Molecular Imaging of the Underlying Mechanism of Cardiotoxicity in Patients With Light Chain Amyloidosis Using PET/CT

NCT04105634 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: 833485
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The research study is being conducted to test how two different types of Positron Emission Tomography (PET/CT) scans could be used to image a type of heart disorder called amyloidosis (AL). There will be two groups in the study. One group will have PET/CT scans using an imaging drug called 18F-NOS and the other group will have PET/CT scans using a drug called Florbetaben. subject will be assigned to one of the groups when she/he agrees to be in the study.

Conditions

Cardiac Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy using PET/CT

  Measure uptake of \[18F\]NOS and Florbetaben in patients with AL before and \~4 months (2 +/- weeks) after starting standard therapy and describe the distributions of uptake values at each time point. Compute post-/pre-treatment fold change in \[18F\]NOS and Florbetaben uptake and describe its distribution.

  4 months

Secondary Outcomes (3)

• Describe fold changes in [18F]NOS uptake in patients who have a complete response or very good partial response vs patients who have a partial or no response to therapy at ~4 months.

  4 months

• Describe fold changes in [18F]NOS uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression

  4 months

• Describe fold changes in Florbetaben uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression

  4 months

Study Arms (2)

Inflammation group

EXPERIMENTAL

Patient diagnosed with Cardiac Amyloidosis

Drug: FNOS

Amyloid group

EXPERIMENTAL

Patient diagnosed with Cardiac Amyloidosis

Drug: Florbetaben

Interventions

FNOS DRUG

The imaging drug used for this group is called 18F-NOS, it is an experimental imaging drug that has not yet been approved by the Food and Drug Administration (FDA) for use except in a research study. Subject will not receive the results or feedback from the study participation, the images may be reviewed with subject or her/his doctor upon request but will not be used to make decisions about subject medical care.

Also known as: [18F]-6-(2-fluoro-propyl)-4-methylpyridin-2-amine

Inflammation group

Florbetaben DRUG

The imaging drug used for this group is called Florbetaben, it is an FDA approved radioactive PET tracer used to image amyloid plaques in the body. Although not yet FDA approved for this purpose, it has already been used clinically to image amyloid in other parts of the body. Subject will not receive the results or feedback from the study participation, the images may be reviewed with subject or her/his doctor upon request but will not be used to make decisions about subject medical care.

Also known as: Neuraceq

Amyloid group

Eligibility Criteria

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

You may qualify if:

• Participants will be at least 18 years of age
• Have an established diagnosis of AL amyloidosis based on standard criteria and planning to start systemic therapy.
• Have cardiac involvement as defined by all of the following:
• Past documented or presently noted clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure
• Either an endomyocardial biopsy demonstrating AL amyloidosis or an echocardiogram demonstrating a mean left ventricular wall thickness at diastole \>12mm in the absence of other causes (e.g. severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening
• NT-proBNP ≥ 650 pg/mL
• Participants should fall into 1 of the following 2 categories:
• Treatment-naïve or have completed no more than 1 cycle of initial therapy, OR
• Relapsed after 1 or more prior therapies, and at least 6 months from last treatment
• Have serum free light chain (FLC) differential (defined as amyloid-forming FLC minus non-amyloid-forming FLC) ≥ 50 mg/L.
• Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

You may not qualify if:

• Females who are pregnant or breast feeding at the time of the PET/CT scan will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential before the injection of radiotracer.
• Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
• Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
• Less than 6 months life expectancy as deemed by a treating physician

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Amyloid Neuropathies, Familial

Interventions

4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Study Officials

• Paco Bravo

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 26, 2019
• Study Start: October 1, 2019
• Primary Completion: October 14, 2024
• Study Completion: October 14, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Locations

US (1)