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

NCT ID: NCT02633501

Last Updated: 2021-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 312 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2018-01-31

Brief Summary

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

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).

Conditions

CNS Lesion; Blood Brain Barrier Defect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous (IV) bolus injection at a rate of 2 mL/second

Gadobenate dimeglumine

Intervention Type: DRUG

Single IV bolus injection at a rate of 2 mL/second

MRI

Intervention Type: DEVICE

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

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous (IV) bolus injection at a rate of 2 mL/second

Gadobenate dimeglumine

Intervention Type: DRUG

Single IV bolus injection at a rate of 2 mL/second

MRI

Intervention Type: DEVICE

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

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous (IV) bolus injection at a rate of 2 mL/second

Gadobenate dimeglumine

Intervention Type: DRUG

Single IV bolus injection at a rate of 2 mL/second

MRI

Intervention Type: DEVICE

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

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous (IV) bolus injection at a rate of 2 mL/second

Gadobenate dimeglumine

Intervention Type: DRUG

Single IV bolus injection at a rate of 2 mL/second

MRI

Intervention Type: DEVICE

Interventions

P03277

Single intravenous (IV) bolus injection at a rate of 2 mL/second

Intervention Type: DRUG

Gadobenate dimeglumine

Single IV bolus injection at a rate of 2 mL/second

Intervention Type: DRUG

MRI

Intervention Type: DEVICE

Other Intervention Names

Gadopiclenol; MultiHance

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guerbet

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin BENDSZUS, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Heidelberg

Locations

Northwestern memorial hospital

Chicago, Illinois, United States

Beth israel deaconess medical center

Boston, Massachusetts, United States

QUEST Research Institute

Farmington Hills, Michigan, United States

Penn State milton S. Hershey Medical center

Hershey, Pennsylvania, United States

University of Pensylvania medical center

Philadelphia, Pennsylvania, United States

Temple university hospital

Philadelphia, Pennsylvania, United States

Rhode Island hospital

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of texas McGovern medical school

Houston, Texas, United States

University of Washington

Seattle, Washington, United States

ZNA campus Middelheim

Antwerp, , Belgium

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Neurology Clinic-Semmelweis Medical University

Budapest, , Hungary

Pecsi Tudomany Egyetem Klinikai kozpont Idegsebeszeti Klinica

Pécs, , Hungary

Ospedali Riuniti di Ancona

Ancona, , Italy

Ospedale san Raffaele

Milan, , Italy

AO S. Andrea Universita La Sapienza

Roma, , Italy

Azienda policlinico Umberto

Roma, , Italy

Centro medico ABC santa fe

Mexico City, , Mexico

Axis heilsa

Monterrey, , Mexico

Clinical research institute SC

Tlalnepantla, , Mexico

Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie, Oddzial w Gliwicach

Gliwice, , Poland

krakowski Szpital specjalistyczny il Jana Pawla II

Krakow, , Poland

Samodzielny publiczny szpital

Lublin, , Poland

Asan medical center

Seoul, , South Korea

Samsung medical center

Seoul, , South Korea

Seoul National university hospital

Seoul, , South Korea

Countries

United States; Belgium; Czechia; Hungary; Italy; Mexico; Poland; South Korea

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GDX-44-004

Identifier Type: -

Identifier Source: org_study_id