Exploratory Study Evaluating the Relevance of [68Ga]Ga-FAPI-46 for Staging and Identifying Progressing Patients With Transthyretin Cardiac Amyloidosis (FAPICAM)

Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy caused by amyloid fibril deposition, leading to heart failure and arrhythmias. Despite advances in diagnosis, the disease remains commonly unrecognized and presents heterogeneously. Recent therapies targeting transthyretin stabilization and gene silencing have improved outcomes, but current staging systems based on biological and functional markers have limited ability to guide treatment.

Imaging techniques such as cardiac magnetic resonance (CMR) provide tissue characterization, but noninvasive molecular imaging of myocardial fibrotic activity remains limited. Positron emission tomography (PET) tracers targeting fibroblast activation protein (FAPI), labeled with gallium-68 (68Ga), offer a promising approach to detect and quantify fibroblast activity associated with myocardial remodeling.

This study aims to evaluate [68Ga]Ga-FAPI PET imaging for staging ATTR-CM and distinguishing patients with disease progression under therapy. The investigators hypothesize that [68Ga]Ga-FAPI uptake reflects fibrotic activity correlating with disease severity and progression. If validated, [68Ga]Ga-FAPI PET could serve as a novel biomarker for improved staging and personalized strategies in ATTR-CM.

Study Overview

• Status: Not yet recruiting
• Conditions: Transthyretin Cardiac Amyloidosis
• Intervention / Treatment: Drug: [68Ga]Ga-FAPI-46

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Thomas EUGENE, MD; Phone Number: +33 02 40 08 41 36; Email: Thomas.EUGENE@chu-nantes.fr
• Study Contact Backup: Name: Nicolas PIRIOU, MD; Email: Nicolas.PIRIOU@chu-nantes.fr

Study Locations

• France
  • Nantes, France, 44093
    • CHU Nantes
    • Principal Investigator: Nicolas PIRIOU, MD
    • Contact: Faustine LELAN, PhD; Phone Number: +33 0276643491; Email: faustine.lelan@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women ≥ 18 years
• Definite ATTR-CM diagnosis based on the 2021 ESC expert consensus
• Written and signed informed consent (obtained on the screening day at the latest and before any investigation)
• Affiliation with French social security system or beneficiary from such system

• Women must meet one of the following criteria at the time of inclusion:

  • present a negative pregnancy test (blood test) before the injection of [68Ga]Ga-FAPI-46 and use highly1 effective contraceptive measures for a duration of 6 months after the PET with [68Ga]Ga-FAPI-46;
  • or be post-menopausal (aged over 50 with amenorrhea for at least 12 months after stopping all exogenous hormone treatments);
  • or (if under 50 years of age) have been in amenorrhea for at least 12 months after stopping exogenous hormone treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels corresponding to post-menopausal levels;
  • or have undergone irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (this operation must be documented);
• Male patients will be required to use male contraception (condoms) for a duration of 3 months after the PET;
• Women partners will be required to use an acceptable2 contraceptive measure (as they will not receive the trial drug) for a duration of 3 months after the PET;
• Male partners will be required to use male contraception (condoms) for a duration of 6 months after the PET.

Exclusion Criteria:

• History of Myocardial infarction or myocarditis
• Severe aortic stenosis
• Current or prior participation in a clinical trial evaluating a TTR-targeted gene-silencing therapy (TTR= transthyretin) or an amyloid-depleting treatment for cardiac transthyretin amyloidosis (ATTR-CM).
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Women who are pregnant or breastfeeding. A serum pregnancy test will be performed at the start of the study and within 48 hours prior to PET for all female subjects of childbearing potential.
• Patient under guardianship or trusteeship.
• Patient under judicial protection.
• Patient unable to understand spoken or written French
• Known hypersensitivity to gallium-68, to any excipient or derivative

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: [68Ga]Ga-FAPI-46 PET; [68Ga]Ga-FAPI-46 PET acquisition at approximatively 40 min after the injection over 20-45 minutes. The PET imaging will be associated with either MRI (magnetic resonance imaging) or CT (computed tomography) at the investigator's discretion.	Drug: [68Ga]Ga-FAPI-46; [68Ga]Ga-FAPI-46 PET acquisition at approximatively 40 min after the injection over 20-45 minutes. The PET imaging will be associated with either MRI or CT at the investigator's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of quantitative evaluation of [68Ga]Ga-FAPI-46 cardiac uptake	Comparison of quantitative evaluation of [68Ga]Ga-FAPI-46 cardiac uptake (SUV (Standard Uptake Value) Ratio : left ventricular myocardial SUV to blood pool SUV) among the different Columbia ATTR-CM stages (1-3 points ; 4-6 points ; 7-9 points) in order to characterize the contribution of [68Ga]Ga-FAPI-46 PET imaging in evaluating the severity of transthyretin amyloid cardiomyopathy (ATTR-CM).	within 30 days

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: FAPI-46; staging and identifying progressing patients
• Other Study ID Numbers: RC25_0276; 2025-523616-36-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No