Clinical trial NCT05915702: A Study to Compare How Well Gadoquatrane Works and Its Safety With an Already Available Contrast Agent for MRI in People With Known or Suspected Brain or Spinal Cord-related Problems
Official title: A Multicenter, Randomized, Prospective Double-blind, Cross-over Phase 3 Study to Evaluate the Efficacy and Safety of 0.04 mmol Gd/kg Body Weight of Gadoquatrane for MRI in Adults With Known or Suspected Pathology of the Central Nervous System (CNS), Compared to 0.1 mmol Gd/kg Approved Macrocyclic Gadolinium-based Contrast Agents (GBCAs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Contrast Enhancement in Magnetic Resonance Imaging
Central Nervous System Pathology
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2023-06-23
Enrollment: 303
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: Researchers are looking for a better way to help people with known or suspected brain or spinal cord-related problems scheduled for a "contrast-enhanced" Magnetic Resonance Imaging (MRI).

MRI is used by doctors to create detailed images of the inside of the body to identify health problems. Sometimes doctors need to inject a contrast agent into a patient's vein to perform a so called "contrast-enhanced" MRI (CE-MRI). Such CE-MRI examinations may support doctors to identify certain health problems or improve the evaluation.

The contrast agents commonly used in MRI are gadolinium-based contrast agents (GBCAs). GBCAs contain a "rare earth" element called gadolinium (Gd). Gadoquatrane is a new contrast agent under development with a lower amount of Gd needed per CE-MRI.

The main purpose of this study is to learn whether CE-MRI scans with gadoquatrane work better than MRI scans without the use of a contrast agent (GBCA). The researchers will compare the ability to detect brain and spinal cord-related problems in gadoquatrane-MRI scans to plain-MRI scans without the use of a contrast agent.

The participants will undergo 2 MRI scans, one with gadoquatrane and one with currently used GBCA. Both contrast agents will be injected into the vein.

Each participant will be in the study for between 6 and 42 days with up to 7 doctor visits.

At the start or during the study, the doctors and their study team will:

* take blood and urine samples
* do physical examinations
* check blood pressure and heart rate
* review the MRI scans obtained in the study and decide on the diagnosis
* ask the participants questions about how they are feeling and what adverse events they are having.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments.


Eligibility criteria: Inclusion Criteria:

* Participant must be \>= 18 years of age inclusive, at the time of signing the informed consent form
* Participants with a clinical indication for a contrast-enhanced MRI (including MRA), with any approved standard of care macrocyclic GBCA with proven efficacy, safety and tolerability in clinical routine CE-MRI/MRA (gadobutrol, gadoterate meglumine/ gadoteric acid or gadoteridol) that is used at the site for the indication, for a known or suspected CNS pathology
* Participants who can undergo study-related procedures, including 2 contrast-enhanced MRI examinations (one with gadoquatrane and one with a comparator macrocyclic GBCA), as per participant and Investigator's judgement
* Contraceptive use by female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of nonchildbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method during the study intervention period (at a minimum of 24 hours after the last dose of study intervention)

Exclusion Criteria:

* Considered clinically unstable or has a concurrent/concomitant condition that may significantly alter image comparability between the 2 study MRIs or between study parameters (e.g. safety, pharmacokinetics \[PK\] parameters) or would not allow participation for the full planned study period, in the judgement of the investigator
* Participants presenting with severe renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m\^2, derived from a serum or plasma creatinine sample obtained within 48 hours prior to the first contrast agent injection in the study
* Participants with acute kidney injury (i.e., acute renal failure), regardless of eGFR
* History of moderate to severe allergic-like reaction to any GBCA
* Bronchial asthma considered unstable or who have had recent modification to their medical therapy
* Receipt of any contrast agent \< 72 h prior to the study MRIs or planned to receive any contrast agent during the trial until 24 h +/- 4 h after the second study MRI
* Planned or expected interventional diagnostic or therapeutic procedure (e.g. biopsy or surgery in the region of interest) or change in treatment (e.g. start of chemotherapy or antiangiogenic therapy, significant change in corticosteroids dose) that may significantly alter image comparability between the 2 MRIs or other study parameters (i.e. safety/adverse events (AEs) \[e.g. confounding AEs or safety events due to surgery or chemotherapy\], PK parameters), from the first study MRI up to 24 h after the second study MRI
* Has received any investigational product within 30 days, or within 5 times half-life of the investigational product, whatever is shorter, prior to or concurrent with this study
* Contraindications to the administration of macrocyclic GBCAs (depending on local product label), or history of adverse reaction to gadoquatrane
* Any contraindication to MRI examinations based on institution policy and investigator's clinical judgement (e.g. some metallic implants or active implants)

Primary outcomes:
measure: Visualization parameter contrast Enhancement assessed by separate blinded evaluation of unenhanced and combined pre- and post-gadoquatrane MRI, by a BICR
timeFrame: 1 day procedure
measure: Visualization parameter delineation assessed by separate blinded evaluation of unenhanced and combined pre- and post-gadoquatrane MRI, by a BICR
timeFrame: 1 day procedure
measure: Visualization parameter morphology assessed by separate blinded evaluation of unenhanced and combined pre- and post-gadoquatrane MRI, by a BICR
timeFrame: 1 day procedure
Secondary outcomes:
measure: Visualization parameter contrast assessed by separate blinded evaluation of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
timeFrame: 1 day procedure
measure: Visualization parameter delineation assessed by separate blinded evaluation of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
timeFrame: 1 day procedure
measure: Visualization parameter morphology assessed by separate blinded evaluation of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
timeFrame: 1 day procedure
measure: Sensitivity for the detection of lesions of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
timeFrame: 1 day procedure
measure: Specificity for the detection of lesions of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
timeFrame: 1 day procedure
measure: The overall diagnostic clinical value of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs
timeFrame: 1 day procedure
measure: Sensitivity for the detection of malignant lesions of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs assessed by BICR and the investigator
timeFrame: 1 day procedure
measure: Specificity for the detection of malignant lesions of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs assessed by BICR and the investigator
timeFrame: 1 day procedure
measure: Diagnoses from combined pre- and post- gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs by the Investigator
timeFrame: 1 day procedure
measure: Confidence in diagnosis combined pre- and post- gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs by BICR and by Investigator on 4PS
timeFrame: 1 day procedure
measure: Number of lesions seen on unenhanced MRI image set and combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
timeFrame: 1 day procedure
measure: Number of enhancing lesions seen on combined pre- and post- gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
timeFrame: 1 day procedure
measure: Number of participants with treatment emergent adverse events, including number of serious adverse events, after administration of gadoquatrane compared to macrocyclic GBCAs reported by the investigator
timeFrame: Within 24 ± 4 hours after administration of gadoquatrane or any approved macrocyclic GBCAs
measure: Number of participants with treatment emergent adverse events, including number of serious adverse events, per intensity after administration of gadoquatrane compared to macrocyclic GBCAs reported by the investigator
timeFrame: Within 24 ± 4 hours after administration of gadoquatrane or any approved macrocyclic GBCAs
Other outcomes:
Locations:
city: Indian Wells
country: United States
facility: Halo Diagnostics - Indian Wells
state: California
city: Orange
country: United States
facility: University of California Irvine Med. Center / Diagnostic Radiology, Neuroradiology
state: California
city: Miami
country: United States
facility: Biogenix Molecular, LLC
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital - Radiology
state: Illinois
city: Farmington Hills
country: United States
facility: QUEST Research Institute | Farmington Hills, MI
state: Michigan
city: Columbia
country: United States
facility: University of Missouri -Radiology - Columbia
state: Missouri
city: Durham
country: United States
facility: Duke University School of Medicine - Early Phase Research Unit - Neurology
state: North Carolina
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Lomas De Zamora, Buenos Aires
country: Argentina
facility: Fundacion Cientifica del Sur | Centro de Lomas de Zamora - Imaging Interventionism Department
state: Buenos Aires
city: Caba
country: Argentina
facility: Instituto Alexander Fleming | Sede Central - Departamento de Diagnostico por Imagenes
state: Ciudad Auton. De Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Sanatorio Otamendi | Imaging Diagnostic Center
state: Ciudad Auton. De Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro de Diagnostico Enrique Rossi | Departamento de Investigacion Clínica
state: Ciudad Auton. De Buenos Aires
city: Cordoba
country: Argentina
facility: Clinica Universitaria Reina Fabiola | Consultorios Externos
city: Córdoba
country: Argentina
facility: Sanatorio Allende | Departamento de Investigación Clínica
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Central Onco Hospital | Independent Medical Diagnostic Laboratory Mediscan
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti Georgi | Base II - Imaging Diagnostic Department
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Multiprofile Hospital for Active Treatm
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital For Active Treatment 'Alexandrovska' EAD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Prof. Dr. Alexander Chirkov EAD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment St. Ivan Rilski | Radiology Department
city: Sofia
country: Bulgaria
facility: University Hospital for Active Treatment Tsaritsa Joanna - ISUL | Radiology Department
city: Varna
country: Bulgaria
facility: MHAT Sveta Marina EAD
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: London
country: Canada
facility: London Health Sciences Centre (LHSC) - University Hospital
city: Beijing
country: China
facility: Beijing Chaoyang Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Captial Medical University
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hosp. Sun Yat-Sen Univ.
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Huai'An
country: China
facility: Huai'an First People's Hospital, Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno - Klinika radiologie a nukleární medicíny
state: Jihomoravsky Kraj
city: Ostrava - Poruba
country: Czechia
facility: Fakultní nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnice
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen - Lochotin
city: Praha 4
country: Czechia
facility: Fakultní Thomayerova nemocnice - RDG radiodiagnostické oddelení
city: Praha
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
city: Grenoble Cedex 09
country: France
facility: Center Hospitalier Michallon - Grenoble
city: Pierre-Benite
country: France
facility: Centre Hospitalier Lyon Sud - Service d'imagerie
city: Strasbourg
country: France
facility: Centre Hospitalo-Universitaire de Strasbourg
city: Augsburg
country: Germany
facility: Uniklinik Augsburg / Radiologie
state: Bayern
city: Essen
country: Germany
facility: Universitätsklinikum Essen - Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie - 21181
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: St. Franziskus-Hospital GmbH
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Uniklinik Kiel /Radiologie und Neuroradiologie
state: Schleswig-Holstein
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont, Idegsebeszeti Klinika
city: Kisvarda
country: Hungary
facility: Szent Damjan Gorogkatolikus Korhaz
city: Pecs
country: Hungary
facility: Idegsebeszeti Klinika
city: Szeged
country: Hungary
facility: Trial Pharma Kft. Szeged
city: Roma
country: Italy
facility: Azienda Ospedaliero-Universitaria Sant'Andrea - UOC Neuroradiologia
state: Lazio
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII - Radiologia diagnostica per immagini 2 Neuroradiologia
state: Lombardia
city: Andria
country: Italy
facility: ASL Della Provincia Di Barletta Andria Trani_Ospedale L.Bonomo - Radiodiagnostica
state: Puglia
city: Kure
country: Japan
facility: Kure Kyosai Hospital
state: Hiroshima
city: Nishinomiya
country: Japan
facility: Hyogo Prefectural Nishinomiya Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center | Clinical Trial Management Office
state: Ishikawa
city: Marugame
country: Japan
facility: Japan Organization of Occupational Health and Safety Kagawa Rosai Hospital
state: Kagawa
city: Fujisawa
country: Japan
facility: Shonan Fujisawa Tokushukai Hospital
state: Kanagawa
city: Kishiwada
country: Japan
facility: Kishiwada Tokushukai Hospital
state: Osaka
city: Shimonoseki
country: Japan
facility: National Hospital Organization Kanmon Medical Center
state: Yamaguchi
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Fukuoka
country: Japan
facility: Social Medical Corporation the Chiyukai foundation Fukuoka Wajiro Hospital
city: Osaka
country: Japan
facility: Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Huddinge Neuroradiology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Solna Neuroradiology
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Neuroradiology Department
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Erzincan
country: Turkey
facility: Binali Yildirim Universitesi Mengucek Gazi EAH - Radyoloji
city: Istanbul
country: Turkey
facility: Koc Universitesi Tip Fakultesi - Radyoloji
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi
city: Samsun
country: Turkey
facility: Ondokuz Mayis Uni Tip Fakultesi
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
state: Glasgow City
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: Charing Cross Hospital
Study officials:
References: