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

NCT06974877 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001867001867-I
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyloidosis; Cryopyrin-Associated Periodic Syndromes

Keywords

Muckle-Wells Syndrome; Neonatal Onset Multisystem Inflammatory Disease; Interleukin 1 Receptor Antagonist Protein; Anakinra; AMYLOIDOSIS; AIL1RAP

Outcome Measures

Primary Outcomes (2)

• 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.

  The gold standard for detecting amyloid deposits is tissue biopsy. With this compound, we expect to detect evidence of tissue deposits in the tissue at a much earlier stage and in a non invasive manner. By lowering the exposure to anakinra in participants with anakinra-associated systemic amyloidosis, the burden of amyloidosis is expected to reduce over time.

  2 years

• Frequency of CAPS disease flares after exposure to 124I AT 01.

  This compound has not been used in patients with CAPS. We will monitor the participants to detect possible inflammatory disease flare following the exposure.

  Through end of study.

Study Arms (1)

Interventional

EXPERIMENTAL

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.

Drug: 124I AT-01

Interventions

124I AT-01 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.

Interventional

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 37488949 BACKGROUND

• 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.

  PMID: 38245224 BACKGROUND

• 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.

  PMID: 36223107 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cryopyrin-Associated Periodic Syndromes; Amyloidosis

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Inducible Urticaria; Chronic Urticaria; Urticaria; Skin Diseases, Vascular; Cold Urticaria; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Sara Alehashemi, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara Alehashemi, M.D.

CONTACT

(000) 000-0000; sara.alehashemi@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: May 16, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): January 31, 2032
• Last Updated: April 8, 2026

Record last verified: 2026-02-13

Data Sharing

• IPD Sharing: Will share
• Time Frame: At the time of publication.
• Access Criteria: Data will be shared in closed access repositories. PI will assess qualifications of other requests for data access.

Locations

US (1)