Follow up 18F-AV-1451 Scan in Confirmatory Cohort Subjects From Study 18F-AV-1451-A05

• Sponsor: Avid Radiopharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02795780
• Collaborator: (none)
• Enrollment: 79
• Locations: 22
• Arm: 1
• Duration (Months): 12.9
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate longitudinal change of tau deposition as measured by flortaucipir F 18 uptake over time.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: An Open Label, Multicenter Study Evaluating the Imaging Characteristics of a Follow up 18F-AV-1451 Scan in Subjects That Participated in the Confirmatory Cohort of 18F-AV-1451-A05
• Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Aug 28, 2017
• Actual Study Completion Date: Aug 28, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Tau Deposition Over Time by Diagnostic Group and Amyloid Status [18 months]

   Change in flortaucipir standardized uptake value ratio (SUVr) over 18 months. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. A positive change in SUVr represents an increase in tau deposition in the brain. Change = 18 month SUVr - baseline SUVr obtained in Study A05.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmatory cohort subjects who completed the 18F-AV-1451-A05 (NCT02016560) study

Exclusion Criteria:

• Current clinically significant cardiovascular disease, ECG abnormalities, risk factors for Torsades de Pointes (TdP), or are taking drugs known to cause QT prolongation

• Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer

• Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception

• Have had a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session

• Have received or participated in a trial with investigational medications in the past 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Alzheimer's Institute	Phoenix	Arizona	United States	85006
2	Imaging Endpoints	Scottsdale	Arizona	United States	85258
3	Mayo Clinic Arizona	Scottsdale	Arizona	United States	85259
4	Banner Sun Health Research Institute	Sun City	Arizona	United States	85351
5	Institute for Brain Aging and Dementia, UC Irvine	Irvine	California	United States	92697
6	21st Century Oncology	Newport Beach	California	United States	92663
7	Alzheimer's Disease Center, UC Davis	Sacramento	California	United States	95817
8	California Medical Clinic for Headache	Santa Monica	California	United States	90404
9	Neuropsychiatric Research Center of Southwest Florida	Fort Myers	Florida	United States	33912
10	Compass Research, LLC	Orlando	Florida	United States	32806
11	Meridien Research	Saint Petersburg	Florida	United States	33709
12	University of South Florida Health Byrd Alzheimer's Institute	Tampa	Florida	United States	33613
13	Premiere Research Institute	West Palm Beach	Florida	United States	33407
14	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
15	Boston University School of Medicine	Boston	Massachusetts	United States	02118
16	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
17	Las Vegas Radiology	Las Vegas	Nevada	United States	89113
18	New York University Center for Brain Health	New York	New York	United States	10016
19	Duke University Medical Center	Durham	North Carolina	United States	27710
20	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
21	Rhode Island Hospital	Providence	Rhode Island	United States	02903
22	Butler Hospital	Providence	Rhode Island	United States	02906

Sponsors and Collaborators

• Avid Radiopharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 22, 2016
• Statistical Analysis Plan - Jan 11, 2018

More Information

Publications

None provided.

• Responsible Party: Avid Radiopharmaceuticals
• ClinicalTrials.gov Identifier: NCT02795780
• Other Study ID Numbers: 18F-AV-1451-A18
• First Posted: Jun 10, 2016
• Last Update Posted: Aug 24, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Recruitment Details	Enrolled between Aug 2016 and Aug 2017. The only subjects eligible were those who completed the Confirmatory Phase of Study A05 (NCT02016560).

Arm/Group Title	AD Subjects	MCI Subjects
Arm/Group Description	Clinically diagnosed dementia with a suspected neurodegenerative cause with an MMSE score ≥20 and ≤27	Clinically diagnosed mild cognitive impairment with a suspected neurodegenerative cause with an MMSE score ≥20 and ≤27
Period Title: Overall Study
STARTED	25	54
COMPLETED	25	54
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	AD Subjects	MCI Subjects	Total
Arm/Group Description	Clinically diagnosed dementia with a suspected neurodegenerative cause with an MMSE score ≥20 and ≤27 from the flortaucipir PET scan arm	Clinically diagnosed mild cognitive impairment with a suspected neurodegenerative cause with an MMSE score ≥20 and ≤27 from the flortaucipir PET scan arm	Total of all reporting groups
Overall Participants	25	54	79
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.8 (10.63)	73.2 (9.1)	73.4 (9.54)
Sex: Female, Male (Count of Participants)
Female	9 36%	22 40.7%	31 39.2%
Male	16 64%	32 59.3%	48 60.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4%	3 5.6%	4 5.1%
Not Hispanic or Latino	24 96%	51 94.4%	75 94.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	3 5.6%	3 3.8%
White	25 100%	51 94.4%	76 96.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%	54 100%	79 100%
MMSE (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	23.7 (2.39)	25.9 (1.48)	25.2 (2.06)
CDR-SB (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.8 (1.53)	2.6 (1.91)	3.3 (2.05)
Amyloid status (Count of Participants)
Amyloid positive	19 76%	26 48.1%	45 57%
Amyloid Negative	6 24%	28 51.9%	34 43%

Outcome Measures

1. Primary Outcome

Title	Change in Tau Deposition Over Time by Diagnostic Group and Amyloid Status
Description	Change in flortaucipir standardized uptake value ratio (SUVr) over 18 months. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. A positive change in SUVr represents an increase in tau deposition in the brain. Change = 18 month SUVr - baseline SUVr obtained in Study A05.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Excluded 1 MCI Aβ+ and 1 MCI Aβ- subject for whom 18 month follow-up clinical was not available

Arm/Group Title	AD Aβ+ Subjects	AD Aβ- Subjects	MCI Aβ+ Subjects	MCI Aβ- Subjects
Arm/Group Description	Amyloid positive AD subjects from the flortaucipir PET scan arm	Amyloid negative AD subjects from the flortaucipir PET scan arm	Amyloid positive MCI subjects from the flortaucipir PET scan arm	Amyloid negative MCI subjects from the flortaucipir PET scan arm
Measure Participants	19	6	26	26
Least Squares Mean (Standard Deviation) [standardized uptake value ratio (SUVr)]	0.0205 (0.01871)	-0.0912 (0.03619)	0.0352 (0.01185)	-0.0124 (0.01185)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AD Aβ+ Subjects, AD Aβ- Subjects
	Comments	Test of whether difference in least squares mean change is 0
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0166
	Comments	No adjustments for multiplicity. No a priori threshold defined.
	Method	ANCOVA
	Comments	Adjusted for baseline SUVr, age, and diagnosis group (AD/MCI)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MCI Aβ+ Subjects, MCI Aβ- Subjects
	Comments	Test of whether difference in least squares mean change is 0
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0108
	Comments	No adjustments for multiplicity. No a priori threshold defined.
	Method	ANCOVA
	Comments	Adjusted for baseline SUVr, age, and diagnosis group (AD/MCI)

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. AEs occurring after study drug administration, but outside that window were not recorded, unless considered attributable to study drug.
Arm/Group Title	MCI Subjects		AD Subjects
Arm/Group Description	MCI subjects receiving a dose of flortaucipir		AD subjects receiving a dose of flortaucipir
All Cause Mortality
	MCI Subjects		AD Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/25 (0%)
Serious Adverse Events
	MCI Subjects		AD Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	MCI Subjects		AD Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/54 (3.7%)		0/25 (0%)
General disorders
injection site pain	1/54 (1.9%)	1	0/25 (0%)	0
Nervous system disorders
dizziness	1/54 (1.9%)	1	0/25 (0%)	0
Vascular disorders
flushing	1/54 (1.9%)	1	0/25 (0%)	0

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.