P03277 Dose Finding Study in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)

Study Overview
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Brief Summary
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The purpose of this study was to determine a safe and effective dose of a new gadolinium-based contrast agent (GBCA) P03277 based on the Contrast to Noise Ratio (CNR) when comparing with gadobenate dimeglumine (MultiHance®) at 0.1 mmol/kg body weight (BW). Contrast to Noise Ratio (CNR), a well-known quantitative parameter directly related to contrast medium/GBCA efficacy, was chosen as the primary endpoint in order to have a precise determination of P03277 clinical dose. This was a multi-center, international, prospective, double-blind, randomized, controlled, parallel dose groups, cross-over with comparator study in male and female subjects presenting with known or highly suspected focal areas of disruption of the Blood Brain Barrier including at least one expected enhancing lesion of minimum 5 mm, who were scheduled to undergo a routine contrast-enhanced Magnetic Resonance Imaging (MRI) of Central Nervous System.

Detailed Description
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Two subsets of subjects were included in the study: The subset 1 included the first randomized subject of each study center. Subjects were randomly assigned in a 1:1 ratio to receive 0.05 or 0.1 mmol/kg BW of P03277 and 0.1 mmol/kg BW of gadobenate dimeglumine. Subset 2 was composed of all subjects (except the first one of each study center) selected by the study center. Subjects were randomly assigned in a 1:1:1:1 ratio to receive 0.025, 0.05, 0.1 or 0.2 mmol/kg BW of P03277 and 0.1 mmol/kg BW of gadobenate dimeglumine. During the course of the study, two MRIs were obtained from each subject: one unenhanced and P03277-enhanced MRI; and one unenhanced and gadobenate dimeglumine-enhanced MRI. MRI images were evaluated off-site by 3 independent blinded readers for the primary endpoint (CNR).

Official Title
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P03277 Dose Finding Study in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)

Conditions
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CNS Lesion, Blood Brain Barrier Defect

Intervention / Treatment
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* Drug: P03277
* Drug: Gadobenate dimeglumine
* Device: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male adult subjects, with known or highly suspected focal areas of disrupted Blood Brain Barrier including at least one expected enhancing lesion of minimum 5 mm (long axis). This lesion had been detected on a previous imaging procedure (computerized Tomography [CT] or MRI). Subject scheduled for a routine contrast-enhanced MRI examination of Central Nervous System for clinical reasons and agreeing to have a second contrast-enhanced MRI examination for the purpose of the study. Exclusion Criteria: Subject presenting with acute or chronic Grade III (at least) renal insufficiency, defined as an estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m² based on one eGFR assessment performed the day of the MRI prior to the first contrast agent injection.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subset 1 Arm 1<br>One of the two doses of P03277 (0.05 or 0.1 mmol/kg)-enhanced MRI then gadobenate dimeglumine (0.1 mmol/kg)-enhanced MRI | Drug: P03277<br>* Single intravenous (IV) bolus injection at a rate of 2 mL/second<br>* Other names: Gadopiclenol;Drug: Gadobenate dimeglumine<br>* Single IV bolus injection at a rate of 2 mL/second<br>* Other names: MultiHance;Device: MRI<br> <br> |
| Experimental: Subset 1 Arm 2<br>Gadobenate dimeglumine (0.1 mmol/kg)-enhanced MRI then one of the two doses of P03277 (0.05 or 0.1 mmol/kg)-enhanced MRI | Drug: P03277<br>* Single intravenous (IV) bolus injection at a rate of 2 mL/second<br>* Other names: Gadopiclenol;Drug: Gadobenate dimeglumine<br>* Single IV bolus injection at a rate of 2 mL/second<br>* Other names: MultiHance;Device: MRI<br> <br> |
| Experimental: Subset 2 Arm 1<br>One of the four doses of P03277 (0.025, 0.05, 0.1 or 0.2 mmol/kg)-enhanced MRI then gadobenate dimeglumine (0.1 mmol/kg)-enhanced MRI | Drug: P03277<br>* Single intravenous (IV) bolus injection at a rate of 2 mL/second<br>* Other names: Gadopiclenol;Drug: Gadobenate dimeglumine<br>* Single IV bolus injection at a rate of 2 mL/second<br>* Other names: MultiHance;Device: MRI<br> <br> |
| Experimental: Subset 2 Arm 2<br>Gadobenate dimeglumine (0.1 mmol/kg)-enhanced MRI then one of the four doses of P03277 (0.025, 0.05, 0.1 or 0.2 mmol/kg)-enhanced MRI | Drug: P03277<br>* Single intravenous (IV) bolus injection at a rate of 2 mL/second<br>* Other names: Gadopiclenol;Drug: Gadobenate dimeglumine<br>* Single IV bolus injection at a rate of 2 mL/second<br>* Other names: MultiHance;Device: MRI<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Contrast to Noise Ratio (CNR) Difference | The Contrast-to-Noise Ratio (CNR) was calculated from the signal intensity measurement of maximum 3 enhanced lesions by 3 independent blinded readers. Only lesions detected by both MRIs after lesion tracking were used. The difference in CNR was calculated as follow: CNR (P03277) - CNR (gadobenate dimeglumine). | 1 day procedure |