Gadopiclenol Pharmacokinetics, Safety and Efficacy in Children < 2 Years of Age

Study Overview
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Brief Summary
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This Phase II open-label, uncontrolled, multicenter trial is designed to investigate the pharmacokinetic (PK) profile of gadopiclenol in plasma, in pediatric patients aged up to 23 months inclusive (term neonates or preterm infants after the neonatal period), using a population PK approach. Primary objective is to evaluate the PK profile of gadopiclenol in plasma following single intravenous injection of 0.05 mmol/kg body weight (BW) in pediatric population aged up to 23 months (inclusive) scheduled for a contrast-enhanced MRI examination of any body region including central nervous system (CNS).

Detailed Description
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Inclusion will be performed using an age-down staggered approach. Three age groups will be defined: Group 1: patients aged 3 to 23 months (inclusive) Group 2: patients aged 28 days to less than 3 months; Group 3: patients aged from birth to 27 days (term newborns). The inclusions will start with the oldest patients (Group 1) and end with the youngest patients (Group 3). A total of 3 blood samples per patient will be taken post-injection for PK analysis.

Official Title
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Gadopiclenol Pharmacokinetics, Safety and Efficacy in Pediatric Patients < 2 Years of Age

Conditions
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Central Nervous System Diseases, Pediatric Disorder, Body Indication

Intervention / Treatment
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* Drug: Gadopiclenol


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Female or male pediatric patient aged from birth to 23 months of age inclusive (term neonates for all age groups or preterm infants after the neonatal period for groups 1 or 2). The neonatal period for preterm newborns is defined as the day of birth through the expected date of delivery plus 27 days. Term is defined as ≥37 completed weeks of amenorrhea, Patient with known or highly suspected abnormalities/ lesion(s) as detected by previous imaging examinations (including the fetal imaging, scheduled to undergo contrast-enhanced MRI of any body region including CNS [...] Main Exclusion Criteria: Patient planned for treatment or procedure (e.g. surgery) that would prevent from obtaining the required blood samples or performing other trial procedures between the screening visit and up to one 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 pharmacokinetic parameters, Patient with acute or chronic renal insufficiency defined as estimated Glomerular Filtration Rate (eGFR) out of age-adjusted normal value calculated based on bedside Schwartz equation, [...] 9. Patient undergoing a change in chemotherapy (product or dosage) within one day prior to or one day after gadopiclenol administration, 10. Patient who received or will receive any other contrast agent for CT and/or MRI within one week prior to or one week after gadopiclenol administration, 11. Patient with contraindication for MRI such as iron metal implants (e.g., aneurysm clips, pacemaker), 12. Patient with history of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents [...]

Ages Eligible for Study
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Maximum Age: 23 Months

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Age Group 1: patients aged 3 to 23 months<br>One Investigational Medicinal Product (IMP) dose of 0.05 mmol/kg will be injected in all patients. | Drug: Gadopiclenol<br>* Patients will receive a single dose of gadopiclenol calculated according to their BW on the day of MRI examination. Gadopiclenol will be administered at a dose of 0.05 mmol/kg BW (0.1 mL/kg BW).<br>* Other names: Elucirem;|
| Experimental: Age Group 2: patients aged 28 days to less than 3 months<br>One Investigational Medicinal Product (IMP) dose of 0.05 mmol/kg will be injected in all patients. | Drug: Gadopiclenol<br>* Patients will receive a single dose of gadopiclenol calculated according to their BW on the day of MRI examination. Gadopiclenol will be administered at a dose of 0.05 mmol/kg BW (0.1 mL/kg BW).<br>* Other names: Elucirem;|
| Experimental: Age Group 3: patients aged from birth to 27 days (term newborns)<br>One Investigational Medicinal Product (IMP) dose of 0.05 mmol/kg will be injected in all patients. | Drug: Gadopiclenol<br>* Patients will receive a single dose of gadopiclenol calculated according to their BW on the day of MRI examination. Gadopiclenol will be administered at a dose of 0.05 mmol/kg BW (0.1 mL/kg BW).<br>* Other names: Elucirem;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simulated concentrations at 10 minutes post injection | Determined from population PK | Concentration is simulated at 10 minutes post injection | 
| Simulated concentrations at 20 minutes post injection | Determined from population PK | Concentration is simulated at 20 minutes post injection | 
| Simulated concentrations at 30 minutes post injection | Determined from population PK | Concentration is simulated at 30 minutes post injection | 
| Area Under the Curve | Determined from population PK | A total of 3 blood samples per patient will be taken post-injection for PK analysis, one within each window (10-60 minutes, 2-4 hours and 6-8 hours). | 
| Elimination half-life | Determined from population PK | A total of 3 blood samples per patient will be taken post-injection for PK analysis, one within each window (10-60 minutes, 2-4 hours and 6-8 hours). | 
| Total clearance | Determined from population PK | A total of 3 blood samples per patient will be taken post-injection for PK analysis, one within each window (10-60 minutes, 2-4 hours and 6-8 hours). | 
| Volume of distribution | Determined from population PK | A total of 3 blood samples per patient will be taken post-injection for PK analysis, one within each window (10-60 minutes, 2-4 hours and 6-8 hours). |