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

Central Nervous System Pathology Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04307186
• Other study ID #: 20241
• Secondary ID: 2019-001560-30
• Status: Completed
• Phase: Phase 2
• Start date: November 18, 2020
• Est. completion date: September 6, 2022

Study information

• Verified date: October 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: September 6, 2022
• Est. primary completion date: September 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Central Nervous System Pathology

Intervention

Drug:
• Gadoquatrane (BAY1747846)
Solution for IV injection, single dose
• Gadobutrol (Gadovist/Gadavist)
Solution for IV injection, single dose

Locations

Country	Name	City	State
Bulgaria	UMHAT Sveti Georgi	Plovdiv
Bulgaria	Acibadem City Clinic Multiprofile Hospital for Active Treatm	Sofia
Bulgaria	University Multiprofile Hosp. for Active Treat. Sveti Ivan	Sofia
Germany	MVZ Prof. Uhlenbrock und Partner	Dortmund	Nordrhein-Westfalen
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Friedrich-Schiller-Uni. Jena	Jena	Thüringen
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	Social Medical Corporation the Chiyukai foundation Fukuoka Wajiro Hospital	Fukuoka
Japan	National Hospital Organization Himeji Medical Center	Himeji	Hyogo
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima
Japan	Kishiwada Tokushukai Hospital	Kishiwada	Osaka
Japan	Hyogo Prefectural Nishinomiya Hospital	Nishinomiya	Hyogo
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	National Hospital Organization Kanmon Medical Center	Shimonoseki	Yamaguchi
United States	Northwestern University	Chicago	Illinois
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Bulgaria,  Germany,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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