124I-Evuzamitide for Amyloidosis

Overseen By Jessica Cardin, MS PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Oregon Health and Science University

Must not be taking: Heparin, Heparin analogs

Disqualifiers: Severe claustrophobia, Dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

150 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you should not have received heparin or similar medications within 7 days before the study drug is given.

What data supports the effectiveness of the drug 124I-Evuzamitide for treating amyloidosis?

Research on similar treatments, like iodine-131 tositumomab, shows that radioimmunotherapy can be effective in treating certain types of lymphoma, with some patients experiencing long-lasting remissions. This suggests that using a similar approach with 124I-Evuzamitide might also be effective for amyloidosis, although direct evidence for this specific condition is not provided. ^{1 2 3 4 5}

How does the drug 124I-Evuzamitide differ from other treatments for amyloidosis?

124I-Evuzamitide is unique because it is a radiotracer that can bind to amyloid deposits from multiple types of amyloid proteins, allowing for non-invasive and quantitative detection of amyloid throughout the body using PET/CT imaging. This approach is novel compared to traditional methods, which often rely on indirect measurements and are less effective in early diagnosis and monitoring of amyloidosis. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a single center prospective study evaluating 124I-evuzumitide in patients with systemic amyloidosis. The purpose of this study is to 1)identify and characterize the distribution and uptake of 124I-evuzumitide in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and 2) Correlate the uptake with the structure and function of different organs, including the heart. To achieve these goals, eligible patients will undergo primarily hybrid positron emission tomography and magnetic resonance imaging (PET/MRI). In a subgroup of patients who are unable to undergo PET/MR, computed tomography will be used instead of MRI (i.e. PET/CT). In a subgroup of patients, repeat imaging with the same modality will be done at a interval of 6-12 months. Clinically available data (demographics, phenotype, imaging, laboratory) will also be collected to characterize the disease in each patient.

Eligibility Criteria

This trial is for people with systemic amyloidosis, specifically those who have a mutation in the transthyretin gene and known organ involvement. It's also open to patients with multiple myeloma or monoclonal gammopathy of undetermined significance. People can't join if they're allergic to potassium iodide or gadolinium, have severe kidney issues, recently used heparin products, or can't complete imaging procedures due to claustrophobia or other conditions.

Inclusion Criteria

I have been diagnosed with multiple myeloma.

Patient willing to consent for the study and undergo the study procedures

I carry a mutation in the transthyretin gene.

Exclusion Criteria

You are allergic to potassium iodide or gadolinium.

I am on dialysis or my kidney function is very low.

You have extreme fear of enclosed spaces or any medical condition that would make it difficult for you to complete the imaging tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo hybrid 124I-Evuzamitide PET/MRI imaging (or PET/CT) to evaluate distribution and uptake

1 day

1 visit (in-person)

Follow-up Imaging

In a subgroup of patients, repeat imaging with the same modality will be done at an interval of 6-12 months

6-12 months

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• 124I-Evuzamitide

Trial Overview The study is testing how well Iodine-124 Evuzumitide (AT-01) shows up in different organs of patients with amyloidosis using advanced imaging techniques like PET/MRI scans. Some may get PET/CT scans instead. The goal is to see where the drug goes in the body and how it relates to heart structure and function over time.

Participant Groups

Group I: Patients with ATTR-CM Experimental Treatment 1 Intervention

Patients with ATTR-CM will undergo hybrid 124I-Evuzamitide PET/MRI imaging (or PET/CT) at baseline and in a subgroup, repeat imaging will be performed at an interval of 6-12 months.

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Attralus, Inc.

Industry Sponsor

Trials

8

Recruited

670+

Findings from Research

In a Phase I clinical study involving 34 patients with B-cell non-Hodgkin's lymphoma (NHL), 79% of patients achieved a response to iodine-131 anti-B1 antibody radioimmunotherapy, with 50% achieving a complete response (CR) and some CRs lasting over 1000 days.

The study established a maximum tolerated dose of 75 cGy for patients without prior bone marrow transplantation, with longer durations of CR associated with higher total-body radiation doses, suggesting that this therapy could lead to durable responses and improved survival rates in NHL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iodine-131 anti-B1 antibody for B-cell lymphoma: an update on the Michigan Phase I experience. Wahl, RL., Zasadny, KR., MacFarlane, D., et al.[2019]

In a phase I trial involving 23 patients with chemotherapy-resistant B-cell non-Hodgkin's lymphoma, the combination of iodine-131 tositumomab and high-dose BEAM chemotherapy followed by autologous stem-cell transplantation resulted in a complete response rate of 57% and an overall response rate of 65%.

The addition of iodine-131 tositumomab at doses up to 0.75 Gy did not increase short-term or long-term toxicities compared to historical controls treated with BEAM alone, suggesting it is a safe and potentially effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma. Vose, JM., Bierman, PJ., Enke, C., et al.[2019]

Iodine-131 tositumomab, combined with unlabelled tositumomab, effectively targets CD20 on B-cells and has shown durable remissions in patients with relapsed or refractory follicular lymphoma, leading to its FDA approval in 2003.

This treatment has a favorable safety profile compared to traditional chemotherapy, with primarily hematological toxicity and a single nadir at 4-6 weeks post-therapy, although there are concerns about long-term risks like therapy-related myelodysplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tositumomab and iodine [131I] tositumomab in the management of follicular lymphoma. An oncologist's view. Davies, AJ.[2019]

In a phase IA trial involving 18 patients with recurrent non-Hodgkin's lymphoma, the iodine 131 labeled OKB7 treatment showed antitumor activity in 13 patients, indicating its potential effectiveness in this heavily pretreated group.

The treatment was generally safe, with manageable toxicity; the maximum tolerated dose was determined to be 200 mCi, and only limited nonhematologic toxicity was observed, suggesting that further investigation in phase II trials is justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma. Czuczman, MS., Straus, DJ., Divgi, CR., et al.[2017]

In a study of 59 patients with chemotherapy-relapsed/refractory B-cell non-Hodgkin lymphoma, treatment with iodine (131)I tositumomab resulted in a 71% overall response rate, with 34% achieving complete responses, particularly benefiting those with low-grade or transformed NHL.

The treatment was generally well-tolerated, with manageable reversible hematologic toxicity, although some long-term side effects were noted, including elevated thyroid-stimulating hormone levels and cases of myelodysplasia and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Kaminski, MS., Estes, J., Zasadny, KR., et al.[2021]

A case study of multiple myeloma revealed extensive amyloid deposits in joints and small blood vessels, indicating a significant relationship between amyloidosis and this type of cancer.

A specific monoclonal antibody (MAb Am-1) was developed that can identify certain amyloid proteins, showing potential for diagnosing and understanding amyloid-related diseases, as it reacted with amyloid deposits resistant to potassium permanganate treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of monoclonal antibody against amyloid fibril protein and its immunohistochemical application. Kurashima, C., Hirokawa, K.[2015]

The first-in-human study of the iodine-124 labeled peptide 124I-p5+14 demonstrated that it is well tolerated and rapidly accumulates in organs commonly affected by amyloidosis, such as the heart, kidneys, and liver, indicating its potential for effective imaging of amyloid deposits.

Dosimetry estimates for 124I-p5+14 were found to be acceptable for whole-body PET/CT imaging, with a low effective radiation dose of 0.23 mSv/MBq, suggesting that this imaging technique could be a safe and non-invasive method for diagnosing systemic AL amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First in Human Evaluation and Dosimetry Calculations for Peptide 124I-p5+14-a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET/CT Imaging. Wall, JS., Martin, EB., Endsley, A., et al.[2022]

In a Phase I study involving 18 patients with AL amyloidosis, the antibody 11-1F4 showed significant uptake in various organs, including the liver and spleen, which could help in assessing disease extent.

The imaging results from PET/CT scans correlated well with traditional tissue biopsy findings, suggesting that the labeled antibody could be a useful tool for identifying patients suitable for passive immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Wall, JS., Kennel, SJ., Stuckey, AC., et al.[2021]

The peptide p5+14 can non-invasively detect all types of systemic amyloidosis by binding to amyloid deposits, which is crucial for early diagnosis and better patient outcomes.

In a Phase 1/2 clinical trial involving 8 patients with different types of amyloidosis, PET/CT imaging showed that the iodine-124-labeled p5+14 effectively localized amyloid deposits in affected organs, confirming its potential as a diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide 124I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging. Martin, EB., Stuckey, A., Powell, D., et al.[2023]

The novel radiotracer 124I-evuzamitide effectively quantifies cardiac amyloid deposits, showing significant differences in uptake between amyloid cardiomyopathy (CMP) patients and control subjects, which could enhance early diagnosis and treatment monitoring.

In patients with wild-type transthyretin (ATTRwt) CMP, 124I-evuzamitide demonstrated superior performance in detecting cardiac amyloid compared to the existing radiotracer 18F-florbetapir, indicating its potential as a more effective diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study. Clerc, OF., Cuddy, SAM., Robertson, M., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Iodine-131 anti-B1 antibody for B-cell lymphoma: an update on the Michigan Phase I experience. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

Tositumomab and iodine [131I] tositumomab in the management of follicular lymphoma. An oncologist's view. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Production of monoclonal antibody against amyloid fibril protein and its immunohistochemical application. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

First in Human Evaluation and Dosimetry Calculations for Peptide 124I-p5+14-a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET/CT Imaging. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide 124I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study. [2023]