Trial Outcomes & Findings for Evaluation of Flortaucipir PET Signal and Cognitive Change in Early Alzheimer's Disease (NCT NCT03901105)

Last Updated: 2020-08-28

Results Overview

Baseline flortaucipir F 18 PET imaging results were determined by majority read (see Baseline Characteristics for description). Clinically meaningful deterioration (CMD) was defined for the primary endpoint as a worsening of the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score of one point or more. The clinical dementia rating (CDR) examines 6 categories of cognitive functioning domains. Each domain is scored on a scale ranging from 0 to 3 (including 0.5). A CDR-SB was generated as the sum of the values in each of the 6 domains. The CDR-SB sum scores range from 0 to 18, with higher scores indicating greater cognitive impairment and a 1 point worsening is considered a clinically significant symptom change.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

205 participants

Primary outcome timeframe

Within 18 months of scan

Results posted on

2020-08-28

Participant Flow

Scans were acquired from subjects previously enrolled in the AZES (NCT02245737) PET substudy (N=205), including mild AD (n=141) and mild cognitive impairment (MCI) due to AD (n=64).

To be included in the study, subjects had to have a valid baseline flortaucipir PET scan and clinical dementia rating (CDR) assessments at baseline and 18 months.

Participant milestones

Participant milestones
Measure	All Subjects Mild AD and MCI due to AD from the flortaucipir PET scan arm
Overall Study STARTED	205
Overall Study COMPLETED	205
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of Flortaucipir PET Signal and Cognitive Change in Early Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Scans n=205 Participants Mild AD and MCI due to AD from the flortaucipir PET scan arm
Age, Continuous	71.0 years STANDARD_DEVIATION 7.74 • n=93 Participants
Sex: Female, Male Female	100 Participants n=93 Participants
Sex: Female, Male Male	105 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	27 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	5 Participants n=93 Participants
Race (NIH/OMB) White	172 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Flortaucipir PET Scan Result tAD++	162 Participants n=93 Participants
Flortaucipir PET Scan Result tAD+	15 Participants n=93 Participants
Flortaucipir PET Scan Result tAD-	28 Participants n=93 Participants
Mean CDR-SB	3.69 units on a scale STANDARD_DEVIATION 1.475 • n=93 Participants

PRIMARY outcome

Timeframe: Within 18 months of scan

Outcome measures

Outcome measures
Measure	CMD (CDR-SB Change >=1) n=143 Participants Subjects who experienced at least a 1 point worsening in CDR-SB score over 18 months	No CMD n=62 Participants Subjects who experienced less than a 1 point worsening in CDR-SB score over 18 months
Risk Ratio for AD Symptom Progression on CDR-SB tAD++	119 Participants	43 Participants
Risk Ratio for AD Symptom Progression on CDR-SB tAD+	10 Participants	5 Participants
Risk Ratio for AD Symptom Progression on CDR-SB tAD-	14 Participants	14 Participants

SECONDARY outcome

Timeframe: Within 18 months of scan

Population: All subjects were eligible for this analysis; however, row totals reflect subjects for whom clinical measure data was available at baseline and 18 months.

Baseline flortaucipir F 18 PET imaging results were determined by majority read (see Baseline Characteristics for description). Clinically meaningful deterioration (CMD) was defined for the cognitive endpoints as follows: mini-mental status exam (MMSE) worsening of 3 points or greater, Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) worsening of 4 points or greater, Pfeffer's Functional Activities Questionnaire (FAQ) worsening of 3 points or greater, CDR global worsening of greater than 0 points. MMSE scores range from 0 to 30 with lower scores indicating worsening cognitive function. ADAS-Cog11 scores range from 0 to 70 with higher scores indicating worsening cognitive function. FAQ scores range from 0 to 30 with higher scores indicating worsening cognitive function. CDR global is scored on a 5 point scale (0, 0.5, 1, 2, 3) with higher scores indicating worsening cognitive function.

Outcome measures

Outcome measures
Measure	CMD (CDR-SB Change >=1) n=205 Participants Subjects who experienced at least a 1 point worsening in CDR-SB score over 18 months	No CMD n=205 Participants Subjects who experienced less than a 1 point worsening in CDR-SB score over 18 months
Risk Ratio for AD Symptom Progression on Various Clinical Measures MMSE · tAD++	112 Participants	49 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures MMSE · tAD+	6 Participants	8 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures MMSE · tAD-	15 Participants	13 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures ADAS-Cog · tAD++	98 Participants	59 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures ADAS-Cog · tAD+	6 Participants	8 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures ADAS-Cog · tAD-	8 Participants	20 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures FAQ · tAD++	111 Participants	47 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures FAQ · tAD+	9 Participants	5 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures FAQ · tAD-	14 Participants	14 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures CDR Global · tAD++	71 Participants	91 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures CDR Global · tAD+	7 Participants	8 Participants
Risk Ratio for AD Symptom Progression on Various Clinical Measures CDR Global · tAD-	9 Participants	19 Participants

SECONDARY outcome

Timeframe: baseline and 18 months

Population: All subjects were eligible for this analysis; however, row totals reflect subjects for whom clinical measure data was available at baseline and 18 months.

Mean change in cognitive/functional measures baseline between τAD++ and non-τAD++ (determined by baseline tau status), calculated by Mixed Model Repeat Measures (MMRM). CDR-SB scores range from 0 to 18, with higher scores indicating worsening cognitive impairment. MMSE scores range from 0 to 30 with lower scores indicating worsening cognitive function. ADAS-Cog11 scores range from 0 to 70 with higher scores indicating worsening cognitive function. FAQ scores range from 0 to 30 with higher scores indicating worsening cognitive function.

Outcome measures

Outcome measures
Measure	CMD (CDR-SB Change >=1) n=162 Participants Subjects who experienced at least a 1 point worsening in CDR-SB score over 18 months	No CMD n=43 Participants Subjects who experienced less than a 1 point worsening in CDR-SB score over 18 months
Mean Change in Cognitive/Functional Assessments CDR-SB	2.22 units on a scale Standard Error 0.215	1.31 units on a scale Standard Error 0.379
Mean Change in Cognitive/Functional Assessments MMSE	-4.89 units on a scale Standard Error 0.377	-2.12 units on a scale Standard Error 0.647
Mean Change in Cognitive/Functional Assessments ADAS-Cog11	6.53 units on a scale Standard Error 0.660	1.97 units on a scale Standard Error 1.181
Mean Change in Cognitive/Functional Assessments FAQ	5.22 units on a scale Standard Error 0.537	2.68 units on a scale Standard Error 0.895

SECONDARY outcome

Timeframe: baseline scan

As measured by Fleiss' Kappa across all scans read. Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. Fleiss' kappa can range from -1 to 1 with 1 indicating perfect agreement between the readers. Read results binarized as τAD++ or non-τAD++.

Outcome measures

Outcome measures
Measure	CMD (CDR-SB Change >=1) n=205 Participants Subjects who experienced at least a 1 point worsening in CDR-SB score over 18 months	No CMD Subjects who experienced less than a 1 point worsening in CDR-SB score over 18 months
Inter-Reader Reliability of Reader Interpretation of Flortaucipir F 18 PET Imaging	0.754 kappa coefficient Interval 0.711 to 0.797	—

Adverse Events

Single Arm, Randomly Sequenced Flortaucipir F18 Scans

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Medical Director

Avid Radiopharmaceuticals, Inc.

Phone: 215-298-0700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60