any contrast media / agents (iodinated or gadolinium-based), Patient with known contraindication(s) to the use of any GBCA, Pregnant or breast-feeding female patient (female patient with childbearing potential [who experienced menarche] must have a negative urine pregnancy test within 24 hours prior to gadopiclenol administration and must be using medically approved contraception* if sexually active), Patient with anticipated, current or past condition (medical, psychological, social or geographical) that would compromise the patient's safety or her/his ability to participate to the whole trial, Patient unlikely to comply with the protocol, e.g., uncooperative attitude of parent(s) or legal guardian, inability to return for follow-up visits and unlikelihood of completing the trial, Having participated in a clinical trial and having received any investigational product within 7 days prior to gadopiclenol administration or planned during the trial, Patient previously included in this trial, Patient related to the Investigator or any other trial staff or relative directly involved in the trial conduct. medically approved contraception methods include: female sterilization, use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception, placement of an Intrauterine Device (IUD) or Intrauterine System (IUS), barrier methods of contraception (condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository).

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNS Cohort 2-6 years<br>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI | Drug: P03277<br>* A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.<br>* Other names: gadopiclenol;|
| Experimental: CNS Cohort 7-11 years<br>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI | Drug: P03277<br>* A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.<br>* Other names: gadopiclenol;|
| Experimental: CNS Cohort 12-17 years<br>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI | Drug: P03277<br>* A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.<br>* Other names: gadopiclenol;|
| Experimental: Body Cohort 2-6 years<br>Pediatric patients aged 2-6 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system) | Drug: P03277<br>* A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.<br>* Other names: gadopiclenol;|
| Experimental: Body Cohort 7-11 years<br>Pediatric patients aged 7-11 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system) | Drug: P03277<br>* A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.<br>* Other names: gadopiclenol;|
| Experimental: Body Cohort 12-17 years<br>Pediatric patients aged 12-17 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system) | Drug: P03277<br>* A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.<br>* Other names: gadopiclenol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elimination Half-life | P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort. | 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours | 
| Total Clearance | P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort. | 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours | 
| Central Volume of Distribution | P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort. | 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours | 
| Peripheral Volume of Distribution | P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort. | 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours | 
| Area Under the Curve | P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort. | 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours | 
| Simulated Concentrations 10 Minutes Post-injection | P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort. | 10 minutes post-injection | 
| Simulated Concentrations 20 Minutes Post-injection | P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort. | 20 minutes post-injection | 
| Simulated Concentrations 30 Minutes Post-injection | P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort. | 30 minutes post-injection |