Pilot Study of Liver Fibrosis Stage Assessment by Fibroblast Activation Protein Imaging in Patients With Biopsy for Suspected or Proven Nonalcoholic Steatohepatitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CHRU De Nancy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Digestive System Diseases [C06]

Trial duration

3 Jun 2025 → ongoing

Decision date (initial)

2025-03-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

Démontrer que l’intensité de la captation de 68Ga-FAPI-46, mesurée en TEP/TDM au niveau de sites hépatiques biopsiés, est différente en fonction de quatre groupes de fibrose, définis à partir des analyses des prélèvements biopsiques (stade 4 : cirrhose, stade 3 : septa fibreux, stade 2 : fibrose portale et périsinusoïdale, et stade <2 : fibrose périsinusoïdale ou périportale, ou fibrose absente (Kleiner, 2005)).

Secondary objectives 5

1. 1. Déterminer les valeurs seuils d’intensité de captation hépatique du 68Ga-FAPI-46 en TEP/TDM associées à chacun des quatre groupes de stades histologiques de fibrose (stades 4, 3, 2 et < 2).
2. 2. Describe the topographical distribution of hepatic 68Ga-FAPI-46 uptake intensity on PET/CT throughout the liver volume.
3. 3. Describe 68Ga-FAPI-46 uptake in the entire imaged volume (whole-body PET/CT), and in particular sites where uptake appears excessive (possible foci of fibrosis, inflammation, cancer).
4. 4. Estimate inter- and intra-observer reproducibility of 68Ga-FAPI-46 hepatic uptake intensity measurements used to address the primary objective.
5. 5. Evaluate the specific contribution of 68Ga-FAPI-46 PET/CT in characterizing the stage of hepatic fibrosis, in addition to the usual clinico-biological scores (CBC, FIB-4, Fibrometer) and pulse elastometry (Fibroscan®).

Conditions and MedDRA coding

non-alcoholic hepatic steatosisalcoholic hepatic steatosis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Individuals with recent liver biopsy for suspected or confirmed NASH
2. NASH 2. Individuals of legal age, who have received full information on the organization of the research and have signed an informed consent form.
3. 3. Person, affiliated to a social security scheme or beneficiary of such a scheme.
4. 4. Person who has undergone a preliminary clinical examination appropriate to the research.
5. 5. Histological 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 12

1. 1. Known hypersensitivity to 68Ga-FAPI-46 or to any of the excipients or components of the radiopharmaceutical.
2. 2. Infection with HCV/HBV.
3. 3. Decompensated cirrhosis (ascites, hepatic insufficiency, hepatorenal syndrome, etc.).
4. 4. Known hepatocellular carcinoma.
5. 5. Steatogenic treatment (corticosteroid, Tamoxifen, Amiodarone, Methotrexate).
6. 6. Excessive alcohol consumption in the last 5 years (>210 g/week in men, >140 g/week in women).
7. 7. Clinically unstable state not suitable for 68Ga-FAPI-46 PET/CT scan.
8. 8. Women of childbearing age without effective contraception.
9. 9. Pregnant or breast-feeding mother.
10. 10. Persons covered by articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code.
11. 11. Persons deprived of their liberty by judicial or administrative decision, persons under psychiatric care pursuant to articles L. 3212-1 and L. 3213-1.
12. 12. Persons covered by articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 6

1. 1. SUV threshold values associated with each of the four fibrosis histological stage groups (stages 4, 3, 2 and < 2) by the naive Bayes classifier.
2. 2. Location 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).
3. 3. Search, 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).
4. 4. Intra-class correlation coefficients and their 95% confidence intervals.
5. 5. Variation 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®).
6. 6. Identical 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

Sponsor organisation

CHRU De Nancy

Address

Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034

City

Nancy Cedex

Postcode

54035

Country

France

Scientific contact point

Organisation

CHRU De Nancy

Contact name

CHEVALIER

Public contact point

Organisation

CHRU De Nancy

Contact name

CHEVALIER

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications