A Study of Flortaucipir PET in Healthy Volunteers and Cognitively Impaired Subjects

• Sponsor: Avid Radiopharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01992380
• Collaborator: (none)
• Enrollment: 24
• Locations: 2
• Arms: 3
• Actual Duration (Months): 6.5
• Patients Per Site: 12
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This study will test if two flortaucipir PET scans up to 4 weeks apart in healthy volunteers, MCI and AD subjects provide the same results.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Flortaucipir F18; Procedure: Brain PET scan	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Test-Retest Reproducibility of 18F-AV-1451 Injection for Brain Imaging of Tau in Healthy Volunteers and Cognitively Impaired Subjects.
• Actual Study Start Date: Nov 13, 2013
• Actual Primary Completion Date: May 30, 2014
• Actual Study Completion Date: May 30, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy Volunteer Subjects Healthy males or females 50 years or older with no evidence of cognitive impairment	Drug: Flortaucipir F18; IV injection, 370 MBq (10 mCi), two doses up to four weeks apart; Other Names: [F18]T807 18F-AV-1451 Tauvid ; Procedure: Brain PET scan; positron emission tomography (PET) scan of the brain at 80-100 and 110-130 minutes after injection
Experimental: MCI subjects Subjects 50 years or older with mild cognitive impairment (MCI)	Drug: Flortaucipir F18; IV injection, 370 MBq (10 mCi), two doses up to four weeks apart; Other Names: [F18]T807 18F-AV-1451 Tauvid ; Procedure: Brain PET scan; positron emission tomography (PET) scan of the brain at 80-100 and 110-130 minutes after injection
Experimental: Probable AD Subjects Subjects 50 years or older with probable Alzheimer's Disease (AD)	Drug: Flortaucipir F18; IV injection, 370 MBq (10 mCi), two doses up to four weeks apart; Other Names: [F18]T807 18F-AV-1451 Tauvid ; Procedure: Brain PET scan; positron emission tomography (PET) scan of the brain at 80-100 and 110-130 minutes after injection

Outcome Measures

Primary Outcome Measures

1. Test-Retest Reproducibility [80-100 minutes postdose]

   Evaluate test-retest reproducibility of flortaucipir for brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVRs) for each scan, normalized to the cerebellar crus. A combination volume of interest (VOI) = weighted average of parietal, temporal, and occipital regions was used. The protocol pre-specified that test-retest endpoint was to be calculated for the combined group of healthy volunteers and cognitively impaired subjects

2. Test-Retest Reproducibility [110-130 minutes postdose]

   Evaluate test-retest reproducibility of 18F-AV-1451 for brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVRs) for each scan, normalized to the cerebellar crus. A combination volume of interest (VOI) = weighted average of parietal, temporal, and occipital regions was used. The protocol pre-specified that test-retest endpoint was to be calculated for the combined group of healthy volunteers and cognitively impaired subjects

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy Volunteers

• Male or female subjects ≥ 50 years of age

• Mini-mental state examination (MMSE) ≥ 29

• MCI Subjects

• Male or female subjects ≥ 50 years of age

• MMSE ≥ 24

• Have MCI consistent with National Institute on Aging-Alzheimer's Association (NIA-AA) working group's diagnostic guidelines for AD

• Have a study partner that can report on subject's activities of daily living

• Probable AD Subjects

• Male or female subjects ≥ 50 years of age

• MMSE > 10

• Meet clinical criteria for probable AD based on the NIA-AA working group's diagnostic guidelines for AD

• Have a study partner that can report on subject's activities of daily living

Exclusion Criteria:

• Current clinically significant psychiatric disease

• Evidence of structural brain abnormalities

• Evidence of dementing illness other than AD

• Current clinically significant cardiovascular disease or ECG abnormalities, or additional risk factors for Torsades de Pointes

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

• History of alcohol or substance abuse or dependence

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

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Newport Beach	California	United States	92663
2	Research Site	New Haven	Connecticut	United States	06510

Sponsors and Collaborators

• Avid Radiopharmaceuticals

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Avid Radiopharmaceuticals
• ClinicalTrials.gov Identifier: NCT01992380
• Other Study ID Numbers: 18F-AV-1451-A03
• First Posted: Nov 25, 2013
• Last Update Posted: Sep 7, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Recruitment Details	Enrollment between Nov 2013 and May 2014

Arm/Group Title	Healthy Volunteer Subjects	MCI Subjects	Probable AD Subjects
Arm/Group Description	Healthy males or females 50 years or older with no evidence of cognitive impairment Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain	Subjects 50 years or older with mild cognitive impairment (MCI) Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain	Subjects 50 years or older with probable Alzheimer's Disease (AD) Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain
Period Title: Overall Study
STARTED	6	8	10
COMPLETED	6	8	10
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Healthy Volunteer Subjects	MCI Subjects	Probable AD Subjects	Total
Arm/Group Description	Healthy males or females 50 years or older with no evidence of cognitive impairment Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain	Subjects 50 years or older with mild cognitive impairment (MCI) Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain	Subjects 50 years or older with probable Alzheimer's Disease (AD) Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain	Total of all reporting groups
Overall Participants	6	8	10	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.8 (9.5)	70.3 (5.4)	74.4 (7.3)	70.1 (8.4)
Sex: Female, Male (Count of Participants)
Female	4 66.7%	2 25%	2 20%	8 33.3%
Male	2 33.3%	6 75%	8 80%	16 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	8 100%	10 100%	24 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 16.7%	0 0%	0 0%	1 4.2%
White	5 83.3%	8 100%	10 100%	23 95.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%	8 100%	10 100%	24 100%
Mini Mental Status Exam (MMSE) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	29.7 (0.52)	28.3 (1.58)	23.9 (4.58)	26.8 (3.95)

Outcome Measures

1. Primary Outcome

Title	Test-Retest Reproducibility
Description	Evaluate test-retest reproducibility of flortaucipir for brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVRs) for each scan, normalized to the cerebellar crus. A combination volume of interest (VOI) = weighted average of parietal, temporal, and occipital regions was used. The protocol pre-specified that test-retest endpoint was to be calculated for the combined group of healthy volunteers and cognitively impaired subjects
Time Frame	80-100 minutes postdose

Outcome Measure Data

Analysis Population Description

All subjects with a valid test and re-test scan. The 80-100 minute scan was not done for one subject in the healthy volunteer group due to technical difficulties with the scanning apparatus

Arm/Group Title	All Subjects
Arm/Group Description	All study subjects Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain
Measure Participants	24
Test Imaging	1.342 (0.341)
Retest Imaging	1.355 (0.309)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Subjects
	Comments	Intraclass correlation coefficient [ICC(2,1)] analysis from Shrout and Fleiss
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ICC
	Estimated Value	0.971
	Confidence Interval	(2-Sided) 95%; 0.935 to 0.988
	Parameter Dispersion	Type: Value:
	Estimation Comments	Assessed the agreement between the test and retest imaging of the combination VOI SUVr

2. Primary Outcome

Title	Test-Retest Reproducibility
Description	Evaluate test-retest reproducibility of 18F-AV-1451 for brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVRs) for each scan, normalized to the cerebellar crus. A combination volume of interest (VOI) = weighted average of parietal, temporal, and occipital regions was used. The protocol pre-specified that test-retest endpoint was to be calculated for the combined group of healthy volunteers and cognitively impaired subjects
Time Frame	110-130 minutes postdose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	All study subjects Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain
Measure Participants	24
Test Imaging	1.459 (0.455)
Retest Imaging	1.457 (0.396)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Subjects
	Comments	Intraclass correlation coefficient [ICC(2,1)] analysis from Shrout and Fleiss
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ICC
	Estimated Value	0.968
	Confidence Interval	(2-Sided) 95%; 0.926 to 0.986
	Parameter Dispersion	Type: Value:
	Estimation Comments	Assessed the agreement between the test and retest imaging of the combination VOI SUVr

Adverse Events

Time Frame	End of study for AE reporting was 48 hours after flortaucipir administration at each imaging visit.
Adverse Event Reporting Description	Adverse Events were defined as occurring or worsening after injection of dose, within 48 hours post injection, at an imaging visit. AEs occurring after study drug administration, but outside that window were not recorded, unless considered attributable to flortaucipir.
Arm/Group Title	Healthy Volunteer Subjects		MCI Subjects		Probable AD Subjects
Arm/Group Description	Healthy males or females 50 years or older with no evidence of cognitive impairment Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain		Subjects 50 years or older with mild cognitive impairment (MCI) Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain		Subjects 50 years or older with probable Alzheimer's Disease (AD) Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart Brain PET scan: positron emission tomography (PET) scan of the brain
All Cause Mortality
	Healthy Volunteer Subjects		MCI Subjects		Probable AD Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/8 (0%)		0/10 (0%)
Serious Adverse Events
	Healthy Volunteer Subjects		MCI Subjects		Probable AD Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/8 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Volunteer Subjects		MCI Subjects		Probable AD Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/8 (0%)		3/10 (30%)
Gastrointestinal disorders
diarrhoea	0/6 (0%)	0	0/8 (0%)	0	1/10 (10%)	1
Nervous system disorders
dysgeusia	1/6 (16.7%)	1	0/8 (0%)	0	0/10 (0%)	0
Vascular disorders
hypertension	0/6 (0%)	0	0/8 (0%)	0	2/10 (20%)	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.