(S)-2,2',2''-(10-(2-(4-(3-((4-(2-(2-CYANO-4,4-DIFLUOROPYRROLIDIN-1-YL)-2-OXOETHYLCARBAMOYL)-QUINOLIN-6-YL)(METHYL)AMINO)-PROPYL)PIPERAZIN-1-YL)-2-OXOETHYL)-68GA-[1,4,7,10]-TETRAAZACYCLODODECANE-1,4,7-TRIYL)TRIACETATE for Nonalcoholic steatohepatitis (NASH) | Liver fibrosis

Inclusion criteria

• {"criterion_text":"- 1.\tIndividuals with recent liver biopsy for suspected or confirmed NASH\n- NASH 2.\tIndividuals of legal age, who have received full information on the organization of the research and have signed an informed consent form.\n- 3.\tPerson, affiliated to a social security scheme or beneficiary of such a scheme.\n- 4.\tPerson who has undergone a preliminary clinical examination appropriate to the research.\n- 5.\tHistological stage of fibrosis obtained at biopsy in accordance with the planned numbers (an equivalent number of patients with histological stages >2 and ≤ 2 must be recruited in each center, and a number of at least 16 patients must be included by all centers in each of the 4 groups of histological stages of fibrosis)."}

Exclusion criteria

• {"criterion_text":"- 1.\tKnown hypersensitivity to 68Ga-FAPI-46 or to any of the excipients or components of the radiopharmaceutical.\n- 10.\tPersons covered by articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code.\n- 11.\tPersons deprived of their liberty by judicial or administrative decision, persons under psychiatric care pursuant to articles L. 3212-1 and L. 3213-1.\n- 12.\tPersons covered by articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code.\n- 2.\tInfection with HCV/HBV.\n- 3.\tDecompensated cirrhosis (ascites, hepatic insufficiency, hepatorenal syndrome, etc.).\n- 4.\tKnown hepatocellular carcinoma.\n- 5.\tSteatogenic treatment (corticosteroid, Tamoxifen, Amiodarone, Methotrexate).\n- 6.\tExcessive alcohol consumption in the last 5 years (>210 g/week in men, >140 g/week in women).\n- 7.\tClinically unstable state not suitable for 68Ga-FAPI-46 PET/CT scan.\n- 8.\tWomen of childbearing age without effective contraception.\n- 9.\tPregnant or breast-feeding mother."}

Primary endpoints

• {"endpoint_text":"- Measurement of 68Ga-FAPI-46 uptake intensity, with Standardized Uptake Values maximum (SUVmax), average (SUVmean) and peak (SUVpeak), in areas centered on biopsy sites, the reference then being a classification of fibrosis stages determined by centralized biopsy rereading (stages 4, 3, 2 and < 2 (Kleiner, 2005; Bedossa, 2012).","definition_or_measurement_approach":"Measurement of 68Ga-FAPI-46 uptake intensity using SUVmax, SUVmean and SUVpeak in regions centered on biopsy sites; reference standard is centralized biopsy rereading with fibrosis stages (4, 3, 2, <2) per Kleiner 2005 / Bedossa 2012."}

Secondary endpoints

• {"endpoint_text":"- 1.\tSUV threshold values associated with each of the four fibrosis histological stage groups (stages 4, 3, 2 and < 2) by the naive Bayes classifier.","definition_or_measurement_approach":"Derive SUV threshold values for each fibrosis stage group using a naive Bayes classifier applied to PET/CT SUV measurements."}
• {"endpoint_text":"- 2.\tLocation of the uptake zone with maximum activity (SUVmax and SUVPIC zones, respectively), and of the homogeneity of SUV distribution over the liver volume (histogram of liver voxels per SUV value category).","definition_or_measurement_approach":"Identify location of maximum uptake zones (SUVmax, SUVPIC) and assess homogeneity via histogram of liver voxels by SUV categories across the liver volume on PET/CT."}
• {"endpoint_text":"- 3.\tSearch, on whole-body images, for 68Ga-FAPI-46 uptake foci located outside the tracer's normal elimination zones (urinary excretory tracts), and which may correspond to abnormal areas of fibrosis and/or inflammation, or even cancer (this new tracer has already demonstrated a good ability to detect many cancers).","definition_or_measurement_approach":"Whole-body PET/CT review to identify extra-hepatic foci of 68Ga-FAPI-46 uptake outside normal elimination zones that may represent fibrosis, inflammation or malignancy."}
• {"endpoint_text":"- 4.\tIntra-class correlation coefficients and their 95% confidence intervals.","definition_or_measurement_approach":"Calculate intra-class correlation coefficients (and 95% CIs) to evaluate inter- and intra-observer reproducibility of hepatic uptake intensity measurements."}
• {"endpoint_text":"- 5.\tVariation in the degree of prediction of the four groups of histological stages of fibrosis when the 68Ga-FAPI-46 PET/CT variables are added to the variables derived from the usual clinico-biological scores (CBC, FIB-4, Fibrometer) and pulse elastometry (Fibroscan®).","definition_or_measurement_approach":"Assess incremental predictive value of PET/CT variables added to clinico-biological scores and Fibroscan using comparative prediction metrics."}
• {"endpoint_text":"- 6.\tIdentical to the main objective, the reference being the histological fibrosis score determined in the SAF score, and patients being grouped into quartiles according to this score.","definition_or_measurement_approach":"Repeat primary objective analyses using SAF histological fibrosis score grouped into quartiles as the reference standard."}

France

Earliest CTIS Part Ii Submission Date

03-03-2025

Latest Decision Or Authorization Date

10-03-2025

Processing Time Days

7

Number Of Sites

1

Number Of Participants

72

Primary sponsor

Full Name

CHRU De Nancy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France