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

Официальное название

Phase 1 Study to Investigate the Dosimetry and Biodistribution of a Single Intravenous Administration of 99mTc-p5+14 Using SPECT/CT Imaging and Planar Gamma Scintigraphy in Healthy Volunteers and Patients With AL or ATTR Systemic Amyloidosis

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 99mTc-Pyrophosphate
  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.

Первичные конечные точки

• Whole body effective dosimetry measurement [Срок оценки: From enrollment to the end of study is 8 days]

Вторичные конечные точки (2)

• Measure cardiac uptake of 99mTc-p5+14 radioactivity from planar and SPECT/CT images in comparison to 99mTc-PYP uptake [Срок оценки: 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 [Срок оценки: From enrollment to the end of study is 8 days]

Критерии участия

Критерии включения

PART 1

1\) Understand the study procedures and agree to participate in the study by giving written informed consent..

2\) Be male or female >18 years of age. 3) 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.

4\) 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.

5\) Be a healthy volunteer (n=3) or have a confirmed diagnosis of systemic amyloidosis (n=2) 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.

6\) Healthy volunteers must also meet inclusion criteria for Part 3. PART 2

• Understand the study procedures and agree to participate in the study by giving written informed consent.
• Be male or female >18 years of age.
• 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 4 years of screening, or longer if contemporaneous clinical data indicates the persistent presence of cardiac amyloidosis.

PART 3

• Understand the study procedures and agree to participate in the study by giving written informed consent.
• Be male or female >18 years of age.
• 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.
• 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.
• 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

• Understand the study procedures and agree to participate in the study by giving written informed consent.
• Be male or female >18 years of age.
• 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.
• 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.
• Has a diagnosis of cardiac amyloidosis within 4 years of screening, or longer if contemporaneous clinical data indicates the persistent presence of cardiac amyloidosis.
• Has a negative 99mTc-PYP imaging study.

Критерии исключения

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.
• 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 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.
• Have a QTc interval, using Bazett's formula (QTcB) of >530 ms, measured within six months prior to enrollment, or assessed prior to injection.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

США · 1 центр

• University of Tennessee Graduate School of Medicine — Knoxville

Идентификаторы

NCT: NCT05951816 · UTGSM-164388-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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