Repeat PET/CT Imaging of Patients With Amyloid 124I-AT-01 to Measure Changes in Organ-specific Amyloid Load

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Primary Purpose

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Injection of peptide p5+14 radiolabeled with iodine-124 (124I-AT-01)

About this trial

This is an interventional basic science trial for Systemic Amyloidosis focused on measuring systemic amyoidosis, p5+14, AT-01, PET/CT, evuzamitide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements. Must have a diagnosis of systemic amyloidosis based on the patient's medical record. Must have undergone PET/CT imaging with 124I-AT-01 as part of the AMY1001 study (IND #132282) with visually positive uptake of radiotracer in at least one abdominothoracic organ. Must have been imaged with 124I-AT-01 as part of the AMY1001 study (IND #132282) more than 12 months prior to repeat imaging. Females: must be non-pregnant and non-lactating and either: surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the laboratory involved). Exclusion Criteria: Disabling dementia or other mental or behavioral disease. Patients on dialysis. Inability or unwillingness to comply with the study requirements. Patients taking heparin, or heparin derivatives (e.g. low molecular weight heparins) for anticoagulation. Other reason that would make the subject inappropriate for entry into this study. Inability to lie still for 60 minutes on the PET/CT scanner. History of iodine (potassium iodide) allergy. Positive ADA finding defined as significantly higher than normal human serum mean values AND with a mean value at least five times greater than the mean value of the normal human serum control.

Sites / Locations

University of Tennessee Graduate School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients will receive a single IV injection of 124I-AT-01 radiotracer and PET/CT imaging

Arm Description

124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is an iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging. The peptide binds many forms of amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans. 124I-AT-01 has been evaluated previously in an open-label Phase 1/2 clinical trial, AMY1001, performed at the University of Tennessee Medical Center (IND# 132282; NCT T03678259). In this repeat imaging study, patients previously enrolled in the AMY1001 study, in whom positive PET/CT imaging findings were observed will undergo repeat imaging to assess changes in radiotracer uptake in the liver, spleen, heart and kidneys.

Outcomes

Primary Outcome Measures

To measure visual and quantitative changes in organ-specific uptake of 124I-AT-01

The goal of this research study is to determine whether changes in organ-specific uptake of 124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate with changes in a subject's disease status and thereby enable monitoring of disease response over time in terms of organ-specific amyloid load. The specific aim of this study is to measure visual and quantitative changes in organ-specific uptake of 124I-AT-01 from baseline, in patients with systemic amyloidosis, using PET/CT imaging.

Secondary Outcome Measures

Full Information

NCT ID

NCT05968846

First Posted

June 30, 2023

Last Updated

July 28, 2023

Sponsor

University of Tennessee Graduate School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT05968846

Brief Title

Repeat PET/CT Imaging of Patients With Amyloid 124I-AT-01 to Measure Changes in Organ-specific Amyloid Load

Official Title

Repeat PET/CT Imaging of Patients With Systemic Amyloidosis Using Amyloid Reactive Peptide 124I-AT-01 (124I-p5+14, Iodine-124I-evuzamitide) to Measure Changes in Organ-specific Amyloid Load

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 7, 2022 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Tennessee Graduate School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

Brief Summary

The goal of this research study is to determine whether changes in organ-specific uptake of 124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate with changes in a subject's disease status and thereby enable monitoring of disease response over time in terms of organ-specific amyloid load.

Detailed Description

This is a single center, open label, prospective study using 124I-AT-01 PET/CT imaging to evaluate changes in amyloid load in patients with systemic amyloidosis who had undergone 124I-AT-01 imaging. Consented eligible patients will provide 3 tablespoons of blood for the following laboratory tests: CMP, CBC, CRP, Troponin, NT-proBNP, LDH, FLC and anti-drug antibody (ADA) analyses. A urine sample will also be collected to assess renal function. If required, a pregnancy test will be administered. Patients will then undergo a transthoracic echocardiographic examination and vital sign assessment before receiving an intravenous injection of no more than 2 mCi 124I-AT-01 followed, 5 h thereafter, by repeat vital sign measurements and PET/CT imaging from crown to thighs with a dynamic PET acquisition over the heart. Previously acquired 124I- AT-01 PET/CT images will be used as baseline values to determine quantitative changes in uptake of the radiotracer in the heart, liver, spleen, and kidney (and other organs deemed positive following visual inspection of the baseline and repeat imaging) as a measure of changes in amyloid load. Optionally, if the patients can return to the study site within ~30 days post injection of 124I-AT-01, a second (post-injection) blood draw and ADA evaluation will be performed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Systemic Amyloidosis

Keywords

systemic amyoidosis, p5+14, AT-01, PET/CT, evuzamitide

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Patients will receive a single IV injection of 124I-AT-01 radiotracer and PET/CT imaging

Arm Type

Experimental

Arm Description

124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is an iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging. The peptide binds many forms of amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans. 124I-AT-01 has been evaluated previously in an open-label Phase 1/2 clinical trial, AMY1001, performed at the University of Tennessee Medical Center (IND# 132282; NCT T03678259). In this repeat imaging study, patients previously enrolled in the AMY1001 study, in whom positive PET/CT imaging findings were observed will undergo repeat imaging to assess changes in radiotracer uptake in the liver, spleen, heart and kidneys.

Intervention Type

Drug

Intervention Name(s)

Injection of peptide p5+14 radiolabeled with iodine-124 (124I-AT-01)

Other Intervention Name(s)

124I-p5+14, iodine-124-evuzamitide

Intervention Description

124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is a a novel iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging that has been shown to bind systemic amyloid deposits of diverse types in all organs, including the heart. The peptide binds amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans.

Primary Outcome Measure Information:

Title

To measure visual and quantitative changes in organ-specific uptake of 124I-AT-01

Description

The goal of this research study is to determine whether changes in organ-specific uptake of 124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate with changes in a subject's disease status and thereby enable monitoring of disease response over time in terms of organ-specific amyloid load. The specific aim of this study is to measure visual and quantitative changes in organ-specific uptake of 124I-AT-01 from baseline, in patients with systemic amyloidosis, using PET/CT imaging.

Time Frame

From enrollment to the end of the study is 8 days

Other Pre-specified Outcome Measures:

Title

Measures of Interest

Description

For AL, ATTR and all patients, we will correlate visual and quantitative changes in 124I- AT-01 uptake, from baseline, in the heart, liver and kidney with echocardiographic parameters (including left ventricular wall thickness (cm), intraventricular wall thickness (cm), and global logitudinal strain (%)) and serum biomarker levels (including NTproBNP, eGFR, creatinine, AST and ALT) assessed prior to imaging and from data recorded in the patients' medical record.

Time Frame

From enrollment to the end of the study is 8 days

Title

Measure of Interest

Description

For AL, ATTR and all patients, we will correlate visual and quantitative changes in organ-specific 124I-AT-01 uptake (percent change in radiotracer uptake from baseline) with change in disease status (progression, response, or stable state) when this can be established from data (serum biomarkers and cardiac imaging parameters) in the patients' medical record or collected during the AMY1001 trial.

Time Frame

From enrollment to the end of the study is 8 days

Title

Measure of Interest

Description

For all patients, correlate organ-specific percent change in radiotracer uptake with type of therapeutic intervention and assess qualitatively whether the patient feels that their disease is improving or worsening.

Time Frame

From enrollment to the end of the study is 8 days

Title

Measure of interest

Description

For AL patients, correlate visual and quantitative changes in organ-specific 124I-AT-01 uptake (percent change in radiotracer uptake from baseline) with change in serum free light chains over the period between imaging studies, when available in the medical record.

Time Frame

From enrollment to the end of is the study is 8 days

Title

Measure of Interest

Description

Compare changes, when possible, in radiotracer distribution from baseline based on analysis dynamic PET data.

Time Frame

From enrollment to the end of the study is 8 days

Title

Measure of Interest

Description

Compare changes, when possible, in ejection fraction from baseline based on analysis dynamic PET data.

Time Frame

From enrollment to the end of the study is 8 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements. Must have a diagnosis of systemic amyloidosis based on the patient's medical record. Must have undergone PET/CT imaging with 124I-AT-01 as part of the AMY1001 study (IND #132282) with visually positive uptake of radiotracer in at least one abdominothoracic organ. Must have been imaged with 124I-AT-01 as part of the AMY1001 study (IND #132282) more than 12 months prior to repeat imaging. Females: must be non-pregnant and non-lactating and either: surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the laboratory involved). Exclusion Criteria: Disabling dementia or other mental or behavioral disease. Patients on dialysis. Inability or unwillingness to comply with the study requirements. Patients taking heparin, or heparin derivatives (e.g. low molecular weight heparins) for anticoagulation. Other reason that would make the subject inappropriate for entry into this study. Inability to lie still for 60 minutes on the PET/CT scanner. History of iodine (potassium iodide) allergy. Positive ADA finding defined as significantly higher than normal human serum mean values AND with a mean value at least five times greater than the mean value of the normal human serum control.

Facility Information:

Facility Name

University of Tennessee Graduate School of Medicine

City

Knoxville

State/Province

Tennessee

ZIP/Postal Code

37920

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Systemic Amyloidosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial