Tau Screening Study in Patients With Early Symptomatic AD
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Intervention: Flortaucipir F18; Brain PET Scan
Intervention description: 370 megabecquerel (MBq) IV single-dose; positron emission tomography (PET) scan of the brain
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 155.0
Sex: All
Minimum age: 60 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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)