Evaluation of PET Probe [64]Cu-Macrin in Cardiovascular Disease, Cancer and Sarcoidosis.

• ClinicalTrials.gov Identifier: NCT04843891
• Recruitment Status: Recruiting
• First Posted: April 14, 2021
• Last Update Posted: June 23, 2022
• Sponsor: Ralph Weissleder, MD
• Information provided by (Responsible Party): Ralph Weissleder, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: March 31, 2021
• First Posted Date: April 14, 2021
• Last Update Posted Date: June 23, 2022
• Actual Study Start Date: September 6, 2021
• Estimated Primary Completion Date: April 5, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 8, 2021)

• To establish human dosimetry of 64Cu Macrin in Healthy Volunteers [ Time Frame: 1 year ]
  We will use established methods to provide quantitative information on the amount of [64Cu] Macrin radioactivity that accumulates in peripheral organs and brain. Dose-corrected imaging data will be processed using time-activity curves based on ROIs manually-drawn on MR data and projected onto PET datasets.
• [64Cu] Macrin accumulation and detection in cancer [ Time Frame: 1 year ]
  Probe uptake will be measured in organs affected by solid epithelial malignancies and compared to uptake in the uninvolved parts of the organs and in these organs in healthy volunteers. We expect greater uptake in the part of the organs affected by malignancy.
• [64Cu] Macrin accumulation and detection in myocardial infarction [ Time Frame: 1 year ]
  Probe uptake will be measured at a myocardial infarct and compared to uptake in the remainder of the heart and in the hearts of healthy volunteers. We expect greater uptake at the site of a myocardial infarction.
• [64Cu] Macrin accumulation and detection in sarcoidosis [ Time Frame: 1 year ]
  Probe uptake will be measured in the heart and lungs of patients with sarcoidosis and compared to uptake in these organs in healthy volunteers. We expect greater uptake in the organs affected by sarcoidosis.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 8, 2021)

[64Cu] Macrin accuracy for macrophage localization [ Time Frame: 1 year ]

To determine the sensitivity and specificity of [64 Cu] Macrin accumulation for the detection at sites of inflammation by comparing tracer accumulation to histopathology and/or standard of care imaging studies

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of PET Probe [64]Cu-Macrin in Cardiovascular Disease, Cancer and Sarcoidosis.
• Official Title: Preliminary Evaluation of [64Cu] Macrin in Healthy Individuals and Subjects With Cardiovascular Disease, Sarcoidosis and Malignancy.
• Brief Summary: To evaluate the safety of [64Cu] Macrin and its whole-body distribution, metabolism, pharmacokinetics, and radiation burden in healthy volunteers. To detect [64Cu]-Macrin accumulation in sites of disease in subjects with cancer, sarcoidosis or myocardial infarct.

Detailed Description

Macrophages are phagocytic cells of the innate immune system. Their accumulation is a hallmark of many inflammatory diseases and they have diverse roles in tissue responses to infection and injury and in tissue repair. As macrophages have a tissue specific and often disease stage specific roles, future therapies directed at macrophage subtypes at certain points in the course of a disease may be more efficacious and result in less systemic side effects, as compared to conventional chemotherapeutics. [64Cu] Macrin is designed to detect macrophages by PET imaging. As a result, PET imaging can be used to identify inflammatory "hotspots" and quantitate local macrophage density non-invasively. The investigators studies in mice showed that [64Cu] Macrin has excellent pharmacological and pharmacokinetic profile with high target uptake and low retention in background tissues and organs.

The investigators wish to first evaluate in healthy human subjects the pharmacological and pharmacokinetic profile, and the overall safety of the new radiopharmaceutical [64Cu] Macrin. The investigators will then establish the concentration of [64Cu] Macrin in patients following myocardial infarct, in sarcoidosis and in cancer patients. In a subset of patients where tissue sampling is feasible, we will correlate tracer uptake on imaging to macrophage density on histopathology or with additional standard of care imaging studies.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

Eligible subjects, including healthy volunteers and patients with sarcoidosis, cardiovascular disease and cancer, will be enrolled to undergo imaging with the PET Probe [64]Cu Macrin

Masking: None (Open Label)
Primary Purpose: Diagnostic

Condition

• Sarcoid
• Cardiovascular Diseases
• Cancer

Intervention

Drug: [64]Cu Macrin

Up to 15 mCi of [68Ga]CBP8 will be administered to each subject.

Study Arms

• Experimental: Healthy Volunteers
  In 10 healthy volunteers the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied.
  Intervention: Drug: [64]Cu Macrin
• Experimental: Cardiovascular Disease
  In 30 subjects with a history of recent myocardial infarct, the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied. In addition, the ability of [64Cu] Macrin to concentrate at the infarct site will be correlated with cardiac MRI.
  Intervention: Drug: [64]Cu Macrin
• Experimental: Cancer
  In 30 subjects with an epithelial malignancy the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied. In addition, the ability of [64Cu] Macrin to concentrate at the tumor site will be correlated with imaging and histopathology, where available.
  Intervention: Drug: [64]Cu Macrin
• Experimental: Sarcoidosis
  In 30 subjects with sarcoidosis the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied. In addition, the ability of [64Cu] Macrin to concentrate at the tumor site will be correlated with imaging and histopathology, where available.
  Intervention: Drug: [64]Cu Macrin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 8, 2021): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 5, 2023
• Estimated Primary Completion Date: April 5, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Group 1: Healthy subjects

• Must be 18 years of age or older

• Must be deemed healthy at screening visit, as determined by the physician investigator or nurse practitioner, based on the following assessments at screening: physical examination, medical history and vital signs;

  • No known history of pre-existing cardiac or respiratory disease or malignancy
  • Have the ability to give written informed consent.

Group 2: Myocardial Infarction

• History of percutaneous coronary intervention (PCI) for acute or chronic coronary syndrome (within 3-5 days)
• Have the ability to give written informed consent
• Must be 18 years of age or older
• Hemodynamically stable

Group 3: Sarcoidosis

• A suspected or confirmed diagnosis of intrathoracic sarcoidosis
• Have the ability to give written informed consent
• Must be 18 years of age or older

Group 4: Malignancy

• Suspected or confirmed thoracic, intra-abdominal or pelvic malignancy
• Have the ability to give written informed consent
• Must be 18 years of age or older

Exclusion Criteria:

• • Electrical implants, such as cardiac pacemaker or perfusion pump;

  • Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, or steel implants ferromagnetic objects such as jewelry or metal clips in clothing;
  • eGFR of less than 30 mL/min/1.73 m2 within the past 30 days;
  • Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate);
  • Self-reported or documented claustrophobic reactions;
  • Research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);
  • Unable to lie comfortably on a bed inside the MR-PET;
  • BMI > 33 (limit of the PET-MRI table);
  • Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures);
  • Stroke within the last 3 months;
  • Cardiac or major surgery within the last 3 months;
  • History of abnormal heart rate including persistent tachyarrhythmia (heart rate persistently >120 bpm) or bradyarrhythmia (heart rate persistently < 50 bpm);
  • History of atrial premature complexes with daytime pauses > 3s;
  • Contraindications to gadolinium-based contrast agents, including an eGFR < 30 mL/min (myocardial infarction and sarcoidosis patients only).
  • History of myeloproliferative disorder.
  • Age >80 years.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04843891
• Other Study ID Numbers: 2021P000355
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ralph Weissleder, MD, Massachusetts General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Ralph Weissleder, MD
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Massachusetts General Hospital
• Verification Date: June 2022