Clinical trial NCT02633501: P03277 Dose Finding Study in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
Official title: P03277 Dose Finding Study in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: CNS Lesion
Blood Brain Barrier Defect
Lead sponsor: Guerbet
Sponsor class: INDUSTRY
First posted: 2015-12-17
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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).

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.

Primary outcomes:
measure: Contrast to Noise Ratio (CNR) Difference
timeFrame: 1 day procedure
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern memorial hospital
state: Illinois
city: Boston
country: United States
facility: Beth israel deaconess medical center
state: Massachusetts
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: Hershey
country: United States
facility: Penn State milton S. Hershey Medical center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pensylvania medical center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple university hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: University of texas McGovern medical school
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Antwerp
country: Belgium
facility: ZNA campus Middelheim
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Budapest
country: Hungary
facility: Neurology Clinic-Semmelweis Medical University
city: Pécs
country: Hungary
facility: Pecsi Tudomany Egyetem Klinikai kozpont Idegsebeszeti Klinica
city: Ancona
country: Italy
facility: Ospedali Riuniti di Ancona
city: Milano
country: Italy
facility: Ospedale san Raffaele
city: Roma
country: Italy
facility: AO S. Andrea Universita La Sapienza
city: Roma
country: Italy
facility: Azienda policlinico Umberto
city: Seoul
country: Korea, Republic of
facility: Asan medical center
city: Seoul
country: Korea, Republic of
facility: Samsung medical center
city: Seoul
country: Korea, Republic of
facility: Seoul National university hospital
city: Mexico City
country: Mexico
facility: Centro medico ABC santa fe
city: Monterrey
country: Mexico
facility: Axis heilsa
city: Tlanepantla De Baz
country: Mexico
facility: Clinical research institute SC
city: Gliwice
country: Poland
facility: Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie, Oddzial w Gliwicach
city: Kraków
country: Poland
facility: krakowski Szpital specjalistyczny il Jana Pawla II
city: Lublin
country: Poland
facility: Samodzielny publiczny szpital
Study officials:
affiliation: University Hospital Heidelberg
name: Martin BENDSZUS, MD
role: PRINCIPAL_INVESTIGATOR
References: