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

Blood Brain Barrier Defect Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02633501
• Other study ID #: GDX-44-004
• Status: Completed
• Phase: Phase 2
• Start date: June 2016
• Est. completion date: January 2018

Study information

• Verified date: October 2021
• Source: Guerbet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Blood Brain Barrier Defect
• CNS Lesion

Intervention

Drug:
• P03277
Single intravenous (IV) bolus injection at a rate of 2 mL/second
• Gadobenate dimeglumine
Single IV bolus injection at a rate of 2 mL/second

Device:
• MRI

Locations

Country	Name	City	State
Belgium	ZNA campus Middelheim	Antwerp
Belgium	Universitair Ziekenhuis Brussel	Brussel
Czechia	Fakultni nemocnice Olomouc	Olomouc
Hungary	Neurology Clinic-Semmelweis Medical University	Budapest
Hungary	Pecsi Tudomany Egyetem Klinikai kozpont Idegsebeszeti Klinica	Pécs
Italy	Ospedali Riuniti di Ancona	Ancona
Italy	Ospedale san Raffaele	Milano
Italy	AO S. Andrea Universita La Sapienza	Roma
Italy	Azienda policlinico Umberto	Roma
Korea, Republic of	Asan medical center	Seoul
Korea, Republic of	Samsung medical center	Seoul
Korea, Republic of	Seoul National university hospital	Seoul
Mexico	Centro medico ABC santa fe	Mexico City
Mexico	Axis heilsa	Monterrey
Mexico	Clinical research institute SC	Tlanepantla De Baz
Poland	Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie, Oddzial w Gliwicach	Gliwice
Poland	krakowski Szpital specjalistyczny il Jana Pawla II	Kraków
Poland	Samodzielny publiczny szpital	Lublin
United States	Beth israel deaconess medical center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern memorial hospital	Chicago	Illinois
United States	QUEST Research Institute	Farmington Hills	Michigan
United States	Penn State milton S. Hershey Medical center	Hershey	Pennsylvania
United States	University of texas McGovern medical school	Houston	Texas
United States	Temple university hospital	Philadelphia	Pennsylvania
United States	University of Pensylvania medical center	Philadelphia	Pennsylvania
United States	Rhode Island hospital	Providence	Rhode Island
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Guerbet

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Hungary,  Italy,  Korea, Republic of,  Mexico,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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