Study on the detection of cardiac inflammation by PET-CT imaging with a new tracer called '68Ga-NOTA-Anti-MMR-VHH2' in patients with cardiac sarcoidosis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cliniques Universitaires Saint-Luc

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2024-09-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BioWin

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Safety

Evaluate the ability of in vivo 68Ga-NOTA-Anti-MMR-VHH2 PET/CT imaging to detect cardiac sarcoid lesions in patients with histological or clinical ‘probable’ diagnosis of cardiac sarcoidosis based on the HRS 2014 criteria including a patchy pattern on FDG-PET/CT consistent with cardiac sarcoidosis.

Secondary objectives 5

1. To confirm the safety of 68Ga-NOTA-Anti-MMR-VHH2 (including immunogenicity).
2. To evaluate the potential of 68Ga-NOTA-Anti-MMR-VHH2 PET/CT to detect cardiac sarcoidosis compared to the well-established diagnostic imaging techniques including 18F-FDG PET/CT combined with 13N-NH3 PET/CT and cardiac MRI.
3. To evaluate the potential of 68Ga-NOTA-Anti-MMR-VHH2 to assess response to standard of care treatment.
4. To explore correlations between 68Ga-NOTA-Anti-MMR-VHH2 uptake and histological (macrophage) biomarkers.
5. To explore correlations between 68Ga-NOTA-Anti-MMR-VHH2 uptake and laboratory biomarkers.

Conditions and MedDRA coding

Cardiac sarcoidosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male and female patients at least 18 years old
2. Patients with biopsy proven or probable diagnosis of cardiac sarcoidosis based on the HRS 2014 consensus criteria
3. Having available the following historical diagnostic images: o 18F-FDG PET/CT scan (Standard of care), not older than 1 month prior to screening, with patchy pattern consistent of CS o 13N-NH3 PET/CT scan (Standard of care), not older than 1 month prior to screening
4. Male patients able to father children and female patients of childbearing potential agree to use effective methods of contraception during the study

Exclusion criteria 8

1. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 3 or 4.
2. Pregnant patients / breast feeding patients.
3. Patients with inadequate organ function, suggested by the following laboratory results drawn at screening: o Significantly impaired renal function defined as estimated GFR <30 ml/min/1.73m2. o Absolute neutrophil count <1,500 cells/mm3. o Total bilirubin >1.5 x Upper Limit of Normal (ULN) (unless the patient has documented Gilbert's syndrome). o Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or Alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT) >3.0 x ULN.
4. Patients who have any other life-threatening illness, which in the opinion of the investigator would either compromise patient safety.
5. Patients at increased risk of death from a pre-existing concurrent illness with life expectancy <6 months.
6. Patients who do not speak/ understand French or Dutch.
7. Patients with contra-indications for contrast enhanced MRI and PET/CT (e.g. size, claustrophobia, known clinically relevant hypersensitivity reactions to gadolinium,…).
8. Patients with any other condition that in the opinion of the investigator may significantly interfere with study compliance (including but not limited to psychological or psychiatric, social or geographical condition potentially hampering compliance with the study requirements).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with (historical) histological proven or clinical ‘probable’ diagnosis of cardiac sarcoidosis (defined by HRS 2024 consensus recommendations) confirmed by 68Ga-NOTA-Anti- MMR-VHH2 (defined as focal/patchy uptake pattern of 68Ga-NOTA-Anti-MMR-VHH2 above background activity consistent with sarcoid involvement).

Secondary endpoints 6

1. Incidence rate of all adverse events (AEs) and serious AEs (SAEs) detected during the study procedures.
2. Comparison of semi-quantitative PET indices (SUVmax and Target-to-background ratio) between 68Ga-NOTA-Anti-MMR-VHH2 and FDG-PET/CT patients with cardiac sarcoidosis.
3. Proportion of patients with confirmed 68Ga-NOTA-Anti-MMR-VHH2 uptake (defined as 68Ga-NOTA-Anti-MMR-VHH2uptake above background activity) in sarcoidosisrelated lesions compared to LGE lesions on cardiac MRI.
4. Proportion of patients with confirmed 68Ga-NOTA-Anti-MMR-VHH2 uptake (defined as 68Ga-NOTA-Anti-MMR-VHH2uptake above background activity) in sarcoidosisrelated lesions is compared to histologically confirmed presence of M2 macrophages (if available).
5. Proportion of patients with decreased or normalized of 68Ga-NOTA-Anti-MMR-VHH2 uptake (representing presence of MMR expressing macrophages) in sarcoidosisrelated lesions after CS treatment compared to FDG PET/CT and cMRI.
6. Proportion of patients with anti-drug antibodies (ADA) against 68Ga-NOTA-Anti- MMR-VHH2.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cliniques Universitaires Saint-Luc

Sponsor organisation

Cliniques Universitaires Saint-Luc

Address

Hippokrateslaan 10, Batiment 54 Batiment 54

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

Cliniques Universitaires Saint-Luc

Contact name

Olivier Gheysens

Public contact point

Organisation

Cliniques Universitaires Saint-Luc

Contact name

Olivier Gheysens

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 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