Tau Screening Study in Patients With Early Symptomatic AD

• Sponsor: Avid Radiopharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03322462
• Collaborator: (none)
• Enrollment: 155
• Locations: 10
• Arm: 1
• Actual Duration (Months): 9.3
• Patients Per Site: 15.5
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Flortaucipir F18; Procedure: Brain PET Scan	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Multicenter Screening Study With Flortaucipir F 18 in Patients With Early Symptomatic AD
• Actual Study Start Date: Nov 21, 2017
• Actual Primary Completion Date: Aug 31, 2018
• Actual Study Completion Date: Aug 31, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Flortaucipir Qualitative Results (Visual Reads) [baseline scan]

   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.

2. Flortaucipir Quantitative Results (SUVr) [baseline scan]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Research Network	San Diego	California	United States	92103
2	Syrentis Clinical Research	Santa Ana	California	United States	92705
3	Brain Matters Research	Delray Beach	Florida	United States	33445
4	Bioclinica (Compass Research)	Orlando	Florida	United States	32806
5	Axiom Clinical Research	Tampa	Florida	United States	33609
6	Boston Center for Memory	Newton	Massachusetts	United States	02459
7	PMG Research	Winston-Salem	North Carolina	United States	27103
8	Abington Neurological Associates	Willow Grove	Pennsylvania	United States	19090
9	The Memory Clinic	Bennington	Vermont	United States	05201
10	Toronto Memory Program	Toronto	Ontario	Canada	M3B 2S7

Sponsors and Collaborators

• Avid Radiopharmaceuticals

Investigators

• Study Chair: Chief Medical Officer, Avid Radiopharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Sep 11, 2017
• Statistical Analysis Plan - Nov 26, 2018

More Information

Publications

None provided.

• Responsible Party: Avid Radiopharmaceuticals
• ClinicalTrials.gov Identifier: NCT03322462
• Other Study ID Numbers: 18F-AV-1451-A23
• First Posted: Oct 26, 2017
• Last Update Posted: Aug 24, 2020
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Recruitment Details	Enrollment occurred between Nov 2017 and Aug 2018. Recruited subjects with clinically diagnosed early AD who were interested in participating in AD therapeutic clinical trial AACG (Eli Lilly and Company; TRAILBLAZER-ALZ; NCT03367403)

Arm/Group Title	Early Symptomatic AD Subjects
Arm/Group Description	Early Symptomatic AD subjects in the flortaucipir PET scan arm
Period Title: Overall Study
STARTED	155
Flortaucipir PET Scan	155
COMPLETED	152
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Early Symptomatic AD Subjects
Arm/Group Description	Early Symptomatic AD subjects in the flortaucipir PET scan arm
Overall Participants	155
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.7 (6.19)
Sex: Female, Male (Count of Participants)
Female	76 49%
Male	79 51%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 1.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	15 9.7%
White	137 88.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
MMSE (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	24.5 (2.18)

Outcome Measures

1. Primary Outcome

Title	Flortaucipir Qualitative Results (Visual Reads)
Description	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.
Time Frame	baseline scan

Outcome Measure Data

Analysis Population Description

Includes all subjects who completed the study with valid flortaucipir PET scan (n=152)

Arm/Group Title	Early Symptomatic AD, Eligible for AACG Study	Early Symptomatic AD, Ineligible for AACG Study	Early Symptomatic AD (Total)
Arm/Group Description	Subjects determined to be eligible for the AACG Study from the flortaucipir PET scan arm.	Subjects who were not eligible for the AACG Study from the flortaucipir PET scan arm.	All subjects with early symptomatic AD from the flortaucipir PET scan arm
Measure Participants	58	94	152
τAD++, advanced AD pattern	56 36.1%	22 NaN	78 NaN
τAD+, moderate AD pattern	2 1.3%	8 NaN	10 NaN
τAD-, pattern not consistent with AD	0 0%	64 NaN	64 NaN

2. Primary Outcome

Title	Flortaucipir Quantitative Results (SUVr)
Description	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.
Time Frame	baseline scan

Outcome Measure Data

Analysis Population Description

SUVr was not collected for patients with a τAD- result

Arm/Group Title	Early Symptomatic AD, Eligible for AACG Study	Early Symptomatic AD, Ineligible for AACG Study	Early Symptomatic AD (Total)
Arm/Group Description	Subjects determined to be eligible for the AACG Study from the flortaucipir PET scan arm.	Subjects who were not eligible for the AACG Study from the flortaucipir PET scan arm.	All subjects with early symptomatic AD from the flortaucipir PET scan arm
Measure Participants	58	30	88
SUVr all	1.21207 (0.119729)	1.48576 (0.316435)	1.30537 (0.244527)
SUVr τAD++ subjects	1.21518 (0.120696)	1.65880 (0.143067)	1.34031 (0.237395)
SUVr τAD+ subjects	1.12490 (0.012021)	1.00991 (0.023239)	1.03291 (0.052789)

Adverse Events

Time Frame	48 hours after study drug administration
Adverse Event Reporting Description	Adverse events (AEs) were collected at scan visits, regardless of attribution to study drug. End of study for AE reporting was 48 hours after the last study drug administration. AEs occurring after study drug administration, but outside that window were not recorded, unless considered attributable to study drug.
Arm/Group Title	Safety Analysis Population
Arm/Group Description	All subjects with early symptomatic AD from the flortaucipir PET scan arm who received one dose of flortaucipir
All Cause Mortality
	Safety Analysis Population
	Affected / at Risk (%)	# Events
Total	0/155 (0%)
Serious Adverse Events
	Safety Analysis Population
	Affected / at Risk (%)	# Events
Total	0/155 (0%)
Other (Not Including Serious) Adverse Events
	Safety Analysis Population
	Affected / at Risk (%)	# Events
Total	2/155 (1.3%)
Gastrointestinal disorders
diarrhoea	2/155 (1.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.