Clinical trial NCT03322462: Tau Screening Study in Patients With Early Symptomatic AD
Official title: A Multicenter Screening Study With Flortaucipir F 18 in Patients With Early Symptomatic AD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease
Lead sponsor: Avid Radiopharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-10-26
Enrollment: 155
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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)

Primary outcomes:
measure: Flortaucipir Qualitative Results (Visual Reads)
timeFrame: baseline scan
measure: Flortaucipir Quantitative Results (SUVr)
timeFrame: baseline scan
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Pacific Research Network
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Orlando
country: United States
facility: Bioclinica (Compass Research)
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research
state: Florida
city: Newton
country: United States
facility: Boston Center for Memory
state: Massachusetts
city: Winston-Salem
country: United States
facility: PMG Research
state: North Carolina
city: Willow Grove
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Bennington
country: United States
facility: The Memory Clinic
state: Vermont
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
Study officials:
affiliation: Avid Radiopharmaceuticals, Inc.
name: Chief Medical Officer
role: STUDY_CHAIR
References: