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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Whole body effective dosimetry measurement
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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+
- •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
- •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+
- •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.
- •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+
- •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.
- •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+
- •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.
排除标准
- •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.
研究组 & 干预措施
Estimation of dosimetry for 99mTc-p5+14 and Biodistribution Of 99mtc-p5+14 In Healthy Subjects
For dosimetry, healthy subjects (n=3) and patients with a confirmed diagnosis of AL (n=1) or ATTR amyloidosis (n=1) 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.). Subjects 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 subject 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. An echo examination will also be performed.
For physiological biodistribution, healthy volunteers (n=5) will undergo an echo examination, thereafter, they will be administered a single IV dose of 99mTc-p5+14 (20 mCi) and will undergo a planar image acquisition followed by SPECT/CT imaging at ~1 hour and ~3 hours post-injection.
干预措施: 99mTc-p5+14 is an amyloid reactive peptide labeled with technetium-99m. (Drug)
Biodistribution in patients with systemic AL or ATTR amlyoidosis
On Day 1, 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 whole body planar imaging followed by abdominothoracic SPECT/CT imaging. 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. ECG measurements will be made within 1 hour prior to, and within 15 minutes after, 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 99mTc-PYP, and at ~3 hours post injection. ECG measurements will be made as on Day 1.
干预措施: 99mTc-p5+14 is an amyloid reactive peptide labeled with technetium-99m. (Drug)
Biodistribution in patients with systemic AL or ATTR amlyoidosis
On Day 1, 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 whole body planar imaging followed by abdominothoracic SPECT/CT imaging. 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. ECG measurements will be made within 1 hour prior to, and within 15 minutes after, 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 99mTc-PYP, and at ~3 hours post injection. ECG measurements will be made as on Day 1.
干预措施: 99mTc-Pyrophosphate (Drug)
结局指标
主要结局
Whole body effective dosimetry measurement
时间窗: 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.
次要结局
- 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)