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124I-p5+14 Injection Safety in Subjects With Systemic Amyloidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03678259
Recruitment Status : Recruiting
First Posted : September 19, 2018
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
University of Tennessee Graduate School of Medicine

Tracking Information
First Submitted Date  ICMJE July 30, 2018
First Posted Date  ICMJE September 19, 2018
Last Update Posted Date October 3, 2018
Actual Study Start Date  ICMJE October 1, 2018
Estimated Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
Organ-specific radioactivity dosimetry (Part 1). [ Time Frame: Through 48 hours ]
Localization of 124I-p5+14 will be taken from PET/CT images performed at intervals during the 48 hours after injection. Organ-specific dosimetry and whole body dose measurements will be made using Olinda software (Olinda/Exp; Organ Level Internal Dose Assessment/Exponential Modeling)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • Absolute values and changes from baseline in clinical laboratory values. [ Time Frame: Baseline and 24 hours ]
    Laboratory assessments will include hematology and clinical chemistry.
  • Clinically defined amyloidosis organ involvement. [ Time Frame: Baseline ]
    For each subject, the clinician/investigator will designate each organ as involved or not involved with amyloidosis, based on available medical history including prior imaging, prior biopsy results, and clinical laboratory values.
  • Measure of background radioactivity uptake. [ Time Frame: 6 hours and 24 hours ]
    For each subject, a background radioactivity uptake measure will be derived from the PET images at an uninvolved anatomic site (the lumen of a large blood vessel).
  • Measure of radioactivity uptake by each organ [ Time Frame: 6 hours and 24 hours ]
    Uptake of 124I-p5+14 will be derived from PET/CT scans performed at 6 hours and 24 hours after injection. Any organ with >=2-fold higher accumulation of radiotracer, relative to the background uptake, will be considered positive.
  • Concentration of radiotracer in specific anatomic sites, for each subject and anatomic site [ Time Frame: 6 hours and 24 hours ]
    Concentration of 124I-p5+14 will be derived from PET/CT scans performed at 6 hours and 24 hours after injection.
  • Organ and tissue-specific sensitivity of the 124I-p5+14 Injection radiotracer [ Time Frame: 6 hours and 24 hours ]
    Sensitivity for each organ will be derived from the list of clinically involved organs (Secondary Measure 1) and the list of organ radioactivity uptake (Secondary Measure 4), using the formula, true positive rate = [True positive/(True positive + False negative)].
  • Correlation between concentration of the radiotracer (Bq/cc) in the kidney with organ-associated clinical biomarkers. [ Time Frame: 6 hours and 24 hours ]
    Statistical correlation of kidney radiotracer uptake with proteinuria, albuminuria, creatinine, and blood urea nitrogen (BUN).
  • Correlation between concentration of the radiotracer (Bq/cc) in the heart with organ-associated clinical biomarkers. [ Time Frame: 6 hours and 24 hours ]
    Statistical correlation of heart radiotracer uptake with N-terminal-pro-brain natriuretic peptide (NT-BNP) or Brain Natriuretic Peptide (BNP) serum levels, intraventricular septal thickness, and ejection fraction (measures as available from medical history)
  • Peptide uptake in the heart. [ Time Frame: 6 hours and 24 hours ]
    Peptide uptake will be recorded as the Standard Uptake Value (SUV) or as Bq/cc of organ volume; obtained from the Region of Interest (ROI) analysis
  • Peptide uptake in the kidney [ Time Frame: 6 hours and 24 hours ]
    Peptide uptake will be recorded as the Standard Uptake Value (SUV) or as Bq/cc of organ volume; obtained from the Region of Interest (ROI) analysis.
  • Peptide uptake in organ(s) other than kidney or heart if clinically relevant [ Time Frame: 6 hours and 24 hours ]
    Peptide uptake will be recorded as the Standard Uptake Value (SUV) or as Bq/cc of organ volume; obtained from the Region of Interest (ROI) analysis
  • Correlation between uptake of peptide and clinical status of kidney, heart and other organs [ Time Frame: Baseline and 24 hours ]
    Correlation between uptake of peptide (from ROI measurements) and the clinical status of kidney, heart, and other organs if indicated (clinical status defined as in Secondary Endpoint 1).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 124I-p5+14 Injection Safety in Subjects With Systemic Amyloidosis
Official Title  ICMJE Evaluation of 124I-p5+14 Injection as an Imaging Agent for the Detection of Systemic Amyloidosis
Brief Summary This is a single-center, exploratory, Phase 1 Positron Emission Tomography/x-ray Computed Tomography (PET/CT) imaging study to detect amyloidosis that will enroll patients with a confirmed diagnosis of systemic amyloidosis. The purpose of this exploratory trial is to assess the safety and efficacy of 124I-p5+14 Injection at a single-injection dose adequate for imaging amyloid deposits by using PET/CT imaging in subjects with confirmed systemic Immunoglobulin Light Chain-associated Amyloidosis (AL), Transthyretin-associated Amyloidosis (ATTR), Leukocyte Chemotactic Factor 2-associated Amyloidosis (ALect2) as well as other types.
Detailed Description

The rationale for this study is the discovery of a synthetic polypeptide, designated p5+14, a synthetic 45 amino acid peptide that binds many forms of amyloid, including human AL-, ATTR- and ALect2-associated amyloid, as well as human and murine serum amyloid protein A-associated (AA) amyloid. In preclinical studies, using SPECT and PET imaging, as well as microautoradiography, it has been shown that radioiodinated p5+14 binds rapidly and specifically to all amyloid deposits in abdominothoracic organs and tissues.

This is a single site, exploratory, open-label Phase I PET/CT imaging and dosimetry study. The investigational drug product (designated 124I-p5+14 Injection) is an amyloid-reactive synthetic peptide, p5+14 (also known as APi1832), radiolabeled with iodine-124 (I-124 or 124I). All patients enrolled in this exploratory trial will be outpatients with a confirmed diagnosis of systemic amyloidosis.

The first three patients enrolled in the trial (Part 1) will take part in a dose-escalation dosimetry study and will receive a single intravenous (IV) dose of 11.1 Megabecquerel (MBq) (0.3 millicuries (mCi); n = 1), 37 MBq (1 mCi; n = 1) or 74 MBq (2 mCi; n = 1) of 124I-p5+14 Injection for the purpose of determining estimates of organ-associated and whole body radioactive dosimetry. Thereafter, the trial will be opened to include another 40 patients who will be administered a single IV bolus injection of 124I-p5+14 Injection at a dose, to be determined in Part 1 of the study, based on the dosimetry data. Likely, 2 mCi will be used. Every patient participating will receive < 2 mg of peptide p5+14

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
The first three patients enrolled in the trial (Part 1) will take part in a dose-escalation dosimetry study and will receive a single IV dose 11.1 MBq (0.3 mCi; n = 1), 37 MBq (1 mCi; n = 1) or 74 MBq (2 mCi; n = 1) of 124I-p5+14 Injection for the purpose of determining estimates of organ-related and whole body radioactive dosimetry. Thereafter, the trial will be opened to include another 40 patients who will be administered a single IV bolus injection of 124I-p5+14 Injection at a dose, to be determined in Part 1 of the study, based on the dosimetry data. Likely, 2 mCi will be used. Every patient participating will receive < 2 mg of peptide p5+14
Masking: None (Open Label)
Masking Description:
open-label
Primary Purpose: Diagnostic
Condition  ICMJE Systemic Amyloidosis
Intervention  ICMJE Drug: 124I-p5+14 Injection
124I-p5+14 Injection which is a formulation of a synthetic, all natural, 45 amino acid peptide (MW = 4766.4) with a net +12 positive charge
Other Name: APi1832
Study Arms  ICMJE Experimental: 124I-p5+14 Injection
A single-injection dose of 124I-p5+14 adequate for imaging amyloid deposits by using PET/CT imaging in subjects with confirmed systemic amyloidosis of several sub-types.
Intervention: Drug: 124I-p5+14 Injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 17, 2018)
43
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2021
Estimated Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Patients must have a confirmed diagnosis of systemic amyloidosis, based on histologic confirmation that a biopsy contains deposits of apple-green birefringent, Congophilic material. Additionally, the type of amyloidosis (AL, ATTR, ALect2, or other) should be characterized.
  • 2. Patients enrolled in Part 1 must have widespread AL amyloidosis, defined as biopsy proven or clinically detectable involvement, of at least two organs (excluding the peripheral nervous system).
  • 3. All patients will be 18 years of age or older, and there are no gender or racial restrictions.
  • 4. Women of child bearing potential (those who have not been surgically sterilized, are not postmenopausal [typically understood to mean last menstrual period >2 y ago without pharmaceutical intervention], and women who are fertile) must test negative for pregnancy in a laboratory test administered by the site physician.
  • 5. Patients who have had or are currently receiving therapy or other drug-based anti-amyloid regimens can be included on study.
  • 6. Patients must provide signed, written, informed consent and be willing to comply with eligibility requirements, scheduled visits, and follow-up studies.
  • 7. Due to annual dosimetry limitations, patients who have participated in another nuclear medicine amyloid imaging clinical trial protocol can be included in this study no earlier than 12 months after the previous radiotracer injection.
  • 8. Inclusion of patients with amyloid subsets: AL, ATTR, and ALect2 will continue until the trial has achieved recruitment goals for each subset: 20 AL; 10 ATTR; 5 ALect2; and 5 "Other".

Exclusion Criteria:

-1. Individuals with significant cardiac dysfunction (New York Heart Association class IV - "Unable to carry on any physical activity without shortness of breath or angina.

Shortness of breath at rest. If any physical activity is undertaken, discomfort increases") or renal insufficiency that requires dialysis.

  • 2. Those with significant co-morbidity (e.g., Eastern Cooperative Oncology Group (ECOG) score of 3 or greater), uncontrolled infection, or other serious illness.
  • 3. Patients with an Saturation of Peripheral Oxygen (SpO2) of ≤ 92% as noted in the medical record.
  • 4. Women who are of child bearing potential (those who have not been surgically sterilized, are not postmenopausal [typically understood to mean last menstrual period >2 y ago without pharmaceutical intervention], and women who are fertile), are pregnant, or are nursing. Women who test positive for pregnancy in a laboratory test administered by the site physician.
  • 5. Patients who have received any amyloidophilic radiotracer within the past 12 months.
  • 6. Patients with exposure to heparin, or heparin-based medications, within 7 days prior to the imaging study.
  • 7. Patients who have a known allergy to acetaminophen, Benadryl, or iOSAT iodine treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jonathan Wall, Ph.D. 865-305-5447 jwall@utmck.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03678259
Other Study ID Numbers  ICMJE AMY1001
Has Data Monitoring Committee No
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  ICMJE
Plan to Share IPD: Undecided
Responsible Party University of Tennessee Graduate School of Medicine
Study Sponsor  ICMJE University of Tennessee Graduate School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jonathan Wall, Ph.D. UTHSC Graduate School of Medicine
PRS Account University of Tennessee Graduate School of Medicine
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP