124I-p5+14 Injection Safety in Subjects With Systemic Amyloidosis
- Registration Number
- NCT03678259
- Lead Sponsor
- University of Tennessee Graduate School of Medicine
- Brief Summary
This is a single-center, exploratory, Phase 1 Positron Emission Tomography/x-ray Computed Tomography (PET/CT) imaging study to detect amyloidosis that will enroll patients with a confirmed diagnosis of systemic amyloidosis. The purpose of this exploratory trial is to assess the safety and efficacy of 124I-p5+14 Injection at a single-injection dose adequate for imaging amyloid deposits by using PET/CT imaging in subjects with confirmed systemic Immunoglobulin Light Chain-associated Amyloidosis (AL), Transthyretin-associated Amyloidosis (ATTR), Leukocyte Chemotactic Factor 2-associated Amyloidosis (ALect2) as well as other types.
- Detailed Description
The rationale for this study is the discovery of a synthetic polypeptide, designated p5+14, a synthetic 45 amino acid peptide that binds many forms of amyloid, including human AL-, ATTR- and ALect2-associated amyloid, as well as human and murine serum amyloid protein A-associated (AA) amyloid. In preclinical studies, using SPECT and PET imaging, as well as microautoradiography, it has been shown that radioiodinated p5+14 binds rapidly and specifically to all amyloid deposits in abdominothoracic organs and tissues.
This is a single site, exploratory, open-label Phase I PET/CT imaging and dosimetry study. The investigational drug product (designated 124I-p5+14 Injection) is an amyloid-reactive synthetic peptide, p5+14 (also known as APi1832), radiolabeled with iodine-124 (I-124 or 124I). All patients enrolled in this exploratory trial will be outpatients with a confirmed diagnosis of systemic amyloidosis.
The first three patients enrolled in the trial (Part 1) will take part in a dose-escalation dosimetry study and will receive a single intravenous (IV) dose of 11.1 Megabecquerel (MBq) (0.3 millicuries (mCi); n = 1), 37 MBq (1 mCi; n = 1) or 74 MBq (2 mCi; n = 1) of 124I-p5+14 Injection for the purpose of determining estimates of organ-associated and whole body radioactive dosimetry.
The trial then will be opened to include another 54 patients who will receive a single IV bolus injection of 2 mCi 124I-p5+14 Injection. Every patient participating will receive \< 2 mg of peptide p5+14. The study comprises five parts.
In Part 2, the trial will enroll SA patients with confirmed AL, ATTR, ALECT2, or other forms of amyloidosis.
In Part 3, the trial will study asymptomatic subjects with genetically confirmed mutation of the transthyretin gene.
Part 4 will include five healthy control subjects. Part 5 will recruit previously enrolled subjects from Parts 2 or 3 who received a 2 mC dose of 124I-p5+14 Injection and had images confirming the presence of abnormal amyloid deposits for a second exposure to 124I p5+14 Injection and second PET/CT scan.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 124I-p5+14 Injection 124I-p5+14 Injection A single-injection dose of 124I-p5+14 adequate for imaging amyloid deposits by using PET/CT imaging in subjects with confirmed systemic amyloidosis of several sub-types.
- Primary Outcome Measures
Name Time Method Organ-specific radioactivity dosimetry (Part 1). Through 48 hours Localization of 124I-p5+14 will be taken from PET/CT images performed at intervals during the 48 hours after injection. Organ-specific dosimetry and whole body dose measurements will be made using Olinda software (Olinda/Exp; Organ Level Internal Dose Assessment/Exponential Modeling)
- Secondary Outcome Measures
Name Time Method Absolute values and changes from baseline in clinical laboratory values. Baseline and 24 hours Laboratory assessments will include hematology and clinical chemistry.
Clinically defined amyloidosis organ involvement. Baseline For each subject, the clinician/investigator will designate each organ as involved or not involved with amyloidosis, based on available medical history including prior imaging, prior biopsy results, and clinical laboratory values.
Measure of background radioactivity uptake. 6 hours and 24 hours For each subject, a background radioactivity uptake measure will be derived from the PET images at an uninvolved anatomic site (the lumen of a large blood vessel).
Measure of radioactivity uptake by each organ 6 hours and 24 hours Uptake of 124I-p5+14 will be derived from PET/CT scans performed at 6 hours and 24 hours after injection. Any organ with \>=2-fold higher accumulation of radiotracer, relative to the background uptake, will be considered positive.
Concentration of radiotracer in specific anatomic sites, for each subject and anatomic site 6 hours and 24 hours Concentration of 124I-p5+14 will be derived from PET/CT scans performed at 6 hours and 24 hours after injection.
Correlation between concentration of the radiotracer (Bq/cc) in the kidney with organ-associated clinical biomarkers. 6 hours and 24 hours Statistical correlation of kidney radiotracer uptake with proteinuria, albuminuria, creatinine, and blood urea nitrogen (BUN).
Peptide uptake in the heart. 6 hours and 24 hours Peptide uptake will be recorded as the Standard Uptake Value (SUV) or as Bq/cc of organ volume; obtained from the Region of Interest (ROI) analysis
Organ and tissue-specific sensitivity of the 124I-p5+14 Injection radiotracer 6 hours and 24 hours Sensitivity for each organ will be derived from the list of clinically involved organs (Secondary Measure 1) and the list of organ radioactivity uptake (Secondary Measure 4), using the formula, true positive rate = \[True positive/(True positive + False negative)\].
Peptide uptake in the kidney 6 hours and 24 hours Peptide uptake will be recorded as the Standard Uptake Value (SUV) or as Bq/cc of organ volume; obtained from the Region of Interest (ROI) analysis.
Peptide uptake in organ(s) other than kidney or heart if clinically relevant 6 hours and 24 hours Peptide uptake will be recorded as the Standard Uptake Value (SUV) or as Bq/cc of organ volume; obtained from the Region of Interest (ROI) analysis
Correlation between concentration of the radiotracer (Bq/cc) in the heart with organ-associated clinical biomarkers. 6 hours and 24 hours Statistical correlation of heart radiotracer uptake with N-terminal-pro-brain natriuretic peptide (NT-BNP) or Brain Natriuretic Peptide (BNP) serum levels, intraventricular septal thickness, and ejection fraction (measures as available from medical history)
Correlation between uptake of peptide and clinical status of kidney, heart and other organs Baseline and 24 hours Correlation between uptake of peptide (from ROI measurements) and the clinical status of kidney, heart, and other organs if indicated (clinical status defined as in Secondary Endpoint 1).
Trial Locations
- Locations (1)
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States