check_circleStudy Completed

Central Nervous System Pathology

Bayer Identifier:

20241

ClinicalTrials.gov Identifier:

NCT04307186

EudraCT Number:

2019-001560-30

EU CT Number:

Not Available
Study to find the appropriate dose of a new gadolinium-based contrast agent (GBCA) for adults undergoing magnetic resonance imaging (MRI) for known or highly suspected brain and/or spinal cord conditions

Trial purpose

Researchers in this study want to find the appropriate dose of drug BAY1747846 for adults undergoing MRI for known or highly suspected brain and/or spinal cord conditions so that the image quality is similar to that of drug gadobutrol for adults undergoing MRI. MRI stands for Magnetic resonance imaging which produces body pictures created by using magnetic energy rather than x-ray energy.
Both BAY1747846 and gadobutrol are medicinal products known as gadolinium-based contrast agents (GBCA) which are used in MRI examinations to provide contrast enhancement and improve imaging performance. Gadobutrol (brand name: Gadavist, Gadovist) has been approved worldwide for the diagnosis of various disorders in adult and pediatric patients. BAY1747846 is a new GBCA under development with the goal to provide similar imaging performances in MRI. Participants in this study will receive both BAY1747846 and gadobutrol with a period of 3 - 14 days in between. A MRI examination will be performed after each injection. Participant will stay in this study for 2 - 4 weeks depending on the scheduling of the visits.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - Participant must be at least 18 years of age at the time of signing the informed consent.
    - Known or highly suspected CNS pathology (contrast-enhancing CNS lesion) referred for contrast-enhanced MRI of the CNS.
    - Male and female.
    - Estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min/1.73m^2.
  • - Considered clinically unstable or has a concomitant/intercurrent condition (e.g. COVID-19 infection) that would not allow participation for the full planned study period (i.e. period 1, 2 or both) in the judgement of the investigator.
    - Severe cardiovascular disease.
    - Patients undergoing liver transplantation.
    - Any contraindication to MRI examinations.
    - History of severe allergic or anaphylactic/anaphylactoid reaction to any allergen including drugs and contrast agents, foods, chemicals or other substances.
    - History of allergic asthma and/ or atopic dermatitis.
    - Suspected lesions or suffering from any of the following CNS diseases/lesion types as the main indication for MRI:
     -- Lepto-meningeal disease (e.g. leptomeningeal carcinomatosis). Dural lesions (e.g. meningiomas) fulfilling inclusion criteria #2 are not excluded
     -- Pituitary adenomas (macro and micro)
     -- Tumors of the choroid plexus
     -- Tumors of the pineal gland
     -- Dermoid/epidermoid tumors
     -- Infectious disease (e.g. brain abscess, cisticercosis, etc.)
     -- Venous angiomas
     -- Subacute/chronic ischemia
     -- Encephalitis
     -- Multiple sclerosis (acute and chronic)
     -- Optic neuritis
     -- Chordomas
     -- Von Hippel Lindau syndrome
     -- Hypertensive leukoencephalopathy.
    - Receipt of any contrast agent < 72 h prior to the study MRIs, or planned receipt of any contrast agent within 72 h after the second study MRI.
    - Planned or expected biopsy in the region of interest or any interventional therapeutic procedure from the first study MRI up to 24 h after the second study MRI.
    - Planned or expected change in any treatment or procedure between the two study MRIs that may alter image comparability and /or chemotherapy which is changed between the two MRI procedures.
    - Contraindications to the administration of gadobutrol, as specified in the local product label.

Trial summary

Enrollment Goal
57
Trial Dates
November 2020 - September 2022
Phase
Phase 2
Could I Receive a placebo
No
Products
Gadoquatrane (BAY1747846)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Universitätsklinikum EssenEssen, 45147, Germany
Completed
University of Iowa Hospitals & ClinicsIowa City, 52242-1089, United States
Withdrawn
Massachusetts General HospitalBoston, 02114-2696, United States
Withdrawn
Universitätsklinikum Schleswig-Holstein (UKSH)Kiel, 24105, Germany
Withdrawn
University of WashingtonSeattle, 98104, United States
Withdrawn
Cedars- Sinai Medical CenterLos Angeles, 90048-0750, United States
Completed
Hokkaido University HospitalSapporo, 060-8648, Japan
Withdrawn
National Hospital Organization Osaka National HospitalOsaka, 540-0006, Japan
Completed
Kishiwada Tokushukai HospitalKishiwada, 596-0042, Japan
Completed
National Hospital Organization Himeji Medical CenterHimeji, 670-8520, Japan
Withdrawn
Osaka International Cancer InstituteOsaka, 541-8567, Japan
Completed
Hiroshima City Hiroshima Citizens HospitalHiroshima, 730-8518, Japan
Completed
Hyogo Prefectural Nishinomiya HospitalNishinomiya, 662-0918, Japan
Completed
MVZ Prof. Uhlenbrock und PartnerDortmund, 44263, Germany
Completed
Northwestern UniversityChicago, 60611, United States
Withdrawn
Charité Campus Benjamin Franklin (CBF)Berlin, 12203, Germany
Withdrawn
Universität Rostock - Medizinische FakultätRostock, 18057, Germany
Completed
Penn State Milton S. Hershey Medical CenterHershey, 17033, United States
Completed
Friedrich-Schiller-Uni. JenaJena, 07740, Germany
Withdrawn
Washington University School of MedicineSaint Louis, 63110, United States
Completed
Social Medical Corporation the Chiyukai foundation Fukuoka Wajiro HospitalFukuoka, 811-0213, Japan
Withdrawn
Med. Fakultät der Martin-Luther-Universität Halle-WittenbergHalle (Saale), 06097, Germany
Completed
National Hospital Organization Kanmon Medical CenterShimonoseki, 752-8510, Japan
Completed
National Hospital Organization Kyushu Medical CenterFukuoka, 810-8563, Japan
Withdrawn
Universitätsklinikum Münster (UKM)Münster, 48149, Germany
Completed
UMHAT Sveti GeorgiPlovdiv, 4002, Bulgaria
Completed
Acibadem City Clinic Multiprofile Hospital for Active TreatmSofia, 1407, Bulgaria
Completed
University Multiprofile Hosp. for Active Treat. Sveti IvanSofia, 1431, Bulgaria

Primary Outcome

  • Overall diagnostic preference
    Overall diagnostic preference using a matched pairs approach was evaluated by 3 blinded readers using an ordinal 5-point scale (greatly prefer gadoquatrane, prefer gadoquatrane, no preference, prefer gadobutrol, greatly prefer gadobutrol). Percentage of participants and the respective Wald confidence intervals (CI) for image preference were reported for each of the 3 readers based on the 3-point preference scale (1=greatly prefer/prefer gadoquatrane, 0=no preference, -1=greatly prefer/prefer gadobutrol). If 2 or 3 readers reach the same conclusion on the recommended action (e.g. no dose adjustment needed), then this will be the recommended action taken.
    date_rangeTime Frame:
    At 5 minute post each injection

Secondary Outcome

  • Sum of lesion visualization parameters on post-contrast images
    The 3 lesion visualization parameters (border delineation/degree of contrast enhancement/internal morphology) were combined by adding them up for each participant and each blinded reader, leading to only one variable on an ordinal 11-point scale (the higher values represent a better lesion visualization). Average reader was the mean of the 3 blinded readers averages of the scores per participant. Lesion border delineation: measured on a 4-point scale (1=None [no/unclear delineation of the lesion boundaries] to 4=Excellent [clear and complete delineation]). Degree of lesion contrast enhancement: measured on a 4-point scale (1=No [lesion is not enhanced] to 4=Excellent [lesion is clearly and brightly enhanced]). Lesion internal morphology: measured on a 3-point scale (1=Poor [structure and internal morphology of the lesion is poorly visible] to 3=Good [structure and internal morphology of the lesion is sufficiently visible]).
    date_rangeTime Frame:
    At 5 minute post each injection
  • Lesion visualization parameter border delineation on pre-contrast and combined pre- and post-contrast images
    Lesion border delineation: up to 5 of the largest lesions were selected and scored using a 4-point scale (1=None [no/unclear delineation of the lesion boundaries] to 4=Excellent [clear and complete delineation]; the higher values represent a better lesion border delineation). Average reader was the mean of the 3 blinded readers averages of the scores per participant.
    date_rangeTime Frame:
    At pre-injection and 5 minute post each injection
  • Lesion visualization parameter contrast enhancement on pre-contrast and combined pre- and post-contrast images
    Degree of lesion contrast enhancement: up to the 5 largest lesions were selected and scored using a 4-point scale (1=No [lesion is not enhanced] to 4=Excellent [lesion is clearly and brightly enhanced]; the higher values represent a better degree of lesion contrast enhancement). Average reader was the mean of the 3 blinded readers averages of the scores per participant.
    date_rangeTime Frame:
    At pre-injection and 5 minute post each injection
  • Lesion visualization parameter internal morphology on pre-contrast and combined pre- and post-contrast images
    Lesion internal morphology: up to 5 of the largest lesions were selected and scored using a 3-point scale (1=Poor [structure and internal morphology of the lesion is poorly visible] to 3=Good [structure and internal morphology of the lesion is sufficiently visible]; the higher values represent a better lesion internal morphology). Average reader was the mean of the 3 blinded readers averages of the scores per participant.
    date_rangeTime Frame:
    At pre-injection and 5 minute post each injection
  • Number of lesions on pre-contrast and combined pre- and post-contrast images
    The 3 blinded readers recorded the total number of lesions for each pre-contrast and combined pre- and post-contrast magnetic resonance image set separately. The numbers of participants by number of detected lesions were reported.
    date_rangeTime Frame:
    At pre-injection and 5 minute post injection

Trial design

Multicenter, single-blind, adaptive dose finding study of single intravenous injections of BAY 1747846 with corresponding blinded read in adult participants with known or highly suspected CNS lesions referred for contrast-enhanced MRI of the CNS
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Diagnostic
Allocation
N/A
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
1

Additional Information

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