First-in-Human Evaluation of an Astrocytic Glutamate Transporter (EAAT2) PET Tracer in Dementia

NCT05374278 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 13180640
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first in human study that will assess the safety and diagnostic performance of \[18F\]RP-115 (fluorine-18 labeled RP115), a positron emission tomography (PET) agent. This agent has the potential to identify the early changes that occur in the brains of patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD).

Conditions

Alzheimer Disease; Frontotemporal Dementia; Dementia

Keywords

Alzheimer Disease; Nuclear medicine; Positron emission tomography; Magnetic resonance imaging; Frontotemporal Dementia

Outcome Measures

Primary Outcomes (3)

• Safety of Administered dose

  Each study participant will undergo a physical examination, vital signs, and ECGs prior to and after the scan and will also be monitored during the scan for adverse events. Additionally, a follow-up with the subject will be conducted 24-48 hours after \[18F\]RP-115 administration. Outcome Measure: Any adverse events will be recorded and graded according to Common Terminology Criteria for Adverse Events.

  A year

• Dosimetry of [18F]RP-115

  Whole-body PET/MRI scan will be conducted immediately after an \[18F\]RP-115 injection and last about 3.5 hours (including breaks) in 8 healthy volunteers (male and female). Equivalent organ radiation doses will be calculated in selected organs using the dynamic PET/MRI data in order to calculate the dosimetry of the tracer. Outcome Measure: Radiation exposure per organ as milliSievert/kg

  A year

• Biodistribution of [18F]RP-115

  Whole-body PET/MRI scan will be conducted immediately after an \[18F\]RP-115 injection and last about 3.5 hours (including breaks) in 8 healthy volunteers (male and female). Percent injected activity (%IA) will be calculated in selected organs using the dynamic PET/MRI data in order to calculate the biodistribution of the tracer. Outcome Measure: Percent injected activity (%Injected radioactivity) in selected organs.

  A year

Secondary Outcomes (1)

• [18F]RP-115 diagnostic performance

  Three years

Study Arms (4)

Cohort 1 - dosimetry of [18F]RP-115 in healthy volunteers

EXPERIMENTAL

Establish \[18F\]RP-115 safety in the clinic with male and female PET imaging.

Drug: [18F]RP-115 PET/MRI or PET/CT and MRI

Cohort 2B - [18F]RP-115 in patients with AD

EXPERIMENTAL

Comparison of \[18F\]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD

Drug: [18F]RP-115 PET/MRI or PET/CT and MRI

Cohort 2C - [18F]RP-115 in patients with FTD

EXPERIMENTAL

Comparison of \[18F\]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD

Drug: [18F]RP-115 PET/MRI or PET/CT and MRI

Cohort 2A - [18F]RP-115 in age-matched controls

EXPERIMENTAL

Comparison of \[18F\]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD

Drug: [18F]RP-115 PET/MRI or PET/CT and MRI

Interventions

[18F]RP-115 PET/MRI or PET/CT and MRI DRUG

An I.V. bolus injection of up to 10 millicurie (mCi) \[18F\]RP-115 will be administered, followed by a PET/MRI scan or by a combination of PET/CT and MRI

Cohort 1 - dosimetry of [18F]RP-115 in healthy volunteers; Cohort 2A - [18F]RP-115 in age-matched controls; Cohort 2B - [18F]RP-115 in patients with AD; Cohort 2C - [18F]RP-115 in patients with FTD

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-75
• Age-suitable BMI
• Ability to provide written informed consent and willingly comply with protocol requirements or has a legal authorized representative/guardian who provides surrogate informed consent.
• No apparent physical disorder.
• Radial, ulnar, or brachial artery suitable for catheterization.
• Non-smoker, and not taking OTC nicotine cessation - to limit peripheral metabolism events.
• Devoid of CNS prescription drugs for three weeks - to limit peripheral metabolism events.
• For Cohort 2B and 2C:
• Must have a study partner (informant) who spends a minimum average of 5 hours per week with the participant (e.g. family member, significant other, friend, caregiver), is generally aware of the participant's daily activities, can provide information about the participant's cognitive and functional performance, and will accompany the participant in all study procedure.
• Recent (within 6 mo.) MME clinical scores.

You may not qualify if:

• Unable to provide written informed consent and unwilling to comply with protocol requirements, or does not have a legal authorized representative/guardian who can provide surrogate informed consent.
• Inadequate arterial access.
• Receipt of radioisotope \< 5 half-lives within \[18F\]RP-115 imaging- as to not confound any scans with radiation background for previous scanning, and unsuitable organ dosimetry thresholds from previous (\> two weeks) PET scans.
• The performed \[18F\]RP-115 scan(s) must not represent \> 3 PET studies total within one year.
• Contra-indication to magnetic resonance, including permanent pacemaker, implantable metallic device, etc.; or severe claustrophobia.
• Participants who are pregnant (female patients of childbearing age will be tested prior to injection of tracer- positive test excludes from the study)
• Participants who are breast-feeding.
• Have a medical condition or other circumstances that in the opinion of the project physicians would significantly decrease chances of obtaining reliable data, achieving the study objective or completing the study.

Sponsors & Collaborators

• David Wilson: lead
• Rio pharmaceuticals Inc.: collaborator

Study Sites (1)

China Basin, UCSF

San Francisco, California, 94107, United States

RECRUITING

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MeSH Terms

Conditions

Alzheimer Disease; Frontotemporal Dementia; Dementia

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• David Wilson, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Wilson, MD, PhD

CONTACT

415-514-6229; david.m.wilson@ucsf.edu

Henry Vanbrocklin, PhD

CONTACT

415-353-4569; henry.vanbrocklin@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Radiology

Study Record Dates

• First Submitted: December 24, 2021
• First Posted: May 16, 2022
• Study Start: November 2, 2021
• Primary Completion (Estimated): April 3, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Anyone who wishes to access the data

Locations

US (1)