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

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.

Study Overview

• Status: Completed
• Conditions: Blood Brain Barrier Defect; CNS Lesion
• Intervention / Treatment: Device: MRI; Drug: P03277; Drug: Gadobenate dimeglumine

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • ZNA Campus Middelheim
  • Brussel, Belgium
    • Universitair Ziekenhuis Brussel
• Czechia
  • Olomouc, Czechia
    • Fakultni nemocnice Olomouc
• Hungary
  • Budapest, Hungary
    • Neurology Clinic-Semmelweis Medical University
  • Pécs, Hungary
    • Pecsi Tudomany Egyetem Klinikai kozpont Idegsebeszeti Klinica
• Italy
  • Ancona, Italy
    • Ospedali Riuniti di Ancona
  • Milano, Italy
    • Ospedale San Raffaele
  • Roma, Italy
    • AO S. Andrea Universita La Sapienza
  • Roma, Italy
    • Azienda Policlinico Umberto
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
• Mexico
  • Mexico City, Mexico
    • Centro Medico ABC Santa Fe
  • Monterrey, Mexico
    • Axis heilsa
  • Tlanepantla De Baz, Mexico
    • Clinical research institute SC
• Poland
  • Gliwice, Poland
    • Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie, Oddzial w Gliwicach
  • Kraków, Poland
    • krakowski Szpital specjalistyczny il Jana Pawla II
  • Lublin, Poland
    • Samodzielny Publiczny Szpital
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pensylvania medical center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • University of texas McGovern medical school
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subset 1 Arm 1; 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	Device: MRI; Drug: P03277; Single intravenous (IV) bolus injection at a rate of 2 mL/second; Other Names: Gadopiclenol; Drug: Gadobenate dimeglumine; Single IV bolus injection at a rate of 2 mL/second; Other Names: MultiHance
Experimental: Subset 1 Arm 2; 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	Device: MRI; Drug: P03277; Single intravenous (IV) bolus injection at a rate of 2 mL/second; Other Names: Gadopiclenol; Drug: Gadobenate dimeglumine; Single IV bolus injection at a rate of 2 mL/second; Other Names: MultiHance
Experimental: Subset 2 Arm 1; 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	Device: MRI; Drug: P03277; Single intravenous (IV) bolus injection at a rate of 2 mL/second; Other Names: Gadopiclenol; Drug: Gadobenate dimeglumine; Single IV bolus injection at a rate of 2 mL/second; Other Names: MultiHance
Experimental: Subset 2 Arm 2; 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	Device: MRI; Drug: P03277; Single intravenous (IV) bolus injection at a rate of 2 mL/second; Other Names: Gadopiclenol; Drug: Gadobenate dimeglumine; Single IV bolus injection at a rate of 2 mL/second; Other Names: MultiHance

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Guerbet
• Investigators: Principal Investigator: Martin BENDSZUS, MD, University Hospital Heidelberg

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: December 16, 2015
• First Posted (Estimate): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: GDX-44-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No