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

NCT ID: NCT06974877

Last Updated: 2025-09-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-10

Study Completion Date

2032-01-31

Brief Summary

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Background:

Anakinra is a drug used to treat people with certain diseases that affect their immune systems. Sometimes anakinra can cause proteins under the skin to clump together. These clumps are called amyloidosis; they can spread to other organs. The only way to diagnose amyloidosis is to remove a piece of tissue (biopsy). Researchers want to find a way to locate amyloidosis in internal organs using positron emission tomography (PET)/computed tomography (CT).

Objective:

To test a new tracer used during PET/CT scans in people with amyloidosis. A tracer is a radioactive dye injected into the body.

Eligibility:

Adults aged 18 years or older with amyloidosis from anakinra injections. They must be enrolled in NIH protocol 17-I-0016.

Design:

Participants will come to the clinic once every 6 months for 2 years. Each visit will be 1 day.

They will have a PET/CT scan with the new tracer at each visit: The tracer will be given through a tube attached to a needle inserted into a vein.

The PET/CT scanner is a machine shaped like a doughnut. Participants will lie still on a padded table. The table will move in and out of the machine. The scan takes about 1 hour.

Radiation from the tracer will remain in the body for 24 hours after each scan. Participants will need to follow rules to avoid exposing pets and other people.

Participants will collect a 24-hour urine sample before each visit. They will also have blood tests and a physical exam at each visit.

Participants will receive a follow-up phone call about 1 week after each visit.

Detailed Description

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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:

1. 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.
2. 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.
3. 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.

Conditions

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Cryopyrin-Associated Periodic Syndromes Amyloidosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Interventional

Participants aged 18 years and older with anakinra-type amyloidosis (n=10) will be recruited from NIH protocol 17-I-0016. Upon confirmation of eligibility, they will undergo a PET/CT scan with the investigational radiotracer 124I-AT-01, which selectively binds to amyloid fibers. Blood and urine will also be collected for clinical and research analyses, including measurement of IL-1RA and other biomarkers. These scans and sample collections will be repeated about once every 6 months for 2 years.

Group Type EXPERIMENTAL

124I AT-01

Intervention Type DRUG

124I-AT-01 is an amyloid-reactive synthetic 45-L amino acid polypeptide radiolabeled with iodine-124, with a theoretical molecular weight of 4763.6 Da (based on amino acid sequence). The polypeptide, AT-01, is not pharmacologically active. 124I-AT-01 binds many forms of human and murine amyloid and is intended to be a PET imaging agent for the detection of amyloid deposits.

Interventions

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124I AT-01

124I-AT-01 is an amyloid-reactive synthetic 45-L amino acid polypeptide radiolabeled with iodine-124, with a theoretical molecular weight of 4763.6 Da (based on amino acid sequence). The polypeptide, AT-01, is not pharmacologically active. 124I-AT-01 binds many forms of human and murine amyloid and is intended to be a PET imaging agent for the detection of amyloid deposits.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

1. Aged 18 years and older.
2. Currently enrolled on NIH protocol 17-I-0016 with a documented diagnosis of MWS or NOMID.
3. 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.
4. Developed skin thickening at the site of anakinra injection.
5. 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:

1. Barrier methods:

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

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

Exclusion Criteria

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

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sara Alehashemi, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Sara Alehashemi, M.D.

Role: CONTACT

(301) 761-7570

Facility Contacts

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NIH Clinical Center Office of Patient Recruitment (OPR)

Role: primary

800-411-1222 ext. TTY dial 711

Sara Alehashemi, M.D.

Role: backup

(301) 761-7570

References

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Alehashemi S, Dasari S, Metpally A, Uss K, Castelo-Soccio LA, Heller T, Kellman P, Chen MY, Ahlman M, Kim J, Wargo S, Kuhns DB, Fink D, de Jesus A, Martin PS, Chang R, Bolanos J, Lee CR, Nasr SH, Goldbach-Mansky R, McPhail E. Anakinra-Associated Systemic Amyloidosis. Arthritis Rheumatol. 2024 Jan;76(1):100-106. doi: 10.1002/art.42664. Epub 2023 Nov 29.

Reference Type BACKGROUND
PMID: 37488949 (View on PubMed)

Nasr SH, Alehashemi S, Dasari S, Waldman M, Afzali B, Chiu A, Bolanos J, Goldbach-Mansky R, McPhail ED. Anakinra-associated renal amyloidosis. Kidney Int. 2024 Feb;105(2):395-396. doi: 10.1016/j.kint.2023.08.020. No abstract available.

Reference Type BACKGROUND
PMID: 38245224 (View on PubMed)

Alehashemi S, Dasari S, de Jesus AA, Cowen EW, Lee CR, Goldbach-Mansky R, McPhail ED. Anakinra-Associated Amyloidosis. JAMA Dermatol. 2022 Dec 1;158(12):1454-1457. doi: 10.1001/jamadermatol.2022.2124.

Reference Type BACKGROUND
PMID: 36223107 (View on PubMed)

Related Links

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Other Identifiers

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001867-I

Identifier Type: -

Identifier Source: secondary_id

10001867

Identifier Type: -

Identifier Source: org_study_id

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