CNS LesionPhase 2NCT02633501

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

A Phase 2 study testing P03277, Gadobenate dimeglumine and MRI in people with CNS Lesion and Blood Brain Barrier Defect, run by Guerbet at 28 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: CNS Lesion, Blood Brain Barrier Defect
What is being tested?: P03277, Gadobenate dimeglumine and MRI
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 312 participants
Where: 28 sitesin 8 countries
Study dates: Jun 2016to Jan 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

28 sites in 8 countries.

Country

City, postcode or hospital

28 sites in 8 countries

United States10 sites

Beth israel deaconess medical center
Boston, Massachusetts, 02215
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern memorial hospital
Chicago, Illinois, 60611
QUEST Research Institute
Farmington Hills, Michigan, 48334
Penn State milton S. Hershey Medical center
Hershey, Pennsylvania, 17033
University of texas McGovern medical school
Houston, Texas, 77030
University of Pensylvania medical center
Philadelphia, Pennsylvania, 19104
Temple university hospital
Philadelphia, Pennsylvania, 19140
Rhode Island hospital
Providence, Rhode Island, 02903
University of Washington
Seattle, Washington, 98195

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Italy4 sites

Ospedali Riuniti di Ancona
Ancona
Ospedale san Raffaele
Milan
AO S. Andrea Universita La Sapienza
Roma
Azienda policlinico Umberto
Roma

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Mexico3 sites

Centro medico ABC santa fe
Mexico City
Axis heilsa
Monterrey
Clinical research institute SC
Tlalnepantla

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Poland3 sites

Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie, Oddzial w Gliwicach
Gliwice
krakowski Szpital specjalistyczny il Jana Pawla II
Krakow
Samodzielny publiczny szpital
Lublin

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South Korea3 sites

Asan medical center
Seoul
Samsung medical center
Seoul
Seoul National university hospital
Seoul

Other trials in South Korea

Belgium2 sites

ZNA campus Middelheim
Antwerp
Universitair Ziekenhuis Brussel
Brussels

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Hungary2 sites

Neurology Clinic-Semmelweis Medical University
Budapest
Pecsi Tudomany Egyetem Klinikai kozpont Idegsebeszeti Klinica
Pécs

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Czechia1 site

Fakultni nemocnice Olomouc
Olomouc

Other trials in Czechia

About this study

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.

Read the 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
Being tested: P03277, Gadobenate dimeglumine, MRI

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

P03277Drug
Also called Gadopiclenol
Single intravenous (IV) bolus injection at a rate of 2 mL/second
Gadobenate dimeglumineDrug
Also called MultiHance
Single IV bolus injection at a rate of 2 mL/second
MRIDevice

Study groups in NCT02633501
Study group	Role	What they receive
Subset 1 Arm 1	Experimental	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 Receives: Drug: P03277; Drug: Gadobenate dimeglumine; Device: MRI
Subset 1 Arm 2	Experimental	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 Receives: Drug: P03277; Drug: Gadobenate dimeglumine; Device: MRI
Subset 2 Arm 1	Experimental	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 Receives: Drug: P03277; Drug: Gadobenate dimeglumine; Device: MRI
Subset 2 Arm 2	Experimental	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 Receives: Drug: P03277; Drug: Gadobenate dimeglumine; Device: MRI

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 1 day procedure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2016Jan 2018

First posted17 Dec 2015 (estimated)
Study startJun 2016
Primary completionJan 2018
Study completionJan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for CNS LesionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 312 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02633501
Sponsor's protocol ID: GDX-44-004
Status last verified: Oct 2021
First submitted: 15 Dec 2015
Last updated: 25 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: P03277 Dose Finding Study in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
ClinicalTrials.gov ID: NCT02633501
Acronym / sponsor ID: GDX-44-004
Conditions: CNS Lesion, Blood Brain Barrier Defect
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 312 participants (actual)
Lead sponsor: GuerbetIndustry (pharma, biotech, devices)
Study start: Jun 2016 (actual)
Primary completion: Jan 2018 (actual)
Study completion: Jan 2018 (actual)
First posted: 17 Dec 2015 (estimated)
Results: Posted 8 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Subset 1 Arm 1	Experimental	Drug: P03277, Drug: Gadobenate dimeglumine, Device: MRIOne 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	Experimental	Drug: P03277, Drug: Gadobenate dimeglumine, Device: MRIGadobenate 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	Experimental	Drug: P03277, Drug: Gadobenate dimeglumine, Device: MRIOne 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	Experimental	Drug: P03277, Drug: Gadobenate dimeglumine, Device: MRIGadobenate 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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.

Key exclusion criteria (1 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
P03277Also: GadopiclenolSingle intravenous (IV) bolus injection at a rate of 2 mL/second	Drug	Subset 1 Arm 1, Subset 1 Arm 2, Subset 2 Arm 1, Subset 2 Arm 2
Gadobenate dimeglumineAlso: MultiHanceSingle IV bolus injection at a rate of 2 mL/second	Drug	Subset 1 Arm 1, Subset 1 Arm 2, Subset 2 Arm 1, Subset 2 Arm 2
MRI	Device	Subset 1 Arm 1, Subset 1 Arm 2, Subset 2 Arm 1, Subset 2 Arm 2

Primary outcome

Contrast to Noise Ratio (CNR) Difference
Time frame: 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).

Results and safety

Results posted to the registry on 8 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Subset 1 - P03277 0.05 mmol/kg/Gadobenate Dimeglumine	14	12
Subset 1 - P03277 0.1 mmol/kg/Gadobenate Dimeglumine	14	11
Subset 2 - P03277 0.025 mmol/kg/Gadobenate Dimeglumine	62	55
Subset 2 - P03277 0.05 mmol/kg/Gadobenate Dimeglumine	63	59
Subset 2 - P03277 0.1 mmol/kg/Gadobenate Dimeglumine	64	53
Subset 2 - P03277 0.2 mmol/kg/Gadobenate Dimeglumine	63	48

Primary outcome: Contrast to Noise Ratio (CNR) Difference

Time frame: 1 day procedure. Least squares mean (95% Confidence Interval). Unit: Ratio

Measure	P03277 0.025 mmol/kg - Gadobenate Dimeglumine - Reader 1 n = 54	P03277 0.05 mmol/kg - Gadobenate Dimeglumine - Reader 1 n = 56	P03277 0.1 mmol/kg - Gadobenate Dimeglumine - Reader 1 n = 51	P03277 0.2 mmol/kg - Gadobenate Dimeglumine - Reader 1 n = 44	P03277 0.025 mmol/kg - Gadobenate Dimeglumine - Reader 2 n = 44	P03277 0.05 mmol/kg - Gadobenate Dimeglumine - Reader 2 n = 47	P03277 0.1 mmol/kg - Gadobenate Dimeglumine - Reader 2 n = 43	P03277 0.2 mmol/kg - Gadobenate Dimeglumine - Reader 2 n = 41	P03277 0.025 mmol/kg - Gadobenate Dimeglumine - Reader 3 n = 49	P03277 0.05 mmol/kg - Gadobenate Dimeglumine - Reader 3 n = 51	P03277 0.1 mmol/kg - Gadobenate Dimeglumine - Reader 3 n = 45	P03277 0.2 mmol/kg - Gadobenate Dimeglumine - Reader 3 n = 42
Value	-10.59 (-14.59 to -6.58)	2.18 (-2.67 to 7.03)	8.66 (3.52 to 13.79)	14.45 (7.64 to 21.25)	-14.14 (-23.33 to -4.95)	1.91 (-7.28 to 11.10)	19.38 (11.42 to 27.34)	38.37 (18.62 to 58.12)	-23.96 (-33.78 to -14.13)	2.47 (-8.39 to 13.32)	29.23 (16.05 to 42.41)	51.96 (30.36 to 73.55)

P03277 0.025 mmol/kg - Gadobenate Dimeglumine - Reader 1: Least Squares Mean: -10.59, Mixed Models Analysis
P03277 0.05 mmol/kg - Gadobenate Dimeglumine - Reader 1: Least Squares Mean: 2.18, p = 0.1858, Mixed Models Analysis
P03277 0.1 mmol/kg - Gadobenate Dimeglumine - Reader 1: Least Squares Mean: 8.66, p = 0.0007, Mixed Models Analysis

Population analysed: The analysis was done for each of the 3 independent off-site readers using the Per Protocol Set that included all subjects without major protocol deviations. A subject was analyzed as soon as he had a matching evaluation of the CNR at both MRIs by at least 1 off-site reader. Therefore, the numbers of subjects analyzed by reader could be different.

Adverse events

Time frame: Adverse events were recorded from informed consent signature up to one day after the second MRI, up to 22 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
P03277 0.025 mmol/kg	0 of 56 (0%)	14 of 56 (25%)	0 of 56
P03277 0.05 mmol/kg	0 of 74 (0%)	12 of 74 (16.2%)	0 of 74
P03277 0.1 mmol/kg	1 of 70 (1.4%)	19 of 70 (27.1%)	0 of 70
P03277 0.2 mmol/kg	1 of 56 (1.8%)	18 of 56 (32.1%)	0 of 56
Gadobenate Dimeglumine	2 of 256 (0.8%)	57 of 256 (22.3%)	0 of 256

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Martin BENDSZUS, MD principal investigator

University Hospital Heidelberg

28 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing P03277, Gadobenate dimeglumine and MRI in people with CNS Lesion and Blood Brain Barrier Defect, run by Guerbet at 28 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States, Italy, Mexico, Poland, South Korea and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Contrast to Noise Ratio (CNR) Difference (time frame: 1 day procedure). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02633501.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2021.