PET Imaging of Subjects Using 124I-PU-AD

PET Imaging of Subjects Using 124I-PU-AD: A Pilot Study

This is a first in-human, open-label pilot (microdose) study of the positron-emitting agent 124I-PU-AD in subjects with specific cancer types (solid malignancy, lymphoma, and/or myeloma) and/or Alzheimer's disease.

Study Overview

• Status: Terminated
• Conditions: Lymphoma; Alzheimer Disease; Myeloma; Solid Malignancy
• Intervention / Treatment: Drug: PU-AD; Device: PET Scan; Other: Blood Draws

Detailed Description

This first in-human trial of the positron-emitting agent 124I-PU-AD is an open-label pilot (microdose) study. Up to 10 evaluable subjects who have active disease will be enrolled to evaluate the PK, metabolism, biodistribution, and radiation dosimetry of 124I-PU-AD.

Following a 28-day screening period, eligible subjects will return to the clinic on Day 1. A single dose of 124I-PU-AD will be administered by intravenous (IV) injection to subjects.

After 124I-PU-AD tracer injection, PET scans will be performed at 4 time points. At each time-point, an axial body image is acquired on a state-of-the-art PET-CT scanner. A low-dose CT will be obtained immediately-prior to PET imaging, at each time-point. Serial blood samples will also be obtained at multiple time points.

Subjects will be evaluated to ensure that there are no clinically significant ongoing AEs prior to discharge.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects with a diagnosis of cancer and/or Alzheimer's Disease, meeting trial eligibility criteria as specified below for either disease:

   Cancer:

   1. Subjects with eligible histologic types of cancer. Eligible histologic types of cancer include solid malignancy, myeloma, and lymphoma.
   2. Cancer histology confirmed by pathology.
   3. Cancerous disease is radiologically-measurable or evaluable as defined by published tumor response criteria (including but not limited to RECIST 1.1).

   Alzheimer's:

   1. Established diagnosis of mild-moderate Alzheimer's disease based upon neurological and neuropsychological evaluation following the National Institute on Aging - Alzheimer's disease Association criteria that recently revisited the NINCDS-ADRDA criteria.
   2. Documentation of diagnosis of mild-moderate Alzheimer's disease, as above, by board-certified neurologist.
2. Subjects who have both cancer and Alzheimer's Disease, subjects are considered eligible if they meet all eligibility requirements for either Alzheimer's Disease or cancer patients, as specified above.

Exclusion Criteria:

1. Subject has unacceptable pre-study organ function during screening defined as:

   1. Bilirubin > 1.5 x institutional upper limit of normal (ULN)
   2. AST/ALT >2.5 x ULN
   3. Albumin < 2 g/dl
   4. GGT > 2.5 x ULN (IF Alkaline phosphatase > 2.5 x ULN)
   5. Creatinine >1.5 x ULN or creatinine clearance < 60 mL/min.
2. Subject has history of acute major illness (i.e., unstable cardiovascular condition.)
3. Subject has concurrent participation in any interventional studies within 30 days of first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 124I-PU-AD; A single dose of 124I-PU-AD will be administered by intravenous (IV) injection	Drug: PU-AD; Device: PET Scan; Other: Blood Draws

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic profile of 124I-PU-AD: area under the curve (AUC)	1 week
Pharmacokinetic profile of 124I-PU-AD: maximum plasma concentration (Cmax)	1 week
Pharmacokinetic profile of 124I-PU-AD: trough plasma concentration (Cmin)	1 week
Pharmacokinetic profile of 124I-PU-AD: plasma half-life (T1/2)	1 week
Pharmacokinetic profile of 124I-PU-AD: time to maximum plasma concentration (Tmax)	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Safety of 124I-PU-AD in subjects as assessed by evaluation of the incidence, nature, and severity of adverse events and serious adverse events.	30 days

Collaborators and Investigators

• Sponsor: Samus Therapeutics, Inc.
• Collaborators: Memorial Sloan Kettering Cancer Center; Weill Medical College of Cornell University; Rockefeller University

Publications and helpful links

General Publications

• Bolaender A, Zatorska D, He H, Joshi S, Sharma S, Digwal CS, Patel HJ, Sun W, Imber BS, Ochiana SO, Patel MR, Shrestha L, Shah SK, Wang S, Karimov R, Tao H, Patel PD, Martin AR, Yan P, Panchal P, Almodovar J, Corben A, Rimner A, Ginsberg SD, Lyashchenko S, Burnazi E, Ku A, Kalidindi T, Lee SG, Grkovski M, Beattie BJ, Zanzonico P, Lewis JS, Larson S, Rodina A, Pillarsetty N, Tabar V, Dunphy MP, Taldone T, Shimizu F, Chiosis G. Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system. Nat Commun. 2021 Aug 3;12(1):4669. doi: 10.1038/s41467-021-24821-2.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): June 10, 2019
• Study Completion (Actual): June 10, 2019

Study Registration Dates

• First Submitted: November 29, 2017
• First Submitted That Met QC Criteria: December 11, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: PU-AD-00-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No