Performance of Elucirem® in DSC-MRI Perfusion of Brain Gliomas

Study Overview
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Brief Summary
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This trial aims to study the performance of Elucirem® (gadopiclenol) in Dynamic Susceptibility Contrast Magnetic Resonance Imaging (DSC-MRI) perfusion of brain gliomas.

Detailed Description
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The trial is designed as a prospective, multi-center, randomized, controlled and parallel group comparison. This study aims to enrol 138 patients in Italy, Poland and Hungary. During the course of the trial, patient will undergo a DSC-MRI perfusion using Elucirem® or Dotarem®. A safety visit will be performed 1 day after the MRI visit. Confirmation of tumor grade diagnosis, if available, will be collected up to 30 days after visit 2. Primary end point will be assessed by independent off-site blinded readers.

Official Title
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Performance of Elucirem® (Gadopiclenol) in Dynamic Susceptibility Contrast Magnetic Resonance Imaging (DSC-MRI) Perfusion of Brain Gliomas Phase IIIb Clinical Trial

Conditions
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Brain Tumor, Primary, Brain Tumor, Recurrent

Intervention / Treatment
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* Drug: Elucirem
* Drug: Dotarem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male adult patient (patient having reached legal majority age). Patient with naive or recurrent primary glial tumor detected at a previous Computed Tomography (CT) or MR imaging, and scheduled for a follow-up contrast-enhanced MRI. Tumor grade (confirmed or highly suspected) should be available in patients' medical records. Patient or, if the patient is unable to provide informed consent, the patient's legally acceptable representative and/or impartial witness, having read the information and having provided patient's consent to participate in writing by dating and signing the informed consent prior to any trial related procedure being conducted. Patient affiliated to national health insurance according to local regulatory requirements. Exclusion Criteria: Patient with known contra-indication(s) to the use or with known sensitivity to one of the products under investigation or to other Gadolinium-Based Contrast Agents (GBCA) (such as hypersensitivity, post-contrast acute kidney injury). Patient presenting with any contraindication to MRI examinations. Post treatment patient presenting with pseudo-progression instead of tumor recurrency. Patient presenting with severe renal insufficiency, defined as an estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m² assessed within 1 week prior to contrast agent injection. Patient having received any contrast agent (for MRI or CT) within 3 days prior to IMP administration or scheduled to receive any contrast agent within 24 hours after IMP administration. Pregnant female patient (a female patient of childbearing potential or with amenorrhea for less than 12 months must have a negative pregnancy test within 1 day prior to trial MRI and must be using medically approved contraception method until the last trial visit). Patient having received any investigational medicinal product within 7 days prior to trial entry or scheduled to receive any investigational treatment in the course of the trial. Patient previously randomized in this trial. 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 in the trial. Patient unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits and/or unlikelihood of completing the trial. Patient related to the investigator or any other trial staff or relative directly involved in the trial conduct.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elucirem®<br>Patient will undergo a DSC-MRI perfusion using Elucirem® | Drug: Elucirem<br>* Intravenous administration<br>* Other names: gadopiclenol;|
| Active Comparator: Dotarem®<br>Patient will undergo a DSC-MRI perfusion using Dotarem® | Drug: Dotarem<br>* Intravenous administration<br>* Other names: gadoteric acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate the non-inferiority of DSC-MRI perfusion using Elucirem® at 0.05 mmol/kg compared to DSC-MRI perfusion using Dotarem® at 0.1 mmol/kg in terms of diagnostic quality of Cerebral Blood Volume perfusion map | Diagnostic quality of the CBV map will be assessed by off-site readers using a 4-point scale with the grades: poor, fair, good or excellent | Evaluation is performed within 6 months after obtaining MRI scan and CBV map | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the diagnostic quality of CBV perfusion map for Elucirem® and Dotarem® (on-site assessment) | Diagnostic quality of the CBV map will be assessed by on-site readers using the same 4-point scale as the one used for primary evaluation criterion | Evaluation is performed within 1 month after obtaining MRI scan and CBV map | 
| To compare the performance of DSC-MRI perfusion using Elucirem® at 0.05 mmol/kg to DSC-MRI using Dotarem® at 0.1 mmol/kg in differentiating glioma grade through the quantification of the relative CBV (rCBV) (off-site assessment) | The rCBV will be calculated on the CBV perfusion maps generated for each DSC-MRI perfusion. The regions of interest (ROIs) will be placed by off-site readers on the tumor for providing tumor CBV and also on normal tissue (contralateral normal-appearing white matter) for providing referenced CBV. | Evaluation is performed within 6 months after obtaining MRI scan and CBV map | 
| To assess the reliability of the T2* signal intensity time curve in terms of confidence in diagnosis in DSC-MRI perfusion using Elucirem® at 0.05 mmol/kg (on-site and off-site assessments) | T2* signal intensity time curve will be visually assessed by on-site and off-site readers for the reliability of the curve in providing sufficient information for diagnosis purpose. The Full-Width at Half-Maximum (FWHM) and the maximum signal drop will be measured by off-site readers only. | Evaluation is performed within 6 months after obtaining MRI scan and CBV map | 
| To expand the previously established safety profile of Elucirem® at 0.05 mmol/kg in terms of incidence of adverse events | Adverse events, serious or not, related to IMP or not, that occur from the beginning of patient's participation in the trial (Informed Consent Form signature) until the end of the participation. | Evaluation is performed from the beginning of patient's participation in the trial (Informed Consent Form signature) until the end of the participation (maximum 37 days). |