check_circleStudy Completed

Contrast enhancement in magnetic resonance imaging, Central nervous system pathology

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

Trial purpose

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.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - 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)
  • - 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)

Trial summary

Enrollment Goal
303
Trial Dates
July 2023 - May 2024
Phase
Phase 3
Could I Receive a placebo
No
Products
Gadoquatrane (BAY1747846)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
SUN YAT-SEN MEMORIAL HOSP. SUN YAT-SEN UNIV.Guangzhou, 510120, China
Completed
UMHAT Alexandrovska EADSofia, 1431, Bulgaria
Completed
Centro de Diagnóstico Dr. Enrique RossiBuenos Aires, C1425BEE, Argentina
Completed
Sanatorio Allende | Departamento de Investigación ClínicaCórdoba, X5000JHQ, Argentina
Active, not recruiting
Fundacion Cientifica del Sur | Centro de Lomas de Zamora - Imaging Interventionism DepartmentLomas de Zamora, Buenos Aires, B1832BRQ, Argentina
Completed
Sanatorio Otamendi | Imaging Diagnostic CenterBuenos Aires, C1115AAB, Argentina
Completed
Clinica Universitaria Reina Fabiola | Consultorios ExternosCordoba, X5004FHP, Argentina
Completed
Beijing Tiantan Hospital, Captial Medical UniversityBeijing, 100050, China
Completed
The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, 325000, China
Completed
The First Affiliated Hospital of Jinan UniversityGuangzhou, 510630, China
Completed
Nanfang Hospital, Southern Medical UniversityGuangzhou, 510515, China
Active, not recruiting
Beijing Chaoyang Hospital, Capital Medical UniversityBeijing, 100020, China
Completed
Seoul National University HospitalSeoul, 3080, Korea, Republic Of
Withdrawn
Asan Medical CenterSeoul, 138-736, Korea, Republic Of
Completed
Konkuk University Medical CenterSeoul, 5030, Korea, Republic Of
Withdrawn
Ajou University HospitalSuwon, 443-721, Korea, Republic Of
Active, not recruiting
Charing Cross HospitalLondon, W6 8RF, United Kingdom
Completed
Trial Pharma Kft. SzegedSzeged, 6726, Hungary
Completed
Idegsebeszeti KlinikaPecs, 7623, Hungary
Completed
Debreceni Egyetem Klinikai Kozpont, Idegsebeszeti KlinikaDebrecen, 4032, Hungary
Withdrawn
Kistarcsai Flor Ferenc KorhazKistarcsa, 2143, Hungary
Withdrawn
Semmelweis Egyetem Idegsebeszeti es Neurointervencios KlinikaBudapest, 1145, Hungary
Completed
Szent Damjan Gorogkatolikus KorhazKisvarda, 4600, Hungary
Completed
Queen Elizabeth University HospitalGlasgow, G51 4TF, United Kingdom
Withdrawn
Royal Infirmary of EdinburghEdinburgh, EH16 4SA, United Kingdom
Not yet recruiting
University Hospital of WalesCardiff, CF14 4XW, United Kingdom
Completed
Fakultni nemocnice Plzen - LochotinPlzen, 32300, Czechia
Completed
Vseobecna fakultni nemocnice v PrazePraha 2, 12808, Czechia
Completed
Fakultni nemocnice OstravaOstrava, 708 52, Czechia
Completed
Fakultni Thomayerova NemocnicePrague, 140 59, Czechia
Withdrawn
Medical University of South Carolina - RadiologyCharleston, 29425, United States
Completed
University of Missouri -Radiology - ColumbiaColumbia, 65212, United States
Withdrawn
University of Connecticut Health CenterFarmington, 06032, United States
Withdrawn
University of California Irvine Med. Center / Diagnostic Radiology, NeuroradiologyOrange, 92868, United States
Completed
Halo DiagnosticsIndian Wells, 92210, United States
Withdrawn
Penn State Milton S. Hershey Medical CenterHershey, 17033, United States
Completed
QUEST Research Institute | Farmington Hills, MIFarmington Hills, 48334, United States
Completed
Northwestern University - Dept. of RadiologyChicago, 60611, United States
Completed
Fakultni nemocnice BrnoBrno, 625 00, Czechia
Withdrawn
Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnicePardubice, 530 03, Czechia
Completed
Instituto Alexander Fleming | Sede Central - Departamento de Diagnostico por ImagenesCABA, C1426, Argentina
Withdrawn
Borsod-Abauj-Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktatokorhaz, Kozponti Diagnosztikai CentrumMiskolc, 3526, Hungary
Completed
ASST Papa Giovanni XXIIIBergamo, 24127, Italy
Withdrawn
Ospedale San Raffaele s.r.l.Milano, 20132, Italy
Completed
A.O.U. Sant'AndreaRoma, 00189, Italy
Completed
ASL Provincia di Barletta-Andria-TraniAndria, 70031, Italy
Completed
Uniklinik Kiel /Radiologie und NeuroradiologieKiel, 24105, Germany
Completed
Universitätsklinikum EssenEssen, 45122, Germany
Completed
St. Franziskus-Hospital GmbHMünster, 48145, Germany
Completed
Uniklinik Augsburg / RadiologieAugsburg, 86156, Germany
Withdrawn
University of Texas Southwestern Medical CenterDallas, 75235-3858, United States
Completed
Uppsala University Hospital, Neuroradiology DepartmentUppsala, 75185, Sweden
Completed
Karolinska University Hospital, Huddinge NeuroradiologyStockholm, 141 86, Sweden
Completed
Karolinska University Hospital, Solna NeuroradiologyStockholm, 17177, Sweden
Completed
University Multiprofile Hospital for Active Treatment St. Ivan Rilski | Radiology DepartmentSofia, 1431, Bulgaria
Completed
University Multiprofile Hospital for Active Treatment Prof. Dr. Alexander Chirkov EADSofia, 1431, Bulgaria
Withdrawn
Acibadem City Clinic Multiprofile Hospital for Active TreatmSofia, 1407, Bulgaria
Completed
UMHAT Tsaritsa Joanna-ISUL EAD SofiaSofia, 1606, Bulgaria
Completed
University Multiprofile Hospital for Active Treatment Sveti Georgi | Base II - Imaging Diagnostic DepartmentPlovdiv, 4002, Bulgaria
Completed
MHAT Sveta Marina EADVarna, 9010, Bulgaria
Completed
Multiprofile Hospital for Active Treatment Central Onco Hospital | Independent Medical Diagnostic Laboratory MediscanPlovdiv, 4002, Bulgaria
Completed
Peking University First HospitalBeijing, 100034, China
Completed
Osaka City General HospitalOsaka, 534-0021, Japan
Completed
Social Medical Corporation the Chiyukai foundation Fukuoka Wajiro HospitalFukuoka, 811-0213, Japan
Completed
National Hospital Organization Kyushu Medical CenterFukuoka, 810-8563, Japan
Withdrawn
Hospital of the University of Occupational and Environmental Health, JapanKitakyushu, 807-8556, Japan
Withdrawn
Hokkaido University HospitalSapporo, 060-8648, Japan
Completed
Shonan Fujisawa Tokushukai HospitalFujisawa, 251-0041, Japan
Completed
National Hospital Organization Kanazawa Medical Center | Clinical Trial Management OfficeKanazawa, 920-8650, Japan
Withdrawn
Princess Margaret Hospital-University Health NetworkToronto, M5G 2M9, Canada
Active, not recruiting
Hopital du Sacre-Coeur de MontrealMontreal, QC H4J 1C5, Canada
Withdrawn
St.Joseph's Health Care-LondonLondon, N6G 2M3, Canada
Completed
Japan Organization of Occupational Health and Safety Kagawa Rosai HospitalMarugame, 763-8502, Japan
Completed
Huai'an First People's Hospital, Nanjing Medical UniversityHuai'An, 223300, China
Completed
Zhongda Hospital Southeast UniversityNanjing, 210009, China
Completed
Binali Yildirim Universitesi Mengucek Gazi EAH - Radyolojierzincan, 24610, Turkey
Completed
Istanbul Universitesi Istanbul Tip FakultesiIstanbul, 34093, Turkey
Completed
Koc Universitesi Tip Fakultesi - RadyolojiIstanbul, 34010, Turkey
Withdrawn
Lokman Hekim Universitesi Tip Fakultesi - RadyolojiAnkara, 06510, Turkey
Completed
Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip FakultesiIstanbul, 34098, Turkey
Not yet recruiting
Hacettepe Universitesi Tip FakultesiAnkara, 06532, Turkey
Not yet recruiting
Ondokuz Mayis Uni Tip FakultesiSamsun, 55139, Turkey
Completed
Kishiwada Tokushukai HospitalKishiwada, 596-0042, Japan
Completed
Centre Hospitalier Lyon SudPIERRE BENITE, 69495, France
Completed
Center Hospitalier Michallon - GrenobleLA TRONCHE, 38700, France
Completed
CHU STRASBOURG - Hôpital de HautepierreSTRASBOURG CEDEX, 67098, France
Completed
Hyogo Prefectural Nishinomiya HospitalNishinomiya, 662-0918, Japan
Completed
Kure Kyosai HospitalKure, 737-8505, Japan
Completed
National Hospital Organization Kanmon Medical CenterShimonoseki, 752-8510, Japan
Withdrawn
Mayo Clinic - RochesterRochester, 55905, United States
Completed
London Health Sciences Centre (LHSC) - University HospitalLondon, N6A 5A5, Canada
Completed
Duke University School of MedicineDurham, 27710, United States
Completed
Inje University Busan Paik HospitalBusan, 47392, Korea, Republic Of
Completed
Biogenix Molecular, LLCMiami, 33165, United States

Primary Outcome

  • Visualization parameter contrast Enhancement assessed by separate blinded evaluation of unenhanced and combined pre- and post-gadoquatrane MRI, by a BICR
    Contrast Enhancement will be assessed on a 4-point scale (1/No: not enhanced, 2/Moderate: weakly enhanced, 3/Good: clearly enhanced, 4/Excellent: clearly and brightly enhanced). BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging
    date_rangeTime Frame:
    1 day procedure
  • Visualization parameter delineation assessed by separate blinded evaluation of unenhanced and combined pre- and post-gadoquatrane MRI, by a BICR
    Delineation will be assessed on a 4-point scale (1/No: no or unclear delineation, 2/Moderate: some aspects of delineation, 3/Good: almost clear but not complete, 4/Excellent: clear and complete delineation). BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging
    date_rangeTime Frame:
    1 day procedure
  • Visualization parameter morphology assessed by separate blinded evaluation of unenhanced and combined pre- and post-gadoquatrane MRI, by a BICR
    Morphology will be assessed on a 3-point scale (1/Poor: no or poorly evaluable, 2/Moderate: partially evaluable, 3/Good: sufficiently evaluable). BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging
    date_rangeTime Frame:
    1 day procedure

Secondary Outcome

  • 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
    Contrast Enhancement will be assessed on a 4-point scale (1/No: not enhanced, 2/Moderate: weakly enhanced, 3/Good: clearly enhanced, 4/Excellent: clearly and brightly enhanced). BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    Delineation will be assessed on a 4-point scale (1/No: no or unclear delineation, 2/Moderate: some aspects of delineation, 3/Good: almost clear but not complete, 4/Excellent: clear and complete delineation). BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    Morphology will be assessed on a 3-point scale (1/Poor: no or poorly evaluable, 2/Moderate: partially evaluable, 3/Good: sufficiently evaluable). BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • The overall diagnostic clinical value of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs
    The overall diagnostic clinical value is composed of 2 elements and based on: i.the evaluation of diagnostic descriptive imaging features adapted from radiologic reporting standards (detection/exclusion of enhancing pathology; location, extent, and pattern of enhancement) on a 5-point scale (1- no diagnostic clinical value from contrast enhancement, 2- poor diagnostic clinical value from contrast enhancement, 3- moderate diagnostic clinical value from contrast enhancement, 4- good diagnostic clinical value from contrast enhancement, 5- excellent diagnostic clinical value from contrast enhancement), by the BICR and the Investigator; ii. the evaluation of patient management based on the diagnostic reporting recommendations (i.e., likely diagnosis), by the Investigator. BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging
    date_rangeTime Frame:
    1 day procedure
  • 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
    BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • Diagnoses from combined pre- and post- gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs by the Investigator
    BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    The degree of confidence will be rated on a 4-point scale: 1 = Not confident, 2 = Somewhat confident, 3 = Confident, 4 = Very confident. BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    BICR = blinded independent central read / blinded independent central readers; MRI = magnetic resonance imaging; GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    1 day procedure
  • 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
    GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    Within 24 ± 4 hours after administration of gadoquatrane or any approved macrocyclic GBCAs
  • 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
    GBCAs = gadolinium-based contrast agents
    date_rangeTime Frame:
    Within 24 ± 4 hours after administration of gadoquatrane or any approved macrocyclic GBCAs

Trial design

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)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Diagnostic
Allocation
Randomized
Blinding
N/A
Assignment
Crossover Assignment
Trial Arms
2