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

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

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.

Study Overview

• Status: Completed
• Conditions: Central Nervous System Pathology
• Intervention / Treatment: Drug: Gadobutrol (Gadovist/Gadavist); Drug: Gadoquatrane (BAY1747846)

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sveti Georgi
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Multiprofile Hospital for Active Treatm
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hosp. for Active Treat. Sveti Ivan
• Germany
  • Nordrhein-Westfalen
    • Dortmund, Nordrhein-Westfalen, Germany, 44263
      • MVZ Prof. Uhlenbrock und Partner
    • Essen, Nordrhein-Westfalen, Germany, 45147
      • Universitätsklinikum Essen
  • Thüringen
    • Jena, Thüringen, Germany, 07740
      • Friedrich-Schiller-Uni. Jena
• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan, 811-0213
    • Social Medical Corporation the Chiyukai foundation Fukuoka Wajiro Hospital
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hiroshima Citizens Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Hyogo
    • Himeji, Hyogo, Japan, 670-8520
      • National Hospital Organization Himeji Medical Center
    • Nishinomiya, Hyogo, Japan, 662-0918
      • Hyogo Prefectural Nishinomiya Hospital
  • Osaka
    • Kishiwada, Osaka, Japan, 596-0042
      • Kishiwada Tokushukai Hospital
  • Yamaguchi
    • Shimonoseki, Yamaguchi, Japan, 752-8510
      • National Hospital Organization Kanmon Medical Center
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242-1089
      • University of Iowa Hospitals & Clinics
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gadobutrol + Gadoquatrane; Participants will receive one intravenous (IV) injection of gadobutrol 0.1 millimole(s) gadolinium/kilogram body weight (mmol Gd/kg bw) and one IV injection of Gadoquatrane (BAY1747846).	Drug: Gadobutrol (Gadovist/Gadavist); Solution for IV injection, single dose; Drug: Gadoquatrane (BAY1747846); Solution for IV injection, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 5 minute post each injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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]).	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.	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.	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.	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.	At pre-injection and 5 minute post injection

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2020
• Primary Completion (Actual): September 5, 2022
• Study Completion (Actual): September 6, 2022

Study Registration Dates

• First Submitted: March 11, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: CNS
• Other Study ID Numbers: 20241; 2019-001560-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No