124I-p5+14 Injection Safety in Subjects With Systemic Amyloidosis
124I-p5+14 Injection Safety in Subjects With Systemic Amyloidosis
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.
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. Thereafter, the trial will be opened to include another 40 patients
 who will be administered a single IV bolus injection of 124I-p5+14 Injection at a dose, to be
 determined in Part 1 of the study, based on the dosimetry data. Likely, 2 mCi will be used.
 Every patient participating will receive < 2 mg of peptide p5+14
Inclusion Criteria:

 -  1. Patients must have a confirmed diagnosis of systemic amyloidosis, based on
 histologic confirmation that a biopsy contains deposits of apple-green birefringent,
 Congophilic material. Additionally, the type of amyloidosis (AL, ATTR, ALect2, or
 other) should be characterized.

 -  2. Patients enrolled in Part 1 must have widespread AL amyloidosis, defined as biopsy
 proven or clinically detectable involvement, of at least two organs (excluding the
 peripheral nervous system).

 -  3. All patients will be 18 years of age or older, and there are no gender or racial
 restrictions.

 -  4. Women of child bearing potential (those who have not been surgically sterilized,
 are not postmenopausal [typically understood to mean last menstrual period >2 y ago
 without pharmaceutical intervention], and women who are fertile) must test negative
 for pregnancy in a laboratory test administered by the site physician.

 -  5. Patients who have had or are currently receiving therapy or other drug-based
 anti-amyloid regimens can be included on study.

 -  6. Patients must provide signed, written, informed consent and be willing to comply
 with eligibility requirements, scheduled visits, and follow-up studies.

 -  7. Due to annual dosimetry limitations, patients who have participated in another
 nuclear medicine amyloid imaging clinical trial protocol can be included in this study
 no earlier than 12 months after the previous radiotracer injection.

 -  8. Inclusion of patients with amyloid subsets: AL, ATTR, and ALect2 will continue
 until the trial has achieved recruitment goals for each subset: 20 AL; 10 ATTR; 5
 ALect2; and 5 "Other".

 Exclusion Criteria:

 -1. Individuals with significant cardiac dysfunction (New York Heart Association class IV -
 "Unable to carry on any physical activity without shortness of breath or angina.

 Shortness of breath at rest. If any physical activity is undertaken, discomfort increases")
 or renal insufficiency that requires dialysis.

 -  2. Those with significant co-morbidity (e.g., Eastern Cooperative Oncology Group
 (ECOG) score of 3 or greater), uncontrolled infection, or other serious illness.

 -  3. Patients with an Saturation of Peripheral Oxygen (SpO2) of ≤ 92% as noted in the
 medical record.

 -  4. Women who are of child bearing potential (those who have not been surgically
 sterilized, are not postmenopausal [typically understood to mean last menstrual period
 >2 y ago without pharmaceutical intervention], and women who are fertile), are
 pregnant, or are nursing. Women who test positive for pregnancy in a laboratory test
 administered by the site physician.

 -  5. Patients who have received any amyloidophilic radiotracer within the past 12
 months.

 -  6. Patients with exposure to heparin, or heparin-based medications, within 7 days
 prior to the imaging study.

 -  7. Patients who have a known allergy to acetaminophen, Benadryl, or iOSAT iodine
 treatment.