A Phase 1 Study of 99mTc-p5+14 in Healthy Volunteers and Patients With AL or ATTR Systemic Amyloidosis

NCT05951816 | Unknown Phase 1 FDA Drug

• 1 other identifier: UTGSM-164388-101
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Amyloidosis

Keywords

Amyloidosis; p5+14; SPECT imaging; iodine-124-evuzamitide

Outcome Measures

Primary Outcomes (1)

• Whole body effective dosimetry measurement

  Whole body effective radiation dose assessed from analysis of organ-specific radioactivity uptake in planar and SPECT images.

  From enrollment to the end of study is 8 days

Secondary Outcomes (2)

• 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

• 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

Other Outcomes (1)

• 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

Study Arms (2)

Estimation of dosimetry for 99mTc-p5+14 and Biodistribution Of 99mtc-p5+14 In Healthy Subjects

EXPERIMENTAL

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.

Biodistribution in patients with systemic AL or ATTR amlyoidosis

EXPERIMENTAL

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.

Interventions

99mTc-p5+14 is an amyloid reactive peptide labeled with technetium-99m. DRUG

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.

Estimation of dosimetry for 99mTc-p5+14 and Biodistribution Of 99mtc-p5+14 In Healthy Subjects

99mTc-Pyrophosphate and 99mtc-p5+14 - an Amyloid Reactive Peptide Labeled With Technetium-99m. DRUG

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.

Also known as: 99mTc-PYP

Biodistribution in patients with systemic AL or ATTR amlyoidosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PART 1
• Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
• Be male or female \>18 years of age.
• 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.
• 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.
• 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.
• Have a diagnosis of cardiac amyloidosis within 2 years of screening. PART 2
• \) Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
• \) 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.
• \) 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.
• \) Have one of the following:
• 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.
• 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.
• Have a diagnosis of cardiac amyloidosis within 2 years of screening. PART 3
• Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.

You may not qualify if:

• PARTS 1-4
• 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.
• Is pregnant or breast-feeding.
• Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis.
• Has a known allergy to potassium iodide.
• Receiving hemodialysis or peritoneal dialysis.
• Has severe claustrophobia or any medical condition that would prevent completion of the imaging protocol.
• Has any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.
• Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within seven (7) days prior to 99mTc-p5+14 administration.
• Have previously received any dose of p5+14, in any form.
• Have a QTc interval, using Bazett's formula (QTcB) of \>480 ms, measured within six months prior to enrollment, or assessed prior to injection.
• 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.
• 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.

Sponsors & Collaborators

• University of Tennessee Graduate School of Medicine: lead
• Attralus, Inc.: collaborator

Study Sites (1)

University of Tennessee Graduate School of Medicine

Knoxville, Tennessee, 37920, United States

RECRUITING

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Amyloidosis

Interventions

Technetium; Technetium Tc 99m Pyrophosphate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Elements, Radioactive; Elements; Inorganic Chemicals; Metals, Heavy; Transition Elements; Radioisotopes; Isotopes; Metals; Diphosphates; Polyphosphates; Phosphates; Phosphoric Acids; Phosphorus Acids; Acids, Noncarboxylic; Acids; Phosphorus Compounds; Technetium Compounds

Study Officials

• Jonathan S Wall, PhD

  University of Tennessee Graduate School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily B Martin, PhD

CONTACT

865-305-9533; emartin@utmck.edu

Study Design

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

Study Record Dates

• First Submitted: June 30, 2023
• First Posted: July 19, 2023
• Study Start: July 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: July 19, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)