Repeat PET/CT Imaging in People With CAPS and Anakinra-Induced Amyloidosis Using an Amyloid-Reactive Peptide to Measure Changes in Organ-Specific Amyloid Load

Study Description:

This is a phase 1 study to evaluate the feasibility of an investigational positron emission tomography (PET)/computed tomography (CT) radiotracer, 124I-AT-01, to screen for anakinra-induced amyloidosis in people with the cryopyrin-associated autoinflammatory syndromes (CAPS) (Muckle-Wells syndrome [MWS] or neonatal onset multisystem inflammatory disease [NOMID]), and to follow resolution of amyloidosis. This radiotracer binds to amyloid, so a PET/CT scan can show the presence and relative magnitude of amyloid.

Participants aged 18 years and older who developed local skin or systemic amyloidosis as a result of anakinra treatment will be recruited. They will have a PET/CT scan with radiotracer 124I-AT-01 about once every 6 months for 2 years. Blood and urine will be collected for clinical safety analyses, but no specimen will be collected for research or storage purposes.

The 124I-AT-01 PET/CT imaging is expected to be able to detect anakinra-induced amyloid in the skin and other organs (such as kidney, liver, and spleen). The percent change in quantitative uptake of 124I-AT-01 from baseline to each subsequent scan is expected to correlate with changes in clinical features related to load of amyloid in the body.

Primary Objectives:

• To screen participants with fixed skin thickening at the site of anakinra injection and/or biopsy-proven anakinra-induced amyloidosis of the skin for the presence of systemic amyloidosis, using 124I-AT-01 PET/CT imaging.
• To measure changes in organ-specific uptake of 124I-AT-01 from baseline in participants with anakinra-induced amyloidosis (local or systemic) using PET/CT imaging.
• To assess the safety profile of 124I-AT-01 in participants with CAPS.

Primary Endpoints:

Change in organ-specific 124I-AT-01 uptake from baseline PET/CT imaging to the follow-up PET/CT imaging every 6 months for 2 years. Frequency of CAPS disease flares after exposure to 124I-AT-01.

• INCLUSION CRITERIA:

An individual must meet all the following criteria to be eligible for this study:

• Aged 18 years and older.
• Currently enrolled on NIH protocol 17-I-0016 with a documented diagnosis of MWS or NOMID.
• Agree to allow data collected in this study to be shared with and stored on NIH protocol 17-I-0016 for that study s research analyses.
• Developed skin thickening at the site of anakinra injection.
• Participants who can become pregnant or who can impregnate their partner must agree to use 2 highly effective methods of contraception, at least 1 of which must be a barrier method, when engaging in sexual activities that can result in pregnancy, beginning 28 days prior to baseline until 90 days after the last PET/CT scan. Acceptable methods of contraception include the following:

• Barrier methods:

• External or internal condom with spermicide.
• Diaphragm or cervical cap with a spermicide.
• Non-barrier methods:

• Hormonal contraception.
• Intrauterine device.
• Hysterectomy, oophorectomy, or tubal ligation in women
• Vasectomy in men
• Other.

Exclusion criteria

• Known hypersensitivity to 124I-AT-01, AT-01, or any of their excipients.
• Known hypersensitivity to KI.
• Pregnant or breastfeeding.
• Currently receiving dialysis.
• Currently taking heparin or heparin derivatives (eg, low molecular weight heparins) or other blood thinners for anticoagulation.
• Any condition that, in the opinion of the study team, contraindicates participation in this study.