| Eligibility |
Subjects included in this trial are volunteers with a confirmed diagnosis of systemic
amyloidosis, a genetically well-defined mutation of the TTR gene but without clinical
evidence of active disease, and at an age typical of development of symptomology = 50, or
healthy control subjects (=30 years).
Prior to participation in Parts 1 or 2 of the trial (n = 73), the following inclusion
criteria must be met
Subjects included in this trial are volunteers with a confirmed diagnosis of systemic
amyloidosis, a genetically well-defined mutation of the TTR gene but without clinical
evidence of active disease, and at an age typical of development of symptomology = 50, or
healthy control subjects (=30 years).
Prior to participation in Parts 1 or 2 of the trial (n = 73), the following inclusion
criteria must be met:
1. Patients must have a confirmed diagnosis of systemic amyloidosis, based on either a
histologic confirmation that a biopsy contains deposits of apple-green birefringent,
Congophilic material or genetic screening and presence of amyloid-related pathology,
or amyloid-specific imaging study. Additionally, the type of amyloidosis (AL, ATTR,
ALect2, or other) should be characterized.
2. Patients enrolled in Part 1 (n = 3) 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 in Parts 1 and 2 will be 18 years of age or older. 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 (Parts 1 and 2).
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. In Part 2, inclusion of patients with amyloid subsets AL, ATTR, and ALect2 will
continue until the trial has achieved recruitment goals for each subset: 30 AL; 20
ATTR; 5 ALect2; and 10 15 "Other".
Prior to participation in Part 3 (n = 10 subjects) of the trial, the following inclusion
criteria must be met:
1. Patients must have a well-defined germline mutation of the transthyretin (TTR) gene
rendering them at risk for amyloidosis, and be free of clinical evidence of SA.
2. All patients in Part 3 will be >50 years of age. There are no gender or racial
restrictions.
3. 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.
4. Subjects must provide signed, written, informed consent and be willing to comply with
eligibility requirements, scheduled visits, and follow-up studies.
5. Due to annual dosimetry limitations, subjects 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.
Prior to participation Part 4 of the trial (n = 5), the following inclusion criteria must
be met:
1. Healthy Control Subjects (HC) will be generally healthy adults, either male or female,
and will not have a diagnosis of amyloidosis, will not have a first- or second-degree
relative (parent, sibling, child, aunt, uncle, niece, nephew) with confirmed or
suspected familial amyloidosis, and will not have diabetes mellitus (type 2).
2. All Part 4 subjects will be > 30 years of age or older.
3. 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.
4. Patients must provide signed, written, informed consent and be willing to comply with
eligibility requirements, scheduled visits, and follow-up studies.
5. Due to annual dosimetry limitations, patients who have participated in another nuclear
medicine imaging clinical trial protocol can be included in this study no earlier than
12 months after the previous radiotracer injection.
Prior to participation in Part 5 of the trial, the following inclusion criteria must be
met:
1. Patients must have successfully completed participation in Part 2 or Part 3 of this
trial with CT/PET images confirming the presence of abnormal amyloid deposits in
thoracoabdominal organs.
2. Patients must have received a 2 mCi dose of 124I-p5+14 Injection during Part 2 or 3 of
this trial with visual evidence of uptake of radiotracer in abdominothoracic organs
associated with amyloid.
3. The repeat exposure to the study agent must occur at least 6 months after the first
exposure.
4. Patients must submit a serum specimen for exploratory evaluation of the presence of
anti-p5+14 peptide antibodies, with results reviewed by the Principal Investigator
prior to a second exposure to the study agent.
5. The patient must meet all of the Inclusion criteria for participation in Part 2 or
Part 3 outlined in Sections 5.2 or Section 5.3 (as applicable), including the signing
of an informed consent for Part 5.
In addition, the following criteria will exclude candidates from participation in the
trial, Parts 1 and 2:
1. Those with significant co-morbidity (e.g., Eastern Cooperative Oncology Group [ECOG]
score of 3 or greater), uncontrolled infection, or other serious illness.
2. Patients with a sustained SpO2 of = 92% as noted in the medical record.
3. Patients that require renal dialysis.
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) who test
positive for pregnancy in a laboratory test administered by the site physician, are
pregnant, or are nursing
5. Patients who have received any amyloidophilic radiotracer as part of a research
clinical trial (not standard of care) 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 or iOSAT iodine treatment.
The following criteria will exclude candidates from participation in Part 3 of the trial:
1. Those with significant co-morbidity (e.g., Eastern Cooperative Oncology Group [ECOG]
score of 3 or greater), uncontrolled infection, or other serious illness.
2. Subjects with a sustained SpO2 of = 92% as noted in the medical record.
3. 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) who test
positive for pregnancy in a laboratory test administered by the site physician, are
pregnant, or are nursing.
4. Subjects who have clinical evidence of amyloidosis based on standard clinical
criteria.
5. Subjects with polyneuropathy of unknown origin.
6. Subjects who have received any amyloidophilic radiotracer as part of a research
clinical trial (not standard of care) within the past 12 months.
7. Subjects with exposure to heparin, or heparin-based medications, within 7 days prior
to the imaging study.
8. Subjects who have a known allergy to acetaminophen or iOSAT iodine treatment.
9. Subjects with clinical signs of SA based on routine investigation of serum and urine
biomarkers, radiographic or nuclear imaging studies, or peripheral nerve evaluations.
The following criteria will exclude subjects from participation in Part 4:
1. Those with significant co-morbidity (e.g., Eastern Cooperative Oncology Group [ECOG]
score of 2 (Restricted in physically strenuous activity but ambulatory and able to
carry out work of a light or sedentary nature, e.g. light house work, office work) or
greater), uncontrolled infection, or other serious illness.
2. Individuals with a sustained SpO2 of = 92% as noted in the medical record.
3. 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) who test
positive for pregnancy in a laboratory test administered by the site physician, are
pregnant, or are nursing.
4. Subjects who have received any amyloidophilic radiotracer as part of a research
clinical trial (not standard of care) within the past 12 months.
5. Subjects with exposure to heparin, or heparin-based medications, within 30 days prior
to the imaging study.
6. Subjects who have a known allergy to acetaminophen or iOSAT iodine treatment.
7. Subjects with a diagnosis of Type 2 diabetes mellitus or who are taking medication for
management of Type 2 diabetes mellitus.
8. Active infection requiring systemic antiviral or antimicrobial therapy that will not
be completed prior to Study Day 1.
9. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C
or chronic hepatitis.
10. Uncontrolled hypertension (BP > 160/100 mm Hg).
11. Smokes >20 cigarettes a day.
12. A diagnosis of heart failure with preserved ejection fraction.
13. Has any other conditions, which, in the opinion of the Investigator would make the
subject unsuitable for inclusion, or could interfere with the subject participating in
or completing the study
The following criteria will exclude subjects from participation in Part 5.
1. Any patient who experienced a clinically significant adverse event related to prior
exposure to the study agent.
2. Any subject who meets any of the Exclusion Criteria for Part 2 or Part 3 (as
applicable), described in Section 5.3.1 and Section 5.3.2.
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