Contrast Enhancement in Magnetic Resonance Imaging Clinical Trial
— Quanti CNSOfficial 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 the Central Nervous System (CNS), Compared to 0.1 mmol Gd/kg Approved Macrocyclic Gadolinium-based Contrast Agents (GBCAs)
| Verified date | June 2024 |
| Source | Bayer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 303 |
| Est. completion date | May 31, 2024 |
| Est. primary completion date | May 30, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 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) 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) |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Centro de Diagnóstico Dr. Enrique Rossi | Buenos Aires | Ciudad Auton. De Buenos Aires |
| Argentina | Sanatorio Otamendi | Imaging Diagnostic Center | Buenos Aires | Ciudad Auton. De Buenos Aires |
| Argentina | Instituto Alexander Fleming | Sede Central - Departamento de Diagnostico por Imagenes | Caba | Ciudad Auton. De Buenos Aires |
| Argentina | Clinica Universitaria Reina Fabiola | Consultorios Externos | Cordoba | Córdoba |
| Argentina | Sanatorio Allende | Departamento de Investigación Clínica | Córdoba | |
| Argentina | Fundacion Cientifica del Sur | Centro de Lomas de Zamora - Imaging Interventionism Department | Lomas De Zamora, Buenos Aires | Buenos Aires |
| Bulgaria | Multiprofile Hospital for Active Treatment Central Onco Hospital | Independent Medical Diagnostic Laboratory Mediscan | Plovdiv | |
| Bulgaria | University Multiprofile Hospital for Active Treatment Sveti Georgi | Base II - Imaging Diagnostic Department | Plovdiv | |
| Bulgaria | UMHAT Alexandrovska EAD | Sofia | |
| Bulgaria | UMHAT Tsaritsa Joanna-ISUL EAD Sofia | Sofia | |
| Bulgaria | University Multiprofile Hospital for Active Treatment Prof. Dr. Alexander Chirkov EAD | Sofia | |
| Bulgaria | University Multiprofile Hospital for Active Treatment St. Ivan Rilski | Radiology Department | Sofia | |
| Bulgaria | MHAT Sveta Marina EAD | Varna | |
| Canada | London Health Sciences Centre (LHSC) - University Hospital | London | |
| Canada | Hopital du Sacre-Coeur de Montreal | Montreal | Quebec |
| China | Beijing Chaoyang Hospital, Capital Medical University | Beijing | |
| China | Beijing Tiantan Hospital, Captial Medical University | Beijing | |
| China | Peking University First Hospital | Beijing | |
| China | Nanfang Hospital, Southern Medical University | Guangzhou | Guangdong |
| China | Sun Yat-Sen Memorial Hosp. Sun Yat-Sen Univ. | Guangzhou | Guangdong |
| China | The First Affiliated Hospital of Jinan University | Guangzhou | Guangdong |
| China | Huai'an First People's Hospital, Nanjing Medical University | Huai'An | Jiangsu |
| China | Zhongda Hospital Southeast University | Nanjing | Jiangsu |
| China | The First Affiliated Hospital of Wenzhou Medical University | Wenzhou | Zhejiang |
| Czechia | Fakultni nemocnice Brno | Brno | |
| Czechia | Fakultni nemocnice Ostrava | Ostrava | |
| Czechia | Fakultni nemocnice Plzen - Lochotin | Plzen | |
| Czechia | Fakultni Thomayerova Nemocnice | Prague | |
| Czechia | Vseobecna fakultni nemocnice v Praze | Praha 2 | |
| France | Center Hospitalier Michallon - Grenoble | La Tronche | |
| France | Centre Hospitalier Lyon Sud | Pierre Benite | |
| France | CHU STRASBOURG - Hôpital de Hautepierre | Strasbourg Cedex | |
| Germany | Uniklinik Augsburg / Radiologie | Augsburg | Bayern |
| Germany | Universitätsklinikum Essen | Essen | Nordrhein-Westfalen |
| Germany | Uniklinik Kiel /Radiologie und Neuroradiologie | Kiel | Schleswig-Holstein |
| Germany | St. Franziskus-Hospital GmbH | Münster | Nordrhein-Westfalen |
| Hungary | Debreceni Egyetem Klinikai Kozpont, Idegsebeszeti Klinika | Debrecen | |
| Hungary | Szent Damjan Gorogkatolikus Korhaz | Kisvarda | |
| Hungary | Idegsebeszeti Klinika | Pecs | |
| Hungary | Trial Pharma Kft. Szeged | Szeged | |
| Italy | ASL Provincia di Barletta-Andria-Trani | Andria | Puglia |
| Italy | ASST Papa Giovanni XXIII | Bergamo | Lombardia |
| Italy | A.O.U. Sant'Andrea | Roma | Lazio |
| Japan | Shonan Fujisawa Tokushukai Hospital | Fujisawa | Kanagawa |
| Japan | National Hospital Organization Kyushu Medical Center | Fukuoka | |
| Japan | Social Medical Corporation the Chiyukai foundation Fukuoka Wajiro Hospital | Fukuoka | |
| Japan | National Hospital Organization Kanazawa Medical Center | Clinical Trial Management Office | Kanazawa | Ishikawa |
| Japan | Kishiwada Tokushukai Hospital | Kishiwada | Osaka |
| Japan | Kure Kyosai Hospital | Kure | Hiroshima |
| Japan | Japan Organization of Occupational Health and Safety Kagawa Rosai Hospital | Marugame | Kagawa |
| Japan | Hyogo Prefectural Nishinomiya Hospital | Nishinomiya | Hyogo |
| Japan | Osaka City General Hospital | Osaka | |
| Japan | National Hospital Organization Kanmon Medical Center | Shimonoseki | Yamaguchi |
| Korea, Republic of | Inje University Busan Paik Hospital | Busan | |
| Korea, Republic of | Konkuk University Medical Center | Seoul | Seoul Teugbyeolsi |
| Korea, Republic of | Seoul National University Hospital | Seoul | Seoul Teugbyeolsi |
| Sweden | Karolinska University Hospital, Huddinge Neuroradiology | Stockholm | |
| Sweden | Karolinska University Hospital, Solna Neuroradiology | Stockholm | |
| Sweden | Uppsala University Hospital, Neuroradiology Department | Uppsala | |
| Turkey | Hacettepe Universitesi Tip Fakultesi | Ankara | |
| Turkey | Binali Yildirim Universitesi Mengucek Gazi EAH - Radyoloji | Erzincan | |
| Turkey | Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi | Istanbul | |
| Turkey | Istanbul Universitesi Istanbul Tip Fakultesi | Istanbul | |
| Turkey | Koc Universitesi Tip Fakultesi - Radyoloji | Istanbul | |
| Turkey | Ondokuz Mayis Uni Tip Fakultesi | Samsun | |
| United Kingdom | University Hospital of Wales | Cardiff | |
| United Kingdom | Queen Elizabeth University Hospital | Glasgow | Glasgow City |
| United Kingdom | Charing Cross Hospital | London | |
| United States | Northwestern University - Dept. of Radiology | Chicago | Illinois |
| United States | University of Missouri -Radiology - Columbia | Columbia | Missouri |
| United States | Duke University School of Medicine | Durham | North Carolina |
| United States | QUEST Research Institute | Farmington Hills, MI | Farmington Hills | Michigan |
| United States | Halo Diagnostics | Indian Wells | California |
| United States | Biogenix Molecular, LLC | Miami | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Bayer |
United States, Argentina, Bulgaria, Canada, China, Czechia, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Sweden, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | 1 day procedure | |
| Primary | 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 | 1 day procedure | |
| Primary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | 1 day procedure | |
| Secondary | 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 | Within 24 ± 4 hours after administration of gadoquatrane or any approved macrocyclic GBCAs | |
| Secondary | 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 | Within 24 ± 4 hours after administration of gadoquatrane or any approved macrocyclic GBCAs |