Tau Screening Study in Patients With Early Symptomatic AD

A Multicenter Screening Study With Flortaucipir F 18 in Patients With Early Symptomatic AD

This protocol is designed to serve as a pre-screening study for subjects who are potentially eligible for Alzheimer's Disease (AD) therapeutic trials that require tau imaging for inclusion by means of a flortaucipir F18 Positron Emission Tomography (PET) scan.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Procedure: Brain PET Scan; Drug: Flortaucipir F18

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
• United States
  • California
    • San Diego, California, United States, 92103
      • Pacific Research Network
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Orlando, Florida, United States, 32806
      • Bioclinica (Compass Research)
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research
  • Pennsylvania
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women between the ages of 60 and 85 years of age at the time of consent
• Patients with gradual and progressive change in memory function for a period equal to or greater than six months
• Patients who have a Mini Mental State Examination (MMSE) score in the 20-27 range
• Patients who are willing to undergo a PET scan using flortaucipir F 18
• Patients who give informed consent or have a legally authorized representative (LAR) to consent for enrollment

Exclusion Criteria:

• Patients who lack adequate premorbid literacy, vision, or hearing to complete the required psychometric testing in the investigator's opinion
• Females of childbearing potential who are not surgically sterile, not refraining from sexual activity, or not using reliable contraception methods. Females of childbearing potential must not be pregnant (negative serum β-Human Chorionic Gonadotropin [HCG] at screening and negative urine β-HCG prior to flortaucipir F 18 injection) or breastfeeding at screening. Females should agree to avoid becoming pregnant by refraining from sexual activity or using reliable contraceptive methods for 24 hours following flortaucipir F 18 injection administration.
• Have significant neurological disease affecting the Central Nervous System (CNS) (other than AD) that may affect cognition or ability to complete the study, including but not limited to, other types of dementia, serious brain infections, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures (except febrile childhood seizures).
• Patients with any current primary psychiatric diagnosis other than AD if, in the opinion of the investigator, the disorder/symptom is likely to confound interpretation of drug effect, affect cognitive assessment, or affect the patient's ability to complete the study (patients with history of schizophrenia or other chronic psychosis are excluded).
• Intend to use drugs known to significantly prolong the QT interval within 14 days or 5 half-lives (whichever is longer) of a scheduled screening/baseline flortaucipir F 18 PET scan, or have medical history of risk factors for Torsades du Pointes.
• Have an average electrocardiography (ECG) corrected QT (QTcF) interval measurement > 450 msec (men) or > 470 msec (women) at screening (as determined at the investigational site).
• Have ocular pathology that significantly limits ability to reliably evaluate vision or the retina.
• Have a history of alcohol or drug disorder (except tobacco use disorder) within 2 years before the screening visit
• Have a current serious or unstable illness including retinal, cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study; or has a life expectancy of less than 24 months.
• Has a history of cancer within the last five years, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-progressive prostate cancer, or other cancers with low risk of recurrence or spread
• Patients with a past history (suspected or confirmed) of Hepatitis B or Hepatitis C
• History of vitiligo and/or current evidence of post-inflammatory hypopigmentation
• Have had prior treatment with a passive anti-amyloid immunotherapy less than five half-lives prior to randomization.
• Have previously participated in any other study investigating active immunization against amyloid beta (Aβ)
• Patients that are currently enrolled in any other interventional clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
• Contraindication to PET
• Has hypersensitivity to flortaucipir F 18 or any of its excipients
• Present or planned exposure to ionizing radiation that, in combination with the planned administration of study PET ligands, would result in a cumulative exposure that exceeds local recommended exposure limits
• Has previous magnetic resonance imaging (MRI) evidence of significant abnormality that would suggest another potential etiology for progressive dementia or a clinically significant finding that may impact patient's potential to safely participate in study
• Have contraindications for MRI, including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker
• Have poor venous access
• Are investigator site personnel directly affiliated with this study and/or immediate families; immediate family is defined as a spouse, parent, child, or sibling (biological or legally adopted)
• Are Lilly employees or are employees of third-party organizations (TPOs) involved in a study that requires exclusion of their employees
• Are otherwise unsuitable for a study of this type in the opinion of the investigator
• Have received treatment with a stable dose of an acetylcholinesterase inhibitor (AChEI) and/or memantine for less than two months before randomization (if a patient has recently stopped an AChEI and/or memantine, he/she must have discontinued treatment at least two months before randomization).
• Current use of strong inducers of CYP3A
• Are currently on medication(s) known to significantly prolong the QT interval
• Have allergies to either monoclonal antibodies, diphenhydramine, epinephrine, or methylprednisolone
• Have known allergies to LY3002813, related compounds, or any components of the formulation; or history of significant atopy
• Have known allergies to LY3202626, related compounds, or any components of the formulation
• Changes in concomitant medications that could potentially affect cognition and their dosing should be stable for at least one month before screening, and between screening and randomization (does not apply to medications discontinued due to exclusions or with limited duration of use, such as antibiotics)

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: Flortaucipir PET Scan	Procedure: Brain PET Scan; positron emission tomography (PET) scan of the brain; Drug: Flortaucipir F18; 370 megabecquerel (MBq) IV single-dose; Other Names: 18F-AV-1451; [F-18]T807

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flortaucipir Qualitative Results (Visual Reads)	Flortaucipir PET scans were rated visually by an expert reader as follows: Not consistent with an AD pattern (τAD-), Moderate AD pattern (τAD+), or Advanced AD pattern and likely to progress (τAD++). Eligibility for AACG study was determined from the flortaucipir PET scan quantitation (SUVr; see below) according to protocol-specified criteria that excluded subjects with tau PET signal that was above or below study criteria.	baseline scan
Flortaucipir Quantitative Results (SUVr)	Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. Visual read categories as described for previous measure. Eligibility for AACG study was determined from the flortaucipir PET scan quantitation (SUVr; see below) according to protocol-specified criteria that excluded subjects with tau PET signal that was above or below study criteria.	baseline scan

Collaborators and Investigators

• Sponsor: Avid Radiopharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): August 31, 2018

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 26, 2017

Study Record Updates

• Last Update Posted (Actual): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

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: 18F-AV-1451-A23

Drug and device information, study documents

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