Longitudinal Evaluation of [18F]GTP1 as a PET Radioligand for Imaging Tau in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants

NCT02640092 | Completed Phase 1

• 2 other identifiers: GN30009G0097
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 16

Brief Summary

This is an open-label, longitudinal observational study evaluating the imaging characteristics of the tau positron-emission tomography (PET) radioligand \[18F\] Genentech Tau Probe 1 (GTP1) in the brain of participants with prodromal, mild, and moderate Alzheimer's disease (AD) compared to healthy participants. The overall goal of this protocol is to evaluate the longitudinal change in tau burden using \[18F\]GTP1, a tau targeted radiopharmaceutical.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Change in Standardized Uptake Value Ratio (SUVR) as Measured by [18F]GTP1

  From Baseline to 18 months

Secondary Outcomes (5)

• Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)13

  From Baseline to 18 months

• Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Volumetric Magnetic Resonance Imaging (MRI) Measures

  From Baseline to 18 months

• Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Cerebrospinal Fluid (CSF) Markers

  From Baseline to 18 months

• Percentage of Participants With Adverse Events (AEs)

  From Baseline to 18 months

• Test-Retest Variability Based on [18F]GTP1 PET Scans

  From date of test scan to 7-21 days after test scan

Study Arms (1)

[18F]GTP1

EXPERIMENTAL

Participants will complete \[18F\]GTP1 PET imaging at four time points: Baseline, 6 months, 12 months and 18 months. For each \[18F\]GTP1 imaging session, the following procedure will be performed: a catheter will be placed for intravenous (IV) administration of \[18F\]GTP1. Participants will receive an IV bolus injection of up to 370 megabecquerel (MBq) (10 millicurie \[mCi\]) of \[18F\]GTP1.

Drug: [18F]GTP1

Interventions

[18F]GTP1 DRUG

Participants will receive \[18F\]GTP1 as per the schedule specified in the arm description.

Also known as: [18F]G02941054, [18F]MNI-798, [18F]RO6880276

[18F]GTP1

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For All Participants:
• \- Availability of a study partner who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to accompany the participant and provide information at visits
• For Healthy Participants:
• Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the Baseline \[18F\]GTP1 imaging visit
• Have no cognitive complaint
• Have a Clinical Dementia Rating Scale (CDR) global score = 0
• Have a Mini-Mental State Examination (MMSE) score of 28-30
• For Participants With a Diagnosis of AD:
• Participants with mild or moderate AD must meet National Institute on Aging - Alzheimer's Association (NIA-AA) core clinical criteria for probable AD dementia, with an amnestic presentation
• Participants with prodromal AD must meet NIA-AA core clinical criteria for mild cognitive impairment (MCI)
• Have screening \[18F\]florbetapir PET imaging demonstrating amyloid binding based on qualitative visual read

You may not qualify if:

• Medications taken for symptomatic treatment of AD must remain stable for at least 30 days prior to screening visit
• Satisfy one of the following subgroups: Approximately 20 prodromal AD (MMSE 24-30, CDR = 0.5); Approximately 20 mild AD (MMSE 22-30, CDR = 0.5 or 1); Approximately 20 moderate AD (MMSE 16-21, CDR = 0.5 or 1 or 2)
• Current or prior history of any drug or alcohol abuse
• Participants with any significant psychiatric, neurological, or unstable medical disorder expected to interfere with the study
• Participants unable to undergo MRI and PET scan
• For participants contributing CSF samples, any contraindication to lumbar puncture
• Prior participation in other research protocols or clinical care in the last year such a radiation exposure combined with that from the present study exceeds an effective dose of 50 millisievert (mSV), the allowable annual limit for research participants as stipulated by the Food and Drug Administration (FDA)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (16)

Molecular NeuroImaging

New Haven, Connecticut, 06510, United States

Location

KI Health Partners, LLC; New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

Neuropsychiatric Research; Center of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

NeuroStudies.net, LLC

Decatur, Georgia, 30033, United States

Location

Acadia Clinical Research; Dr. Henderson's Office

Bangor, Maine, 04401, United States

Location

Donald S. Marks, M.D., P.C.; Medical Center

Plymouth, Massachusetts, 02360, United States

Location

Alzheimers Disease Center

Quincy, Massachusetts, 02169, United States

Location

NeuroCognitive Institute

Mount Arlington, New Jersey, 07856, United States

Location

Bio Behavioral Health

Toms River, New Jersey, 08755, United States

Location

Advanced Medical Research

Maumee, Ohio, 43537, United States

Location

Lehigh Center Clinical Research

Allentown, Pennsylvania, 18104, United States

Location

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, 02914, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Related Publications (3)

• Sanabria Bohorquez SM, Baker S, Manser PT, Tonietto M, Galli C, Wildsmith KR, Zou Y, Kerchner GA, Weimer R, Teng E. Evaluation of partial volume correction and analysis of longitudinal [18F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models. Front Neuroimaging. 2024 Mar 28;3:1355402. doi: 10.3389/fnimg.2024.1355402. eCollection 2024.

  PMID: 38606196 DERIVED

• Teng E, Manser PT, Sanabria Bohorquez S, Wildsmith KR, Pickthorn K, Baker SL, Ward M, Kerchner GA, Weimer RM. Baseline [18F]GTP1 tau PET imaging is associated with subsequent cognitive decline in Alzheimer's disease. Alzheimers Res Ther. 2021 Dec 1;13(1):196. doi: 10.1186/s13195-021-00937-x.

  PMID: 34852837 DERIVED

• Blennow K, Chen C, Cicognola C, Wildsmith KR, Manser PT, Bohorquez SMS, Zhang Z, Xie B, Peng J, Hansson O, Kvartsberg H, Portelius E, Zetterberg H, Lashley T, Brinkmalm G, Kerchner GA, Weimer RM, Ye K, Hoglund K. Cerebrospinal fluid tau fragment correlates with tau PET: a candidate biomarker for tangle pathology. Brain. 2020 Feb 1;143(2):650-660. doi: 10.1093/brain/awz346.

  PMID: 31834365 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

(18F)GTP1

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 28, 2015
• Study Start: December 23, 2015
• Primary Completion: June 11, 2019
• Study Completion: June 11, 2019
• Last Updated: December 23, 2019

Record last verified: 2019-12

Locations

US (16)