GDX-44-014 - GDX-101 study was conducted in Japan including 2 cohorts (adult cohort for adult population and pediatric cohort for pediatric population), with different designs: * The adult cohort had a prospective, multi-center, randomized, double-blind, controlled, and cross-over design. * The pediatric cohort had a prospective, multi-center, non-randomized, open-label and single arm design. The primary objective was to demonstrate the non-inferiority of gadopiclenol-enhanced MRI at 0.05 mmol/kg body weight (BW) compared to gadobutrol-enhanced MRI at 0.1 mmol/kg BW in terms of lesion visualization for adult patients referred for contrast-enhanced MRI of Central Nervous System (CNS) or Body regions.
Adult cohort: The trial included a maximum of 5 visits and the record of patient's diagnosis as standard of truth: * One screening visit (V1) up to 7 days prior to the imaging visit (V2) (V1 could be done on the same day as V2 if all the inclusion/non-inclusion criteria were met). * Two sequential imaging visits (V2 and V4, minimum interval 2 days and up to 14 days): each visit consisted of gadopiclenol injection or comparator injection and MRI procedure. * Two safety visits (V3 and V5): 1 day after each injection and MRI examination. Pediatric cohort: The inclusions was divided into 4 age groups: patients from birth to 23 months of age inclusive, patients from 2 to 6 years, patients from 7 to 11 years and patients from 12 to 17 years. The recruitment in the 3 older groups of pediatric patients could be conducted in parallel with adult patients' enrolment. The decision to start the inclusion in the group of patients aged from birth to 23 months was taken by the Trial Safety Review Board (TSRB). The trial included a maximum of 3 visits and the record of patient's diagnosis as standard of truth: * One screening visit (V1) up to 7 days prior to the imaging visit (V2) (V1 could be done on the same day as V2 if all the inclusion/non-inclusion criteria were met). * One imaging visit (V2) consisted of gadopiclenol injection and MRI procedure. * pharmacokinetics (PK) group: Blood sampling for PK started after gadopiclenol injection according to defined blood sampling schedule and took up to 8 hours. * One safety visit (V3): 1 day after gadopiclenol injection and MRI examination. All Patients: Images were assessed off-site in a centralized manner. Pediatric group for pharmacokinetics (PK) analysis : Up to 24 patients of the pediatric cohort would be included in gadopiclenol PK profile assessment. The approach implemented for PK analyses allowed sparse blood sampling only and was selected to minimize the clinical burden to children. All cohorts : During the trial, the safety of the patients was monitored and assessed based on the reporting of adverse events (AEs), including vital signs, ECG for pediatric patients and clinical laboratory parameters (blood samples).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
QUADRUPLE
Enrollment
240
Dose/volume: Gadopiclenol administered was calculated based on patient's weight at the dose of 0.05 mmol/kg BW
Dose/volume of comparator: Gadobutrol administered was calculated based on patient's weight at the dose of 0.1 mmol/kg BW.
Meitetsu Hospital
Aichi, Japan
Fukuoka University Hospital
Fukuoka, Japan
Gifu University Hospital
Gifu, Japan
Gunma University Hospital
Gunma, Japan
Hiroshima City Hiroshima Citizens Hospital
Hiroshima, Japan
Nakamura Memorial Hospital
Hokkaido, Japan
National Hospital Organization Shikoku Medical Center for Children and Adults
Kagawa, Japan
Kanagawa Children's Medical Center
Kanagawa, Japan
Kobe City Medical Center General Hospital
Kobe, Japan
University Hospital, Kyoto Prefectural University of Medicine
Kyoto, Japan
...and 17 more locations
Lesion Visualization on Paired Images: Border Delineation
The lesion visualization criterion (per patient) was based on 3 co-primary criteria (border delineation, internal morphology and degree of contrast enhancement) assessed by 3 independent off-site blinded readers. The IBR recorded each of the 3 co-primary criteria for up to 10 largest and most enhancing lesions on Paired (pre+post) images performed with gadopiclenol and Paired (pre+post) images performed with gadobutrol. Delineation of the lesion border was defined as the distinction of lesion from surrounding tissues, structures, or edema, and the detection of extent of the lesion. This criterion was assessed through the following scale: 1. = None 2. = Moderate 3. = Good 4. = Excellent: For this co-primary criterion, a mean of scores for each patient and for each reader was calculated and ranged from 1 to 4.
Time frame: At each MRI exam: the first MRI at Day 1 and the second MRI performed after a wash out period of 2 to 14 days (adult cohort)
Lesion Visualization on Paired Images: Internal Morphology
The lesion visualization criterion (per patient) was based on 3 co-primary criteria (border delineation, internal morphology and degree of contrast enhancement) assessed by 3 independent off-site blinded readers. The IBR recorded each of the 3 co-primary criteria for up to 10 largest and most enhancing lesions on Paired (pre+post) images performed with gadopiclenol and Paired (pre+post) images performed with gadobutrol. Internal morphology of the lesion included an identification of lesion architecture and the intra-lesion features such as necrosis, hemorrhage, and vascularity. This criterion was assessed through the following scale: 1. = Poor 2. = Moderate 3. = Good 4. = Excellent For this co-primary criterion "internal morphology", a mean of scores for each patient and for each reader was calculated and ranged from 1 to 4.
Time frame: At each MRI exam: the first MRI at Day 1 and the second MRI performed after a wash out period of 2 to 14 days (adult cohort)
Lesion Visualization on Paired Images: Degree of Contrast Enhancement
The lesion visualization criterion (per patient) was based on 3 co-primary criteria (border delineation, internal morphology and degree of contrast enhancement) assessed by 3 independent off-site blinded readers. The IBR recorded each of the 3 co-primary criteria for up to 10 largest and most enhancing lesions on Paired (pre+post) images performed with gadopiclenol and Paired (pre+post) images performed with gadobutrol. The criterion "degree of contrast enhancement" was a qualitative assessment (not based on signal intensity measurement) according to the following scale: 1. = No: no enhancement 2. = Moderate: weakly enhanced 3. = Good: clearly enhanced 4. = Excellent: clearly and brightly enhanced For each co-primary criterion, a mean of scores for each patient and for each reader was calculated and ranged from 1 to 4.
Time frame: At each MRI exam: the first MRI at Day 1 and the second MRI performed after a wash out period of 2 to 14 days (adult cohort)
Pediatric Cohort: Lesion Visualization on Paired Images Compared With Pre Images: Border Delineation
The lesion visualization criterion based on 3 co-criteria: border delineation, internal morphology and degree of contrast enhancement assessed on the images acquired during the MRI performed with gadopiclenol assessed by 3 independent off-site blinded readers (IBR). The IBR recorded each of the 3 co-criteria for up to 10 largest and most enhancing lesions on Paired (pre+post) images and Pre images performed with gadopiclenol as contrast agent. Definitions of each co-criteria and score calculation were provided in the section for primary outcome measure.
Time frame: At MRI exam, Day 1 (pediatric cohort)
Pediatric Cohort: Lesion Visualization on Paired Images Compared With Pre Images: Internal Morphology
The lesion visualization criterion based on 3 co-criteria: border delineation, internal morphology and degree of contrast enhancement assessed on the images acquired during the MRI performed with gadopiclenol assessed by 3 independent off-site blinded readers (IBR). The IBR recorded each of the 3 co-criteria for up to 10 largest and most enhancing lesions on Paired (pre+post) images and Pre images performed with gadopiclenol. Definitions of each co-criteria and score calculation were provided in the section for primary outcome measure.
Time frame: At MRI exam, Day 1 (pediatric cohort)
Pediatric Cohort: Lesion Visualization on Paired Images Compared With Pre Images: Degree of Contrast Enhancement
The lesion visualization criterion based on 3 co-criteria: border delineation, internal morphology and degree of contrast enhancement assessed on the images acquired during the MRI performed with gadopiclenol assessed by 3 independent off-site blinded readers (IBR). The IBR recorded each of the 3 co-criteria for up to 10 largest and most enhancing lesions on Paired (pre+post) images and Pre images performed with gadopiclenol. Definitions of each co-criteria and score calculation were provided in the section for primary outcome measure.
Time frame: At MRI exam, day 1 (pediatric cohort)
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