Ignite Creation Date:
2025-12-25 @ 3:23 AM
Ignite Modification Date:
2026-03-03 @ 7:52 AM
Study NCT ID:
NCT03901105
Status:
COMPLETED
Last Update Posted:
2020-08-28
First Post:
2019-03-28
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Evaluation of Flortaucipir PET Signal and Cognitive Change in Early Alzheimer's Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2020-07-16', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D000544', 'term': 'Alzheimer Disease'}], 'ancestors': [{'id': 'D003704', 'term': 'Dementia'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D024801', 'term': 'Tauopathies'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000591008', 'term': '7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clinicaloperations@avidrp.com', 'phone': '215-298-0700', 'title': 'Medical Director', 'organization': 'Avid Radiopharmaceuticals, Inc.'}, 'certainAgreement': {'restrictionType': 'LTE60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Not applicable, as no new patients received treatment as part of this study.', 'description': 'Adverse event data were not collected in this study.', 'eventGroups': [{'id': 'EG000', 'title': 'Single Arm, Randomly Sequenced Flortaucipir F18 Scans', 'description': 'No study drug was administered for this study. Scans were previously acquired from Study I8D-MC-AZES (NCT02245737, Eli Lilly and Company sponsor) and were read by five independent, blinded readers.\n\nFlortaucipir F18: No study drug was administered for this study.', 'otherNumAtRisk': 0, 'deathsNumAtRisk': 0, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0.5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Risk Ratio for AD Symptom Progression on CDR-SB', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'CMD (CDR-SB Change >=1)', 'description': 'Subjects who experienced at least a 1 point worsening in CDR-SB score over 18 months'}, {'id': 'OG001', 'title': 'No CMD', 'description': 'Subjects who experienced less than a 1 point worsening in CDR-SB score over 18 months'}], 'classes': [{'categories': [{'title': 'tAD++', 'measurements': [{'value': '119', 'groupId': 'OG000'}, {'value': '43', 'groupId': 'OG001'}]}, {'title': 'tAD+', 'measurements': [{'value': '10', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}, {'title': 'tAD-', 'measurements': [{'value': '14', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0313', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Risk Ratio (RR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.36', 'ciLowerLimit': '1.028', 'ciUpperLimit': '1.785', 'pValueComment': 'A priori threshold was two-sided 0.05.', 'estimateComment': 'τAD++ scans represent the numerator for risk, and τAD+/τAD- scans represent the denominator', 'groupDescription': 'Scan results were grouped into τAD++ vs. non-τAD++ (τAD+ and τAD-) for the analysis', 'statisticalMethod': 'log linear model', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for treatment arm (lanabecestat 20 mg, 50 mg, or placebo), baseline age, years of education (categorical), and baseline CDR-SB score.'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Within 18 months of scan', 'description': '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.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Risk Ratio for AD Symptom Progression on Various Clinical Measures', 'denoms': [{'units': 'Participants', 'counts': [{'value': '205', 'groupId': 'OG000'}, {'value': '205', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'CMD Yes', 'description': 'Subjects who experienced CMD for the clinical measure as described above'}, {'id': 'OG001', 'title': 'No CMD', 'description': 'Subjects who did not experience CMD for the clinical measure as described above'}], 'classes': [{'title': 'MMSE', 'denoms': [{'units': 'Participants', 'counts': [{'value': '133', 'groupId': 'OG000'}, {'value': '70', 'groupId': 'OG001'}]}], 'categories': [{'title': 'tAD++', 'measurements': [{'value': '112', 'groupId': 'OG000'}, {'value': '49', 'groupId': 'OG001'}]}, {'title': 'tAD+', 'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}, {'title': 'tAD-', 'measurements': [{'value': '15', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}]}, {'title': 'ADAS-Cog', 'denoms': [{'units': 'Participants', 'counts': [{'value': '112', 'groupId': 'OG000'}, {'value': '87', 'groupId': 'OG001'}]}], 'categories': [{'title': 'tAD++', 'measurements': [{'value': '98', 'groupId': 'OG000'}, {'value': '59', 'groupId': 'OG001'}]}, {'title': 'tAD+', 'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}, {'title': 'tAD-', 'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}]}, {'title': 'FAQ', 'denoms': [{'units': 'Participants', 'counts': [{'value': '134', 'groupId': 'OG000'}, {'value': '66', 'groupId': 'OG001'}]}], 'categories': [{'title': 'tAD++', 'measurements': [{'value': '111', 'groupId': 'OG000'}, {'value': '47', 'groupId': 'OG001'}]}, {'title': 'tAD+', 'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}, {'title': 'tAD-', 'measurements': [{'value': '14', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}]}, {'title': 'CDR Global', 'denoms': [{'units': 'Participants', 'counts': [{'value': '87', 'groupId': 'OG000'}, {'value': '118', 'groupId': 'OG001'}]}], 'categories': [{'title': 'tAD++', 'measurements': [{'value': '71', 'groupId': 'OG000'}, {'value': '91', 'groupId': 'OG001'}]}, {'title': 'tAD+', 'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}, {'title': 'tAD-', 'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '19', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.0833', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Risk Ratio (RR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.35', 'ciLowerLimit': '0.962', 'ciUpperLimit': '1.886', 'pValueComment': 'A priori threshold was two-sided 0.05. No adjustment for multiple comparisons.', 'estimateComment': 'τAD++ scans represent the numerator for risk, and τAD+/τAD- scans represent the denominator', 'groupDescription': 'Risk ratio for MMSE CMD. Scan results were grouped into τAD++ vs. non-τAD++ (τAD+ and τAD-) for the analysis', 'statisticalMethod': 'log linear model', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for treatment arm (lanabecestat 20 mg, 50 mg, or placebo), baseline age, years of education (categorical), and baseline score.'}, {'pValue': '.0141', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Risk Ratio (RR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.77', 'ciLowerLimit': '1.122', 'ciUpperLimit': '2.796', 'pValueComment': 'A priori threshold was two-sided 0.05. No adjustment for multiple comparisons.', 'estimateComment': 'τAD++ scans represent the numerator for risk, and τAD+/τAD- scans represent the denominator', 'groupDescription': 'Risk ratio for ADAS-Cog11 CMD. Scan results were grouped into τAD++ vs. non-τAD++ (τAD+ and τAD-) for the analysis', 'statisticalMethod': 'log linear model', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for treatment arm (lanabecestat 20 mg, 50 mg, or placebo), baseline age, years of education (categorical), and baseline score.'}, {'pValue': '.0639', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Risk Ratio (RR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.32', 'ciLowerLimit': '0.984', 'ciUpperLimit': '1.776', 'pValueComment': 'A priori threshold was two-sided 0.05. No adjustment for multiple comparisons.', 'estimateComment': 'τAD++ scans represent the numerator for risk, and τAD+/τAD- scans represent the denominator', 'groupDescription': 'Risk ratio for FAQ CMD. Scan results were grouped into τAD++ vs. non-τAD++ (τAD+ and τAD-) for the analysis', 'statisticalMethod': 'log linear model', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for treatment arm (lanabecestat 20 mg, 50 mg, or placebo), baseline age, years of education (categorical), and baseline score.'}, {'pValue': '.2814', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Risk Ratio (RR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.28', 'ciLowerLimit': '0.815', 'ciUpperLimit': '2.020', 'pValueComment': 'A priori threshold was two-sided 0.05. No adjustment for multiple comparisons.', 'estimateComment': 'τAD++ scans represent the numerator for risk, and τAD+/τAD- scans represent the denominator', 'groupDescription': 'Risk ratio for CDR Global CMD. Scan results were grouped into τAD++ vs. non-τAD++ (τAD+ and τAD-) for the analysis', 'statisticalMethod': 'log linear model', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for treatment arm (lanabecestat 20 mg, 50 mg, or placebo), baseline age, years of education (categorical), and baseline score.'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Within 18 months of scan', 'description': "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.", 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects were eligible for this analysis; however, row totals reflect subjects for whom clinical measure data was available at baseline and 18 months.'}, {'type': 'SECONDARY', 'title': 'Mean Change in Cognitive/Functional Assessments', 'denoms': [{'units': 'Participants', 'counts': [{'value': '162', 'groupId': 'OG000'}, {'value': '43', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'τAD++ Scan Result', 'description': 'Subjects with a τAD++ scan result'}, {'id': 'OG001', 'title': 'Non-τAD++ Scan Result', 'description': 'Subjects with a Non-τAD++ scan result'}], 'classes': [{'title': 'CDR-SB', 'denoms': [{'units': 'Participants', 'counts': [{'value': '162', 'groupId': 'OG000'}, {'value': '43', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '2.22', 'spread': '0.215', 'groupId': 'OG000'}, {'value': '1.31', 'spread': '0.379', 'groupId': 'OG001'}]}]}, {'title': 'MMSE', 'denoms': [{'units': 'Participants', 'counts': [{'value': '161', 'groupId': 'OG000'}, {'value': '42', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-4.89', 'spread': '0.377', 'groupId': 'OG000'}, {'value': '-2.12', 'spread': '0.647', 'groupId': 'OG001'}]}]}, {'title': 'ADAS-Cog11', 'denoms': [{'units': 'Participants', 'counts': [{'value': '157', 'groupId': 'OG000'}, {'value': '42', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '6.53', 'spread': '0.660', 'groupId': 'OG000'}, {'value': '1.97', 'spread': '1.181', 'groupId': 'OG001'}]}]}, {'title': 'FAQ', 'denoms': [{'units': 'Participants', 'counts': [{'value': '158', 'groupId': 'OG000'}, {'value': '42', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '5.22', 'spread': '0.537', 'groupId': 'OG000'}, {'value': '2.68', 'spread': '0.895', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.0305', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A priori threshold was two-sided 0.05. No adjustment for multiple comparisons.', 'groupDescription': 'MMRM testing the difference between CDR-SB least squares mean changes of tAD++ and Non-tAD++ (tAD+ and tAD-). The unstructured covariance structure (UN) was used.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for baseline clinical score, age, years of education (categorical), and treatment arm (lanabecestat - 20mg or 50mg - or placebo).'}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A priori threshold was two-sided 0.05. No adjustment for multiple comparisons.', 'groupDescription': 'MMRM testing the difference between MMSE least squares mean changes of tAD++ and Non-tAD++ (tAD+ and tAD-). The unstructured covariance structure (UN) was used.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for baseline clinical score, age, years of education (categorical), and treatment arm (lanabecestat - 20mg or 50mg - or placebo).'}, {'pValue': '0.0006', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A priori threshold was two-sided 0.05. No adjustment for multiple comparisons.', 'groupDescription': 'MMRM testing the difference between ADAS-Cog11 least squares mean changes of tAD++ and Non-tAD++ (tAD+ and tAD-). The unstructured covariance structure (UN) was used.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for baseline clinical score, age, years of education (categorical), and treatment arm (lanabecestat - 20mg or 50mg - or placebo).'}, {'pValue': '0.0097', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A priori threshold was two-sided 0.05. No adjustment for multiple comparisons.', 'groupDescription': 'MMRM testing the difference between FAQ least squares mean changes of tAD++ and Non-tAD++ (tAD+ and tAD-). The unstructured covariance structure (UN) was used.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Adjusted for baseline clinical score, age, years of education (categorical), and treatment arm (lanabecestat - 20mg or 50mg - or placebo).'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'baseline and 18 months', 'description': '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.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects were eligible for this analysis; however, row totals reflect subjects for whom clinical measure data was available at baseline and 18 months.'}, {'type': 'SECONDARY', 'title': 'Inter-Reader Reliability of Reader Interpretation of Flortaucipir F 18 PET Imaging', 'denoms': [{'units': 'Participants', 'counts': [{'value': '205', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Subjects/All Readers', 'description': 'All subjects scans included in the study across 5 independent readers'}], 'classes': [{'categories': [{'measurements': [{'value': '0.754', 'groupId': 'OG000', 'lowerLimit': '0.711', 'upperLimit': '0.797'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': "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++.", 'unitOfMeasure': 'kappa coefficient', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'All Subjects', 'description': 'Mild AD and MCI due to AD from the flortaucipir PET scan arm'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '205'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '205'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'recruitmentDetails': '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).', 'preAssignmentDetails': '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.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '205', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Scans', 'description': 'Mild AD and MCI due to AD from the flortaucipir PET scan arm'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '71.0', 'spread': '7.74', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '100', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '105', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '27', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '172', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Flortaucipir PET Scan Result', 'classes': [{'categories': [{'title': 'tAD++', 'measurements': [{'value': '162', 'groupId': 'BG000'}]}, {'title': 'tAD+', 'measurements': [{'value': '15', 'groupId': 'BG000'}]}, {'title': 'tAD-', 'measurements': [{'value': '28', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Majority read result of 5 independent readers. τAD++ (a pattern indicating spread of aggregated tau beyond the posterolateral temporal \\[PLT\\] lobe or occipital lobe); τAD+ (a pattern indicating aggregated tau confined to PLT and/or occipital lobe); or τAD- (inconsistent with an AD pattern).', 'unitOfMeasure': 'Participants'}, {'title': 'Mean CDR-SB', 'classes': [{'categories': [{'measurements': [{'value': '3.69', 'spread': '1.475', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': 'Mean Clinical Dementia Rating - Sum of Boxes Score (CDR-SB). The CDR scale (Berg 1988) examines 6 cognitive functioning domains individually on a scale of 0 to 3. CDR Sum of Boxes is generated by summing the total score across domains. Scores range from 0 to 18, with higher scores indicating higher levels of cognitive impairment.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-03-12', 'size': 310249, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-06-27T14:37', 'hasProtocol': True}, {'date': '2019-04-16', 'size': 370119, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-06-27T14:37', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'PET scans were obtained in an open-label fashion.'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Physician PET scan readers are participants, blinded to demographic and clinical data from the source PET scans.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 205}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-03-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-08', 'dispFirstSubmitDate': '2020-01-22', 'completionDateStruct': {'date': '2019-04-28', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-08-21', 'studyFirstSubmitDate': '2019-03-28', 'dispFirstSubmitQcDate': '2020-08-21', 'resultsFirstSubmitDate': '2020-06-27', 'studyFirstSubmitQcDate': '2019-04-01', 'dispFirstPostDateStruct': {'date': '2020-08-28', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2020-08-28', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-08-21', 'studyFirstPostDateStruct': {'date': '2019-04-03', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2020-08-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-04-28', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Risk Ratio for AD Symptom Progression on CDR-SB', 'timeFrame': 'Within 18 months of scan', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Risk Ratio for AD Symptom Progression on Various Clinical Measures', 'timeFrame': 'Within 18 months of scan', 'description': "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."}, {'measure': 'Mean Change in Cognitive/Functional Assessments', 'timeFrame': 'baseline and 18 months', 'description': '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.'}, {'measure': 'Inter-Reader Reliability of Reader Interpretation of Flortaucipir F 18 PET Imaging', 'timeFrame': 'baseline scan', 'description': "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++."}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Alzheimer Disease']}, 'referencesModule': {'references': [{'pmid': '33587110', 'type': 'DERIVED', 'citation': 'Lu M, Pontecorvo MJ, Devous MD Sr, Arora AK, Galante N, McGeehan A, Devadanam C, Salloway SP, Doraiswamy PM, Curtis C, Truocchio SP, Flitter M, Locascio T, Devine M, Zimmer JA, Fleisher AS, Mintun MA; AVID Collaborators. Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. JAMA Neurol. 2021 Apr 1;78(4):445-453. doi: 10.1001/jamaneurol.2020.5505.'}]}, 'descriptionModule': {'briefSummary': 'This study will evaluate whether visual interpretation of flortaucipir-PET (positron emission tomography) scans, examining patterns of tracer uptake at baseline, can predict the rate of clinically-meaningful cognitive decline due to AD after 18 months. All scans are acquired from cohorts of a previously completed study, I8D-MC-AZES (NCT02245737, lanabecestat, Eli Lilly and Company sponsor).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '55 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Scan Reader Criteria (5 total readers):\n\n* Board-certified in radiology or nuclear medicine\n* Professional experience interpreting PET scans\n\nScan Criteria (205 total scans):\n\n* Former enrollment in AZES Study\n* Flortaucipir scan at baseline\n* clinical dementia rating - sum of boxes (CDR-SB) assessment at 18 months\n\nScan Study Population (AZES Study):\n\n* 55 to 85 years\n* MCI due to AD or probable AD by National Institute on Aging-Alzheimer's Association criteria (Albert 2011\n* mini-mental status exam (MMSE) of 20 to 30 inclusive\n* CDR global score of 0.5 (MCI), or 0.5 or 1 (AD) with a memory box score ≥ 0.5, and a score of ≤85 on the Delayed Memory Index of the Repeatable Battery for the Assessment of Neuropsychological Status.\n* Amyloid positive status confirmed by florbetapir PET or lumbar puncture"}, 'identificationModule': {'nctId': 'NCT03901105', 'briefTitle': "Evaluation of Flortaucipir PET Signal and Cognitive Change in Early Alzheimer's Disease", 'organization': {'class': 'INDUSTRY', 'fullName': 'Avid Radiopharmaceuticals'}, 'officialTitle': "Evaluation of the Relationship Between Baseline Flortaucipir PET Signal and Cognitive Change in Subjects With Early Alzheimer's Disease Participating in the I8D-MC-AZES Protocol Addendum D5010C00009 (2.1) (Tau Imaging)", 'orgStudyIdInfo': {'id': '18F-AV-1451-PX01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Flortaucipir PET Scan', 'description': 'No study drug will be administered. Scans previously acquired from Study I8D-MC-AZES (NCT02245737, Eli Lilly and Company sponsor) will be read by independent, blinded readers.', 'interventionNames': ['Drug: flortaucipir F18', 'Procedure: Brain PET Scan']}], 'interventions': [{'name': 'flortaucipir F18', 'type': 'DRUG', 'otherNames': ['18F-AV-1451', '[F-18]T807', 'LY3191748'], 'description': 'No study drug will be administered. Scans previously acquired from Study I8D-MC-AZES (NCT02245737, Eli Lilly and Company sponsor) at baseline will be read by independent, blinded readers. IV injection, 240 megabecquerel (MBq) (6.5 mCi), single dose in AZES', 'armGroupLabels': ['Flortaucipir PET Scan']}, {'name': 'Brain PET Scan', 'type': 'PROCEDURE', 'description': 'positron emission tomography (PET) scan of the brain', 'armGroupLabels': ['Flortaucipir PET Scan']}]}, 'contactsLocationsModule': {'locations': [{'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'American College of Radiology', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}], 'overallOfficials': [{'name': 'Study Director', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Avid Radiopharmaceuticals'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Avid Radiopharmaceuticals', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}