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

Phase 2

Completed

• Conditions: CNS Lesion; Blood Brain Barrier Defect
• Interventions: Drug: P03277; Drug: Gadobenate dimeglumine; Device: MRI

• Registration Number: NCT02633501
• Lead Sponsor: Guerbet

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).

Study Timeline

• Study First Submitted: 2015-12-15
• Study First Submitted QC: 2015-12-16
• Study First Posted: 2015-12-17
• Study Start: 2016-06
• Primary Completion: 2018-01
• Study Completion: 2018-01
• Results First Submitted: 2019-01-31
• Results First Submitted QC: 2019-04-17
• Results First Posted: 2019-05-08
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-04
• Last Update Posted: 2021-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 312

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Subset 1 Arm 2	MRI	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
Subset 1 Arm 1	P03277	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
Subset 1 Arm 2	P03277	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
Subset 1 Arm 1	MRI	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
Subset 2 Arm 1	P03277	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
Subset 2 Arm 1	MRI	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
Subset 2 Arm 2	P03277	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
Subset 2 Arm 2	MRI	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
Subset 1 Arm 1	Gadobenate dimeglumine	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
Subset 1 Arm 2	Gadobenate dimeglumine	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
Subset 2 Arm 1	Gadobenate dimeglumine	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
Subset 2 Arm 2	Gadobenate dimeglumine	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

Primary Outcome Measures

Name	Time	Method
Contrast to Noise Ratio (CNR) Difference	1 day procedure	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).

Trial Locations

Locations (28)

Ospedali Riuniti di Ancona; 🇮🇹 Ancona, Italy

AO S. Andrea Universita La Sapienza; 🇮🇹 Roma, Italy

Pecsi Tudomany Egyetem Klinikai kozpont Idegsebeszeti Klinica; 🇭🇺 Pécs, Hungary

Asan medical center; 🇰🇷 Seoul, Korea, Republic of

Universitair Ziekenhuis Brussel; 🇧🇪 Brussel, Belgium

Ospedale san Raffaele; 🇮🇹 Milano, Italy

Samsung medical center; 🇰🇷 Seoul, Korea, Republic of

QUEST Research Institute; 🇺🇸 Farmington Hills, Michigan, United States

Penn State milton S. Hershey Medical center; 🇺🇸 Hershey, Pennsylvania, United States

ZNA campus Middelheim; 🇧🇪 Antwerp, Belgium

Fakultni nemocnice Olomouc; 🇨🇿 Olomouc, Czechia

Northwestern memorial hospital; 🇺🇸 Chicago, Illinois, United States

Beth israel deaconess medical center; 🇺🇸 Boston, Massachusetts, United States

University of Pensylvania medical center; 🇺🇸 Philadelphia, Pennsylvania, United States

Temple university hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

University of texas McGovern medical school; 🇺🇸 Houston, Texas, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Neurology Clinic-Semmelweis Medical University; 🇭🇺 Budapest, Hungary

Azienda policlinico Umberto; 🇮🇹 Roma, Italy

Seoul National university hospital; 🇰🇷 Seoul, Korea, Republic of

Clinical research institute SC; 🇲🇽 Tlanepantla De Baz, Mexico

Axis heilsa; 🇲🇽 Monterrey, Mexico

krakowski Szpital specjalistyczny il Jana Pawla II; 🇵🇱 Kraków, Poland

Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie, Oddzial w Gliwicach; 🇵🇱 Gliwice, Poland

Samodzielny publiczny szpital; 🇵🇱 Lublin, Poland

Centro medico ABC santa fe; 🇲🇽 Mexico City, Mexico

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Rhode Island hospital; 🇺🇸 Providence, Rhode Island, United States