A Phase 1 Study of 99mTc-p5+14 in Healthy Volunteers and Patients With AL or ATTR Systemic Amyloidosis
Study Details
Study Description
Brief Summary
This study will investigate 99mTc-p5+14, an amyloid-reactive synthetic peptide, p5+14, radiolabeled with technetium-99m, as a radiotracer for detecting paamyloid deposits in patients with AL or ATTR-associated systemic amyloidosis, notably with cardiac involvement.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1 |
Detailed Description
The University of Tennessee Graduate School of Medicine (UTGSM) is investigating 99mTc-p5+14, an amyloid-reactive synthetic peptide, p5+14, radiolabeled with technetium-99m, as a radiotracer for planar gamma scintigraphy (PGS), single photon emission computed tomography (SPECT) or SPECT with x-ray computed tomography (SPECT/CT) for the diagnosis of systemic amyloidosis, notably with cardiac involvement. Based on nonclinical data and clinical data of 124I-p5+14 from Study AMY1001, peptide p5+14 binds many types of human amyloid and is rapidly cleared from the central compartment. When radiolabeled with 99mTc, p5+14 may enable visualization of amyloid laden tissues and organs by SPECT/CT imaging or PGS. Thus, this study has been designed to evaluate the dosimetry and biodistribution of 99mTc-p5+14 in patients with systemic amyloidosis compared with the biodistribution in healthy volunteers.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Estimation of dosimetry for 99mTc-p5+14 and Biodistribution Of 99mtc-p5+14 In Healthy Subjects For dosimetry, patients with a confirmed diagnosis of systemic AL amyloidosis, patients will be administered a single IV dose of up to 1 mg of 99mTc-p5+14 (~20 mCi) by slow push (~1 mL/5 sec.). Patients will then undergo serial planar scintigraphic imaging at ~30 minutes, ~1 hour, ~2 hours, ~4 hours, ~6 hours, and ~24 hours post-injection. At the 4-hour time point, the patient will also undergo a single SPECT/CT scan to provide additional data for estimating dosimetry. Before injection of the radiotracer and at each imaging session, ~2 -3 mL of blood will be acquired to determine the whole blood radioactivity. Healthy volunteers will undergo an echo examination, thereafter, they will be administered a single IV dose of 99mTc-p5+14 (20 mCi) and will undergo a single planar image acquisition followed by SPECT/CT imaging at ~1 hour and ~3 hours post-injection. |
Drug: 99mTc-p5+14 is an amyloid reactive peptide labeled with technetium-99m.
Peptide p5+14 is a pan-amyloid reactive, synthetic 45 L-amino acid polypeptide with a net +12 positive charge that can bind two major components of all extracellular amyloid deposits: (i) hypersulfated heparan sulfate glycosaminoglycans (proteoglycans) and (ii) amyloid fibrils. The polypeptide, labeled with iodine-124, has been shown (study AMY1001) to bind amyloid in all organs including the heart. This study will evaluate a Tc-99m-labeled version of the peptide for gamma imaging.
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| Experimental: Biodistribution in patients with systemic AL or ATTR amlyoidosis Patients with a confirmed diagnosis of systemic AL or ATTR (with or without a positive PyP scan) will be administered a single IV dose of up to 1 mg of 99mTc-p5+14 (~20 mCi) by slow push (~1 mL/5 sec.). At ~1 hour and ~3 hours post-injection, patients will undergo abdominothoracic planar imaging followed by SPECT/CT imaging covering the same area. Vital signs (blood pressure, respiration rate, temperature, and pulse) will be acquired before injection of the 99mTc-p5+14, and at ~3 hours post injection. On Day 3, patient will undergo a trans thoracic echo examination. On Day 4, patients will undergo Technescan™ 99mTc-PYP (20 mCi) planar and SPECT/CT imaging at ~1 hour and ~3 hours post-injection. Vital signs (blood pressure, respiration rate, temperature, and pulse) will be acquired before injection of the 99mPYP, and at ~3 hours post injection. |
Drug: 99mTc-Pyrophosphate and 99mtc-p5+14 - an Amyloid Reactive Peptide Labeled With Technetium-99m.
99mTc-PYP is an FDA-approved, commercially available bone-seeking radiotracer used routinely in nuclear medicine. 99mTC-PYP imaging is used clinically for the diagnosis of cardiac ATTR amyloidosis.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Whole body effective dosimetry measurement [From enrollment to the end of study is 8 days]
Whole body effective radiation dose assessed from analysis of organ-specific radioactivity uptake in planar and SPECT images.
Secondary Outcome Measures
- Measure cardiac uptake of 99mTc-p5+14 radioactivity from planar and SPECT/CT images in comparison to 99mTc-PYP uptake [From enrollment to the end of study is 8 days]
Measurement of 99mTc-p5+14 uptake in the heart of healthy volunteers and patients with systemic AL or ATTR amyloidosis and comparison with contemporaneous 99mTc-PYP cardiac radioactivity.
- Measure uptake of 99mTc-p5+14 radioactivity in extracardiac tissues from planar and SPECT/CT images [From enrollment to the end of study is 8 days]
Measurement of 99mTc-p5+14 radioactivity in abdominothoracic organs of healthy volunteers and patients with systemic AL or ATTR amyloidosis from planar and SPECT/CT images.
Other Outcome Measures
- Compare planar and SPECT imaging of 99mTc-p5+14 for the detection of cardiac amyloid [From enrollment to the end of study is 8 days]
To compare the quantitative cardiac uptake of 99mTc-p5+14 and 99mTc-PyP in patients with systemic ATTR amyloidosis imaged by planar gamma scitigraphic and SPECT/CT imaging acquired at 1-hour and 3-hour post-injection.
Eligibility Criteria
Criteria
Inclusion Criteria:
PART 1
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Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
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Be male or female >18 years of age.
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Women of child-bearing potential (WOCBP) (those who have not been surgically sterilized, are not postmenopausal [i.e., last menstrual period >2 years ago without pharmaceutical intervention], and women who are fertile) must have a negative pregnancy test prior within 24 h prior to infusion.
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WOCBP who are not exclusively in same-sex relationships and male participants with female sexual partners who are WOCBP must agree to use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, for at least 2.5 days after injection of 99mTc-p5+14.
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Have a confirmed diagnosis of systemic AL amyloidosis based on either a histologic confirmation with a biopsy containing deposits of apple-green birefringent, Congophilic material with aberrant organ-specific biomarkers indicating amyloid involvement, physical examination, or imaging study.
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Have a diagnosis of cardiac amyloidosis within 2 years of screening. PART 2
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Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
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Be male or female >18 years of age. 3) WOCBP (those who have not been surgically sterilized, are not postmenopausal [i.e., last menstrual period > 2 years ago without pharmaceutical intervention], and women who are fertile) must have a negative pregnancy test prior within 24 h prior to infusion.
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WOCBP who are not exclusively in same-sex relationships and male participants with female sexual partners who are WOCBP must agree to use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, for at least 2.5 days after injection of 99mTc-p5+14.
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Have one of the following:
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a confirmed diagnosis of systemic AL amyloidosis, based on either a histologic confirmation of a cardiac or extracardiac biopsy containing deposits of apple-green birefringent, Congophilic material AND imaging parameters (ECHO or CMR) indicative of cardiac involvement.
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a confirmed diagnosis of systemic ATTR amyloidosis, based on either a histologic confirmation of a cardiac biopsy containing deposits of apple-green birefringent, Congophilic material or extracardiac biopsy and imaging parameters (ECHO or CMR or 99mTc-PYP) indicative of cardiac involvement, with no evidence of abnormal serum free light chains.
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Have a diagnosis of cardiac amyloidosis within 2 years of screening. PART 3
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Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
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Be male or female >18 years of age.
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WOCBP (those who have not been surgically sterilized, are not postmenopausal [i.e., last menstrual period > 2 years ago without pharmaceutical intervention], and women who are fertile) must have a negative pregnancy test prior within 24 h prior to infusion.
-
WOCBP who are not exclusively in same-sex relationships and male participants with female sexual partners who are WOCBP must agree to use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, for at least 2.5 days after injection of 99mTc-p5+14.
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Be in good general health, as determined by no clinically significant findings (including Type 2 diabetes mellitus) in the opinion of the Investigator from review of the medical history.
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Does not have a diagnosis of amyloidosis nor has a first- or second-degree relative (parent, sibling, child, aunt, uncle, niece, nephew) with confirmed or suspected familial amyloidosis.
PART 4
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Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
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Be male or female >18 years of age.
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Women of child-bearing potential (those who have not been surgically sterilized, are not postmenopausal [i.e., last menstrual period >2 years ago without pharmaceutical intervention], and women who are fertile) must have a negative pregnancy test prior within 24 h prior to infusion.
-
WOCBP who are not exclusively in same-sex relationships and male participants with female sexual partners who are WOCBP must agree to use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, for at least 2.5 days after injection of 99mTc-p5+14..
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Has a confirmed diagnosis of systemic ATTR amyloidosis, based on either a histologic confirmation of a cardiac biopsy containing deposits of apple-green birefringent, Congophilic material or extracardiac biopsy and imaging parameters (ECHO or CMR), or abnormal serum biomarkers indicative of cardiac involvement, with no evidence of abnormal serum free light chains.
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Has a diagnosis of cardiac amyloidosis within 2 years of screening.
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Has a negative 99mTc-PYP imaging study.
Exclusion Criteria:
PARTS 1-4
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Due to annual dosimetry limitations, patients who have participated in another nuclear medicine amyloid imaging clinical trial protocol and received tracer injection in the last 6 months.
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Is pregnant or breast-feeding.
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Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis.
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Has a known allergy to potassium iodide.
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Receiving hemodialysis or peritoneal dialysis.
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Has severe claustrophobia or any medical condition that would prevent completion of the imaging protocol.
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Has any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.
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Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within seven (7) days prior to 99mTc-p5+14 administration.
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Have previously received any dose of p5+14, in any form.
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Have a QTc interval, using Bazett's formula (QTcB) of >480 ms, measured within six months prior to enrollment, or assessed prior to injection.
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Have a serum AST >2x the upper limit of normal or 80 IU/L AND total bilirubin > 1.5x the upper limit of normal or 1.8 mg/dL within the previous six months of enrollment.
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Have a serum ALT >2x the upper limit of normal or 64 IU/L AND total bilirubin > 1.5x the upper limit of normal or 1.8 mg/dL within the previous six months of enrollment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Tennessee Graduate School of Medicine | Knoxville | Tennessee | United States | 37920 |
Sponsors and Collaborators
- University of Tennessee Graduate School of Medicine
- Attralus, Inc.
Investigators
- Principal Investigator: Jonathan S Wall, PhD, University of Tennessee Graduate School of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UTGSM-164388-101