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

• ClinicalTrials.gov Identifier: NCT02640092
• Recruitment Status: Completed
• First Posted: December 28, 2015
• Last Update Posted: December 23, 2019
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: [18F]GTP1	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Longitudinal Evaluation of [18F]GTP1 as a PET Radioligand for Imaging Tau in the Brain of Patients With Prodromal, Mild, and Moderate Alzheimer's Disease Compared to Healthy Volunteers
• Actual Study Start Date: December 23, 2015
• Actual Primary Completion Date: June 11, 2019
• Actual Study Completion Date: June 11, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: [18F]GTP1; 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; Participants will receive [18F]GTP1 as per the schedule specified in the arm description.; Other Names: [18F]G02941054; [18F]MNI-798; [18F]RO6880276

Outcome Measures

Primary Outcome Measures :

1. Change in Standardized Uptake Value Ratio (SUVR) as Measured by [18F]GTP1 [ Time Frame: From Baseline to 18 months ]

Secondary Outcome Measures :

1. Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)13 [ Time Frame: From Baseline to 18 months ]
2. Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Volumetric Magnetic Resonance Imaging (MRI) Measures [ Time Frame: From Baseline to 18 months ]
3. Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Cerebrospinal Fluid (CSF) Markers [ Time Frame: From Baseline to 18 months ]
4. Percentage of Participants With Adverse Events (AEs) [ Time Frame: From Baseline to 18 months ]
5. Test-Retest Variability Based on [18F]GTP1 PET Scans [ Time Frame: From date of test scan to 7-21 days after test scan ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

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
• A brain MRI consistent with a diagnosis of AD, with no evidence of non-AD disease to account for dementia or MRI exclusion criteria
• 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)

Exclusion Criteria:

• 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)

Contacts and Locations

Locations

United States, Connecticut

Molecular NeuroImaging

New Haven, Connecticut, United States, 06510

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

Stamford, Connecticut, United States, 06905

United States, Florida

Neuropsychiatric Research; Center of Southwest Florida

Fort Myers, Florida, United States, 33912

Miami Jewish Health Systems

Miami, Florida, United States, 33137

Bioclinica Research

Orlando, Florida, United States, 32806

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30303

NeuroStudies.net, LLC

Decatur, Georgia, United States, 30033

United States, Maine

Acadia Clinical Research; Dr. Henderson's Office

Bangor, Maine, United States, 04401

United States, Massachusetts

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

Plymouth, Massachusetts, United States, 02360

Alzheimers Disease Center

Quincy, Massachusetts, United States, 02169

United States, New Jersey

NeuroCognitive Institute

Mount Arlington, New Jersey, United States, 07856

Bio Behavioral Health

Toms River, New Jersey, United States, 08755

United States, Ohio

Advanced Medical Research

Maumee, Ohio, United States, 43537

United States, Pennsylvania

Lehigh Center Clinical Research

Allentown, Pennsylvania, United States, 18104

United States, Rhode Island

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, United States, 02914

Butler Hospital

Providence, Rhode Island, United States, 02906

Sponsors and Collaborators

Genentech, Inc.

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Höglund 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.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT02640092
• Other Study ID Numbers: GN30009; G0097 ( Other Identifier: InVicro )
• First Posted: December 28, 2015
• Last Update Posted: December 23, 2019
• Last Verified: December 2019

Additional relevant MeSH terms:

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