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

NCT03678259 | Completed Phase 1 FDA Drug

• 1 other identifier: AMY1001
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Amyloidosis

Keywords

Amyloidosis, AL, ATTR, ALect2

Outcome Measures

Primary Outcomes (1)

• Organ-specific radioactivity dosimetry (Part 1).

  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)

  Through 48 hours

Secondary Outcomes (12)

• Absolute values and changes from baseline in clinical laboratory values.

  Baseline and 24 hours

• Clinically defined amyloidosis organ involvement.

  Baseline

• Measure of background radioactivity uptake.

  6 hours and 24 hours

• Measure of radioactivity uptake by each organ

  6 hours and 24 hours

• Concentration of radiotracer in specific anatomic sites, for each subject and anatomic site

  6 hours and 24 hours

Study Arms (1)

124I-p5+14 Injection

EXPERIMENTAL

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.

Drug: 124I-p5+14 Injection

Interventions

124I-p5+14 Injection DRUG

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

Also known as: APi1832

124I-p5+14 Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects included in this trial are volunteers with a confirmed diagnosis of systemic amyloidosis, a genetically well-defined mutation of the TTR gene but without clinical evidence of active disease, and at an age typical of development of symptomology ≥ 50, or healthy control subjects (≥30 years).
• Patients must have a confirmed diagnosis of systemic amyloidosis, based on either a histologic confirmation that a biopsy contains deposits of apple-green birefringent, Congophilic material or genetic screening and presence of amyloid-related pathology, or amyloid-specific imaging study. Additionally, the type of amyloidosis (AL, ATTR, ALect2, or other) should be characterized.
• Patients enrolled in Part 1 (n = 3) must have widespread AL amyloidosis, defined as biopsy proven or clinically detectable involvement, of at least two organs (excluding the peripheral nervous system).
• All patients in Parts 1 and 2 will be 18 years of age or older. There are no gender or racial restrictions.
• 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.
• Patients who have had or are currently receiving therapy or other drug based anti-amyloid regimens can be included on study (Parts 1 and 2).
• Patients must provide signed, written, informed consent and be willing to comply with eligibility requirements, scheduled visits, and follow-up studies.
• 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.
• Patients must have a well-defined germline mutation of the transthyretin (TTR) gene rendering them at risk for amyloidosis, and be free of clinical evidence of SA.
• All patients in Part 3 will be \>50 years of age. There are no gender or racial restrictions.
• 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.
• Subjects must provide signed, written, informed consent and be willing to comply with eligibility requirements, scheduled visits, and follow-up studies.
• Due to annual dosimetry limitations, subjects 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.
• Healthy Control Subjects (HC) will be generally healthy adults, either male or female, and will not have a diagnosis of amyloidosis, will not have a first- or second-degree relative (parent, sibling, child, aunt, uncle, niece, nephew) with confirmed or suspected familial amyloidosis, and will not have diabetes mellitus (type 2).
• All Part 4 subjects will be \> 30 years of age or older.

Sponsors & Collaborators

• University of Tennessee Graduate School of Medicine: lead

Study Sites (1)

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Related Publications (1)

• Wall JS, Martin EB, Endsley A, Stuckey AC, Williams AD, Powell D, Whittle B, Hall S, Lambeth TR, Julian RR, Stabin M, Lands RH, Kennel SJ. First in Human Evaluation and Dosimetry Calculations for Peptide 124I-p5+14-a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET/CT Imaging. Mol Imaging Biol. 2022 Jun;24(3):479-488. doi: 10.1007/s11307-021-01681-2. Epub 2021 Nov 16.

  PMID: 34786667 DERIVED

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Amyloidosis

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

Study Officials

• Jonathan Wall, Ph.D.

  UTHSC Graduate School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: open-label
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first three patients enrolled in the trial (Part 1) will take part in a dose-escalation 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. The trial then will be opened to include another 54 patients who will receive a single IV bolus injection of 2 mCi 124I-p5+14 Injection. Every patient participating will receive \< 2 mg of peptide p5+14. The study comprises five parts.In Part 2, the trial will enroll SA patients with confirmed AL, ATTR, ALECT2, or other forms of amyloidosis.In Part 3, the trial will study asymptomatic subjects with genetically confirmed mutation of the transthyretin gene.Part 4 will include five healthy control subjects.Part 5 will recruit previously enrolled subjects from Parts 2 or 3 who received a 2 mC dose of 124I-p5+14 Injection and had images confirming the presence of abnormal amyloid deposits for a second exposure to 124I p5+14 Injection and second PET/CT scan.

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: September 19, 2018
• Study Start: October 1, 2018
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: March 25, 2022

Record last verified: 2021-07

Locations

US (1)