Clinical trial NCT05915728: A Study to Compare How Well Gadoquatrane Works and Its Safety With an Already Available Contrast Agent for MRI in People With Any Known or Suspected Problems of the Body (Except 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 Any Body Region (Except 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
Non-central Nervous System Pathology
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2023-06-23
Enrollment: 404
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The site staff in charge of the preparation and administration of study intervention will be unblinded and will not be involved in any evaluation of safety and efficacy. The site staff in charge of conducting all other study procedures as per the schedule of activities (SoA) will remain blinded to the study intervention administered.
Primary purpose: DIAGNOSTIC

Brief summary: Researchers are looking for a better way to help people with any known or suspected problems (except 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 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 known or suspected problems (except brain or spinal cord-related problems) with 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 magnetic resonance angiography \[MRA\]), 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, with known or suspected pathology of any body region, e.g. head and neck (except central nervous system \[CNS\]), thorax (including e.g. breast, heart, chest wall), abdomen (including e.g. liver, kidney, pancreas), pelvis (including e.g. prostate, uterus, ovaries), extremities (including upper and lower.
* 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
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: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Indian Wells
country: United States
facility: Halo Diagnostics - Indian Wells
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Miami
country: United States
facility: Biogenix Molecular, LLC
state: Florida
city: Columbia
country: United States
facility: University of Missouri Hospital and Clinic - Neuroradiology
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: Pennsylvania State University College of Medicine
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Hospital - Cardiology
state: Texas
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: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Dr Georgi Stranski Pleven | Surgery Department
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 | University Multiprofile Hospital for Active Treatment Tokuda - Radiology Department
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: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
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 Hospital
state: Beijing
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: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
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
country: Czechia
facility: Fakultní nemocnice Ostrava - Radiodiagnostický ústav
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnice
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen - Lochotin
city: Praha 2
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
city: Praha 4 - Krc
country: Czechia
facility: Fakultní Thomayerova nemocnice - klinicko-farmakologická jednotka
city: Angers
country: France
facility: Centre Hospitalier Universitaire - Angers
city: Bron
country: France
facility: Hospices Civils de LYON
city: Dijon
country: France
facility: Centre Hospitalier Universitaire de Dijon
city: Paris
country: France
facility: Hôpital Bichat Claude Bernard - Service de radiologie
city: Freiburg
country: Germany
facility: Uniklinik Freiburg / Radiologie
state: Baden-Württemberg
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen - Institut für Diagnostische und Interventionelle Radiologie
state: Niedersachsen
city: Bonn
country: Germany
facility: Uniklinik Bonn / Radiologie
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Helios Herzzentrum Leipzig - Abteilung für Radiologie
state: Sachsen
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch - Klinik für Kardiologie - Kardio MRT
city: Essen
country: Germany
facility: Universitätsklinikum Essen - Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie - 21197
city: Debrecen
country: Hungary
facility: Debreceni Egyetem - Klinikai Kozpont - Onkologiai Klinika
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Szeged
country: Hungary
facility: Trial Pharma Kft. Szeged
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliero-Universitaria Sant'Andrea - UOC Radiologia
state: Lazio
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia - Radiologia Diagnostica 1
state: Lombardia
city: Treviso
country: Italy
facility: AULSS N. 2 Marca Trevigiana_Ospedale di Treviso - UOC Radiologia
state: Veneto
city: Kitakyushu
country: Japan
facility: JCHO Kyushu Hospital
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Hospital of the University of Occupational and Environmental Health, Japan
state: Fukuoka
city: Hakodate
country: Japan
facility: Hakodate Central General Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Nishinomiya
country: Japan
facility: Hyogo Prefectural Nishinomiya Hospital
state: Hyogo
city: Hakusan
country: Japan
facility: Public Central Hospital of Matto Ishikawa | Clinical Trial Management Office
state: Ishikawa
city: Kanazawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center | Clinical Trial Management Office
state: Ishikawa
city: Takamatsu
country: Japan
facility: Takamatsu Red Cross Hospital
state: Kagawa
city: Kishiwada
country: Japan
facility: Kishiwada Tokushukai Hospital
state: Osaka
city: Yonago
country: Japan
facility: Japan Organization of Occupational Health and Safety Sanin Rosai Hospital
state: Tottori
city: Shimonoseki
country: Japan
facility: National Hospital Organization Kanmon Medical Center
state: Yamaguchi
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: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Bialystok
country: Poland
facility: NZOZ Kendron
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Centra Medyczne Medyceusz
city: Warszawa
country: Poland
facility: Centrum Medycznym Gamma
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge Radiology
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
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: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
Study officials:
References: